Page last updated: 2024-12-05

leflunomide

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Description

Leflunomide is an antirheumatic drug used to treat rheumatoid arthritis. It is a prodrug that is converted to its active metabolite, A77 1726, which inhibits dihydroorotate dehydrogenase, an enzyme involved in pyrimidine synthesis. This inhibition leads to a decrease in the production of pyrimidines, which are essential for DNA and RNA synthesis, ultimately suppressing immune responses. Leflunomide's mechanism of action has been extensively studied, and its importance lies in its ability to provide long-term disease modification in patients with rheumatoid arthritis. The drug has been shown to reduce joint swelling and damage, and improve physical function. Continued research is conducted to investigate its potential applications in other autoimmune diseases and to explore further its effects on various cellular processes.'

Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID3899
CHEMBL ID960
CHEBI ID6402
SCHEMBL ID5057
MeSH IDM0132172

Synonyms (212)

Synonym
BIDD:PXR0189
AC-6796
MLS001076267
bdbm50054601
HMS3268D12
AB00052389-18
BRD-K78692225-001-03-9
KBIO1_000916
DIVK1C_000916
su-101
repso
leflunomidum
5-methyl-n-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
leflunomida
CHEBI:6402 ,
rs-34821
isoxazole-4-carboxamide, 5-methyl-n-[4-(trifluoromethyl)phenyl]-
hwa 486
nsc677411
nsc-677411
EU-0100649
leflunomide, immunosuppressant
hsdb 7289
su 101 (pharmaceutical)
leflunomida [inn-spanish]
su101
SPECTRUM_000322
4-isoxazolecarboxamide, 5-methyl-n-(4-(trifluoromethyl)phenyl)-
leflunomidum [inn-latin]
5-methyl-n-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide
n-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide
alpha,alpha,alpha-trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidide
n-(4-trifluoromethyphenyl)-5-methylisoxazole-4-carboxamide
hwa-486
5-methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide
PRESTWICK_87
lefunamide
NCGC00015610-02
lopac-l-5025
cas-75706-12-6
NCGC00015610-01
BSPBIO_000844
LOPAC0_000649
5-methyl-n-[4-(trifluoromethyl)phenyl]isoxazole-4-carboxamide
4-isoxazolecarboxamide, 5-methyl-n-(4-(trifluoromethyl)phenyl
su 101
arava
IDI1_000916
SPECTRUM5_000850
PRESTWICK2_000772
MLS-0003109.0001
AB00052389
C07905
75706-12-6
leflunomide
DB01097
leflunomide (jan/usp/inn)
D00749
arava (tn)
NCGC00022625-05
NCGC00022625-06
NCGC00022625-07
smr000058209
MLS000069648 ,
KBIOSS_000802
KBIO2_000802
KBIO2_003370
KBIO2_005938
NINDS_000916
SPBIO_002783
PRESTWICK1_000772
PRESTWICK0_000772
SPECTRUM1503927
PRESTWICK3_000772
BPBIO1_000930
NCGC00022625-04
NCGC00022625-08
NCGC00015610-03
NCGC00022625-03
NCGC00015610-07
5-methylisoxazole-4-(4-trifluoromethylcarboxanilide)
L 5025 ,
HMS2090O12
NCGC00015610-12
AKOS000265193
leflunomide winthrop
nsc-759864
CHEMBL960 ,
leflunomide medac
sulol
l04aa13
leflunomide teva
leflunomide ratiopharm
HMS502N18
HMS1922M06
HMS1570K06
5-methyl-n-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamide;leflunomide
A9622
HMS3262A19
HMS2097K06
4-isoxazolecarboxamide, 5-methyl-n-[4-(trifluoromethyl)phenyl]-
unii-g162gk9u4w
g162gk9u4w ,
leflunomide [usan:usp:inn:ban]
nsc 759864
nsc 677411
NCGC00255370-01
tox21_301873
dtxsid9023201 ,
dtxcid103201
pharmakon1600-01503927
nsc759864
tox21_110182
L0250
CCG-204736
HMS2235C07
NCGC00015610-10
NCGC00015610-05
NCGC00015610-09
NCGC00015610-08
NCGC00015610-06
NCGC00015610-04
NCGC00015610-11
NCGC00015610-14
NCGC00015610-13
BCP9000846
lefunomide [inn-spanish]
FT-0621959
NCGC00015610-18
LP00649
leflunomide [inn]
leflunomide [usp monograph]
n-(4-(trifluoromethyl)phenyl) 5 methylisoxazole-4-carboxamide
leflunomide [hsdb]
leflunomide [ema epar]
leflunomide [jan]
leflunomide [who-dd]
leflunomide [vandf]
leflunomide [orange book]
leflunomide [usan]
leflunomide [usp-rs]
leflunomide [ep monograph]
leflunomide [ep impurity]
leflunomide [mi]
leflunomide [mart.]
S1247
gtpl6825
HMS3371F21
arabloc
DL-433
CS-1781
HY-B0083
SCHEMBL5057
tox21_110182_1
NCGC00015610-17
KS-1076
AB00052389-17
tox21_500649
NCGC00261334-01
5-methyl-4-(4-trifluoromethyl-phenyl)aminocarbonylisoxazole
n-(4-trifluoromethylphenyl)-5-methylisoxa-zole-4-carboxamide
5-methyl-4-(4-trifluoromethylphenyl)aminocarbonylisoxazole
5-methylisoxazole-4-carboxylic acid (4-trifluoromethyl)-anilide
n-(4-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide
Q-201289
5-methyl-n-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide
STL426823
5-methyl-n-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamide
AB00052389_21
AB00052389_19
OPERA_ID_1709
mfcd00867593
hwa486
sr-01000000191
SR-01000000191-2
leflunomide, united states pharmacopeia (usp) reference standard
HMS3654F07
leflunomide, european pharmacopoeia (ep) reference standard
leflunomide for peak identification, european pharmacopoeia (ep) reference standard
leflunomide, pharmaceutical secondary standard; certified reference material
SR-01000000191-7
SR-01000000191-4
HMS3714K06
SW196399-3
hwa486; rs-34821; su101;hwa 486; rs 34821; su 101
BCP22241
HMS3678N21
Q248550
HMS3414P03
BRD-K78692225-001-11-2
SB17287
HMS3673M17
HMS3865I13
SDCCGSBI-0050629.P003
NCGC00015610-30
5-methyl-n-[4-(trifluoromethyl)-phenyl]isoxazole-4-carboxamide
leflunomide 100 microg/ml in acetonitrile
leflunomide for peak identification
BM164612
EN300-119495
Z228668542
leflunomide (ep monograph)
leflunomide (mart.)
5-methyl-n-
5-methyl-n-(4-(trifluoromethyl)phenyl)-1,2-oxazole-4-carboxamide
5-methylisoxazole-4-carboxylic acid trifluoromethylanilide
leflunomidum (inn-latin)
leflunomide (usp monograph)
leflunomide (ep impurity)
leflunomide (usp-rs)
leflunomida (inn-spanish)
leflunomide (usan:usp:inn:ban)

Research Excerpts

Overview

Leflunomide is a classic disease-modifying anti-rheumatic drug that is widely used to treat autoimmune diseases. It is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes. Lefl Unomide (LEF) is an anti-inflammatory drug primarily used for treating rheumatoid arthritis (RA)

ExcerptReferenceRelevance
"Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis."( Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up.
Bao, C; Dai, L; Dai, M; Fu, Q; He, L; Li, Z; Lu, L; Sun, L; Wang, S; Wu, C; Xu, J; Zhu, X, 2022
)
2.89
"Leflunomide is a commonly used treatment for rheumatoid arthritis. "( Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?
Aicha, BT; Hana, S; Ines, M; Issam, S; Kawther, BA; Leila, A; Leila, M; Lobna, BA; Mouna, BS; Olfa, S; Rawdha, T; Selma, B; Takoua, BB, 2023
)
2.57
"Leflunomide is a classic disease-modifying anti-rheumatic drug that is widely used to treat autoimmune diseases. "( Leflunomide: Traditional immunosuppressant with concurrent antiviral effects.
Chen, Y; He, C; Li, M; Liu, S; Wang, L; Wu, D; Yang, Y; Zeng, X; Zhang, F; Zheng, K, 2023
)
3.8
"Leflunomide is an immunosuppressive drug indicated for the treatment of rheumatoid arthritis (RA). "( Development of a population pharmacokinetic model and optimal dosing regimen of leflunomide in Korean population.
Chae, D; Park, K; Shin, Y, 2023
)
2.58
"Leflunomide is a commonly used disease modifying antirheumatic agent. "( Leflunomide exposure through second trimester of pregnancy: A case report.
Alothman, R; Amiri, N; Lepik, C; Waterman, E; Yeung, J, 2023
)
3.8
"Leflunomide (LFD) is an Aryl hydrocarbon receptor (AhR) agonist and immunomodulatory drug with several side effects. "( Encapsulation of Leflunomide (LFD) in a novel niosomal formulation facilitated its delivery to THP-1 monocytic cells and enhanced Aryl hydrocarbon receptor (AhR) nuclear translocation and activation.
Arabi, MS; Hasani, M; Khodabakhshi, B; Mohammadi, S; Sani, NA; Yazdani, Y, 2019
)
2.3
"Leflunomide is a disease modifying anti-rheumatic drug (DMARD) beneficial in refractory cases of rheumatoid arthritis. "( Leflunomide-induced liver injury in mice: Involvement of TLR4 mediated activation of PI3K/mTOR/NFκB pathway.
El-Ghaiesh, SH; Elshaer, RE; Elsherbiny, NM; Nosseir, N; Tawfik, MK; Toraih, EA; Zaitone, SA, 2019
)
3.4
"Leflunomide (LEF) is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes."( Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis.
Feng, S; He, Z; Xu, S; Yi, J, 2019
)
1.55
"Leflunomide is a commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). "( Precision Medicine With Leflunomide: Consideration of the DHODH Haplotype and Plasma Teriflunomide Concentration and Modification of Outcomes in Patients With Rheumatoid Arthritis.
Cleland, LG; Hill, C; Hopkins, AM; King, C; Lee, A; McWilliams, L; Metcalf, R; Proudman, SM; Spargo, L; Wechalekar, MD; Wiese, MD, 2021
)
2.37
"Leflunomide is an anti-inflammatory drug primarily used for treating rheumatoid arthritis (RA)."( A77 1726, the active metabolite of the anti-rheumatoid arthritis drug leflunomide, inhibits influenza A virus replication in vitro and in vivo by inhibiting the activity of Janus kinases.
Hu, J; Liu, X; Peng, D; Prinz, RA; Sun, J; Wang, C; Wang, J; Xu, X, 2020
)
1.51
"Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in cHP patients. "( Use of leflunomide in patients with chronic hypersensitivity pneumonitis.
Culver, DA; Li, M; Noh, S; Pande, A; Sahoo, D; Wang, X; Yadav, R, 2020
)
2.46
"Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. "( Leflunomide monotherapy versus combination therapy with conventional synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis: a retrospective study.
Deng, D; Li, M; Li, S; Tian, L; Wang, T; Wu, J; Yang, J; Zeng, F; Zhou, J; Zou, J, 2020
)
3.44
"Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). "( Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis.
Dziedziejko, V; Malinowski, D; Paradowska-Gorycka, A; Pawlik, A; Safranow, K; Łączna, M, 2021
)
2.29
"Leflunomide is a prodrug that is metabolized to the active metabolite, teriflunomide (A77 1726), to inhibit the enzyme dihydroorotate dehydrogenase and decrease the synthesis of pyrimidine nucleotides for DNA and RNA synthesis. "( LC-MS/MS Method for the Quantification of the Leflunomide Metabolite, Teriflunomide, in Human Serum/Plasma.
Johnson-Davis, KL; Rockwood, AL; Rule, GS, 2019
)
2.21
"Leflunomide is a disease-modifying anti-rheumatic drug (DMARD) used in the management of rheumatoid arthritis (RA) and psoriatic arthritis. "( Reversible alopecia areata: a little known side effect of leflunomide.
Cusnir, I; Hall, J; Koller, G; Ye, C, 2019
)
2.2
"Leflunomide is an effective and well-tolerated treatment for PsA, and would be a safe and convenient option."( Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysis.
Dai, Q; Xu, L; Yu, X, 2019
)
2.27
"Leflunomide is an immunosuppressive drug with antiviral activity and has been used in treating BKV-associated nephropathy after renal transplantation."( Efficacy and safety of leflunomide for the treatment of BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients.
Chen, XC; He, C; Huang, R; Li, JJ; Liu, T; Meng, WT, 2013
)
1.42
"Leflunomide is a prodrug which is rapidly converted following oral administration and absorption to an active metabolite with anti-proliferative effects (A77 1726/teriflunomide). "( Safety evaluation of leflunomide in rheumatoid arthritis.
Conaghan, PG; Keen, HI; Tett, SE, 2013
)
2.15
"Leflunomide is a relatively safe drug, with proven efficacy in RA management. "( Safety evaluation of leflunomide in rheumatoid arthritis.
Conaghan, PG; Keen, HI; Tett, SE, 2013
)
2.15
"Leflunomide (LFN) is a disease-modifying antirheumatic drug approved for the treatment of rheumatoid arthritis, and its active metabolite teriflunomide has been identified as a potential anticancer drug."( Leflunomide suppresses growth in human medullary thyroid cancer cells.
Alhefdhi, A; Burke, JF; Chen, H; Kunnimalaiyaan, M; Redlich, A, 2013
)
2.55
"Leflunomide is a disease-modifying antirheumatic drug. "( Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean healthy volunteers.
Kim, EY; Kim, HS; Lim, YJ; Moon, BS; Oh, M; Shim, EJ; Shin, JG; Shon, JH; Song, GS, 2013
)
2.09
"Leflunomide (LFN) is a disease modifying anti-rheumatic drugs (DMARDs) which acts by inhibiting the synthesis of pyrimidines."( Use of leflunomide plus TNF-α inhibitors in rheumatoid arthritis.
Murdaca, G; Puppo, F; Spanò, F, 2013
)
1.57
"Leflunomide is a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). "( Comparison of two molecular scaffolds, 5-methylisoxazole-3-carboxamide and 5-methylisoxazole-4-carboxamide.
Chen, B; Huang, WH; Lee, AR; Palfey, B; Shaw, J; Song, Y; Zhang, Y, 2014
)
1.85
"Leflunomide (LEF) is an isoxazole derivative used as disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA). "( [Acute interstitial pneumonia in patient with rheumatoid arthritis treated with leflunomide].
Bartosiewicz, M; Bartoszuk, I; Jakubowska, L; Kuś, J; Siemion-Szcześniak, I; Wesołowski, S, 2014
)
2.07
"Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis."( Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.
Abdel-Naim, AB; Al-Abbasi, FA; Al-Abd, AM; El-Eraky, WI; Khalifa, AE; Nagy, AA; Nofal, SM; Williams, RO, 2014
)
1.36
"Leflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid arthritis. "( Inhibition of p70 S6 kinase (S6K1) activity by A77 1726 and its effect on cell proliferation and cell cycle progress.
Bogachkov, Y; Doscas, ME; Kaufman, H; Li, Y; Rao, GS; Ruby, C; Usha, L; Wang, Y; Williams, JW; Williamson, AJ; Xiao, F; Xu, X; Zhou, J, 2014
)
1.85
"Leflunomide is an immunosuppressant drug used in rheumatoid arthritis and psoriatic arthritis. "( [Pleuro-pericarditis developed under a leflunomide therapy].
Figueredo, M; Ribière, J; Tarhini, A; Vandenbos, F, 2015
)
2.13
"Leflunomide is a disease-modifying anti-rheumatic drug that is used in patients with rheumatoid arthritis (RA), who do not respond well to standard RA treatment. "( Leflunomide-induced acute interstitial pneumonia in a patient treated for rheumatoid arthritis.
Chazan, R; Karwat, K; Langfort, R; Maskey-Warzęchowska, M; Szczepankiewicz, B; Szołkowska, M, 2015
)
3.3
"Leflunomide (LEF) is a disease-modifying anti-rheumatic drug used for treating rheumatoid arthritis (RA). "( Genetic polymorphisms in metabolic pathways of leflunomide in the treatment of rheumatoid arthritis.
Dosedel, M; Nekvindova, J; Pavek, P; Soukup, T; Toms, J; Vlcek, J,
)
1.83
"Leflunomide (LEF) is an immune modulator used most commonly for rheumatoid arthritis (RA). "( Leflunomide: an immune modulating drug that may have a role in controlling secondary infections with review of its mechanisms of action.
Germain, M; Smith, KJ, 2015
)
3.3
"Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and immunosuppressive activity used for the treatment of psoriatic and rheumatoid arthritis. "( On the interactions of leflunomide and teriflunomide within receptor cavity--NMR studies and energy calculations.
Bernard, MK; Czaja, K; Drabińska, B; Jodłowska, E; Kujawski, J, 2015
)
2.17
"Leflunomide is a Food and Drug Administration-approved drug in humans that is known to have AhR agonist activity in vitro."( Leflunomide Induces Pulmonary and Hepatic CYP1A Enzymes via Aryl Hydrocarbon Receptor.
Jiang, W; Moorthy, B; Paramahamsa, M; Patel, A; Shivanna, B; Wang, L; Zhang, S, 2015
)
2.58
"Leflunomide is a DMARD that has a prolonged half-life due to enterohepatic recirculation."( Use of a Cholestyramine Washout in a Patient With Septic Shock on Leflunomide Therapy: A Case Report and Review of the Literature.
Fraser, R; Kiser, TH; Kurche, J; Lara, A; Laub, M; Reynolds, PM, 2016
)
1.39
"Leflunomide is an immunosuppressive drug reported as effective in several immune-mediated diseases."( Efficacy of leflunomide for treatment of refractory inflammatory colorectal polyps in 15 Miniature Dachshunds.
Eguchi, N; Fukushima, K; Igarashi, H; Kanemoto, H; Nakashima, K; Ohmi, A; Ohno, K; Takahashi, M; Tsujimoto, H, 2016
)
1.53
"Leflunomide is an effective drug used in the treatment of rheumatoid arthritis. "( Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study.
Chen, P; Deng, J; Feng, H; Liu, W; Luo, Y; Ou, C; Qiu, L, 2016
)
3.32
"Leflunomide is a prodrug used primarily for treatment of rheumatoid arthritis. "( Quantitation of Teriflunomide in Human Serum/Plasma Across a 40,000-Fold Concentration Range by LC/MS/MS.
Johnson-Davis, KL; Rockwood, AL; Rule, GS, 2016
)
1.88
"Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. "( The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis.
Cao, H; Chen, Z; Lin, J; Liu, L; Rao, Y; Yang, H; Zhang, X, 2015
)
2.16
"Leflunomide is an immunosuppressive agent marketed as a disease-modifying antirheumatic drug. "( Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity.
Cao, YY; Chen, C; Lin, YF; Luan, Y; Ma, LL; Ni, X; Pan, GY; Wang, J; Wang, L; Wu, ZT; Zhang, XF, 2016
)
2.1
"Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA."( Diffuse alveolar damage in a patient with rheumatoid arthritis under prolonged leflunomide treatment: A Case Report and Literature Review.
Chung, KP; Huang, HN; Keng, LT; Lin, MW, 2016
)
1.38
"Leflunomide is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. "( An unusual case report of gingival overgrowth associated with the use of leflunomide.
Guzelkucuk, U; Yavuz, F,
)
1.81
"Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. "( The active metabolite of leflunomide, A77 1726, attenuates inflammatory arthritis in mice with spontaneous arthritis via induction of heme oxygenase-1.
Cho, ML; Jhun, JY; Kim, EK; Lee, HJ; Lee, WS; Min, JK; Moon, SJ; Park, SH, 2017
)
2.2
"Leflunomide is an immunosuppressive drug with in vitro and initial observational evidence of antiviral activity against BK virus (BKV), a pathogen that causes opportunistic infection upon reactivation in renal transplant recipients. "( Clinical Pharmacokinetic Monitoring of Leflunomide in Renal Transplant Recipients with BK Virus Reactivation: A Review of the Literature.
Ensom, MHH; Leung, M; Ng, JCY; Wright, AJ, 2017
)
2.17
"Leflunomide seems to be an effective treatment for RA, alternative to current therapies."( The changes in serum chemokines following leflunomide therapy in patients with rheumatoid arthritis.
Chwiecko, J; Kita, J; Klimiuk, PA; Sierakowski, S, 2009
)
1.34
"Leflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. "( Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis.
Baaj, M; El Haouri, M; Hadri, L; Hassikou, H; Safi, S; Tabache, F, 2008
)
3.23
"Leflunomide is a drug used in rheumatoid arthritis with teratogenic and fetotoxic effects. "( A pair of twins born after maternal exposure to leflunomide.
Heine, K; Poets, CF, 2008
)
2.04
"Leflunomide is an immunosuppressant drug displaying teratogenicity in mice, rats, and rabbits. "( Inhibiting the teratogenicity of the immunosuppressant leflunomide in mice by supplementation of exogenous uridine.
Fukushima, R; Hirashiba, M; Hishikawa, A; Kanamori, S; Kaneto, M; Kitagawa, H; Muranaka, R, 2009
)
2.04
"Leflunomide is an isoxazole derivative structurally and functionally unrelated to other known immunomodulatory drugs. "( The effect of exon (19C>A) dihydroorotate dehydrogenase gene polymorphism on rheumatoid arthritis treatment with leflunomide.
Drozdzik, M; Dziedziejko, V; Herczynska, M; Kurzawski, M; Pawlik, A; Safranow, K, 2009
)
2.01
"Leflunomide is an isoxazole derivative that is structurally and functionally unrelated to other known immunomodulatory drugs. "( IL-1beta, IL-6, and TNF gene polymorphisms do not affect the treatment outcome of rheumatoid arthritis patients with leflunomide.
Droździk, M; Dziedziejko, V; Herczyńska, M; Juzyszyn, Z; Kurzawski, M; Pawlik, A; Safranow, K,
)
1.78
"Leflunomide is a useful and well tolerated DMARD for the treatment of RA and psoriatic arthritis in the elderly. "( Leflunomide treatment in elderly patients with rheumatoid or psoriatic arthritis: retrospective analysis of safety and adherence to treatment.
Alivernini, S; Ferraccioli, G; Mazzotta, D; Zoli, A, 2009
)
3.24
"Leflunomide is a disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). "( Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis.
Bohanec Grabar, P; Dolzan, V; Grabnar, I; Logar, D; Mrhar, A; Peterlin Masic, L; Rozman, B; Suput, D; Tomsic, M; Trdan, T, 2009
)
1.99
"Leflunomide is an immunomodulator drug with applications in the management of arthritis rheumatoid. "( Synthesis and immunomodulation of human lymphocyte proliferation and cytokine (interferon-gamma) production of four novel malonitrilamides.
Alahyari, M; Hadizadeh, F; Jaafari, MR; Moallem, SA; Rameshrad, M; Samiei, A; Shahab, M, 2009
)
1.8
"Leflunomide is a novel immunomodulating drug that is also a potent inhibitor of NF-kappaB activation."( Leflunomide: is a new oral agent in treatment of acute pancreatitis?
Kaptanoglu, B; Kutluana, U; Nart, D; Oruc, N; Ozutemiz, O; Yonetci, N, 2010
)
2.52
"Leflunomide is a beneficial agent in the severe form of acute pancreatitis in rats and should be considered as a potential agent for treatment of acute pancreatitis."( Leflunomide: is a new oral agent in treatment of acute pancreatitis?
Kaptanoglu, B; Kutluana, U; Nart, D; Oruc, N; Ozutemiz, O; Yonetci, N, 2010
)
3.25
"Leflunomide is an effective DMARD that sustains a clinical and radiological response comparable to sulfasalazine and methotrexate."( Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing.
Alcorn, N; Madhok, R; Saunders, S, 2009
)
1.37
"Leflunomide is a disease-modifying antirheumatic drug (DMARD) with comparable efficacy to methotrexate in the treatment of rheumatoid arthritis. "( Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study.
Kim, KA; Lee, GH; Lee, YH; Park, JY; Park, SW; Ryu, JH, 2010
)
2.05
"Leflunomide (LMF) is an immunemodulatory drug used in the therapy of Rheumatoid Arthritis (RA). "( Pregnancy course and neonatal outcome after exposure to leflunomide--2 cases report and review of literature.
Banas, T; Batko, B; Górnisiewicz, T; Hajdyla-Banaś, I; Pityńska-Korab, E; Rydz-Stryszowska, I; Skura, A, 2009
)
2.04
"Leflunomide (LEF) is a DMARD with anti-inflammatory and immunomodulatory properties."( Influence of long-term leflunomide treatment on serum amyloid concentration in rheumatoid arthritis patients.
Dryglewska, M; Majdan, M; Targońska-Stępniak, B,
)
1.16
"Leflunomide (LEF) is an immunomodulator derived from isoxazole It is an approved drug in the rheumatoid arthritis (RA). "( [Peripheral neuropathy caused by leflunomide. A case reported with a brief review].
Antonio-Valdiviezo, A; Martínez-Torres, J; Peña-Santos, G,
)
1.86
"Leflunomide is a disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). "( Leflunomide in Pakistani patients with rheumatoid arthritis: prospective study in daily rheumatology practice.
Ahmad, NM; Farman, S; Ghafoor, E; Hameed, R; Saeed, MA; Umair, M, 2011
)
3.25
"Leflunomide is a viable alternative agent for pulmonary and extrapulmonary sarcoidosis."( Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis.
Bandyopadhyay, D; Chapman, JT; Culver, DA; Lazar, CA; Parambil, JG; Pearson, K; Sahoo, DH; Xu, M, 2011
)
1.38
"Leflunomide is a synthetic isoxazole-derivative drug that possesses both immunosuppressive and antiviral properties. "( Leflunomide in renal transplantation.
Chon, WJ; Josephson, MA, 2011
)
3.25
"Leflunomide is a disease-modifying antirheumatic drug that is commonly used to treat rheumatoid arthritis."( Inhibiting effects of Leflunomide metabolite on overexpression of CD147, MMP-2 and MMP-9 in PMA differentiated THP-1 cells.
Gu, JR; Huang, JL; Wang, MX; Wu, SY; Xie, XJ; Zhu, S, 2011
)
1.41
"Leflunomide is an oral disease-modifying antirheumatic drug administered to patients with rheumatoid and psoriatic arthritis. "( Leflunomide in dermatology.
Boyd, AS, 2012
)
3.26
"Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. "( Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration.
Chatzidionysiou, K; Gabay, C; Gomez-Reino, J; Hetland, ML; Kvien, TK; Lie, E; Lukina, G; Nasonov, E; Nordström, DC; Pavelka, K; Tarp, U; Tomsic, M; van Riel, PL; van Vollenhoven, RF, 2012
)
2.04
"Leflunomide (LEF) is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA) and the action of which may be modified by sex hormones. "( Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide.
Chlubek, D; Dziedziejko, V; Kurzawski, M; Ossowski, A; Parafiniuk, M; Pawlik, A; Piatek, J; Safranow, K, 2012
)
2.02
"Leflunomide is an antirheumatic drug whose administration to HIV-1-infected persons effectively decreases T-cell turnover and activation."( Ritonavir-induced lipoatrophy and dyslipidaemia is reversed by the anti-inflammatory drug leflunomide in a PPAR-γ-dependent manner.
Baldelli, F; Basile, F; Cipriani, S; D'Amore, C; Fiorucci, S; Francisci, D; Mencarelli, A; Renga, B; Schiaroli, E, 2012
)
1.32
"Leflunomide is an immunomodulating drug that has been used clinically for the treatment of rheumatoid arthritis and other immune system disorders. "( Synthesis and immunomodulation of human lymphocyte proliferation and cytokine (interferon-γ) production of four novel leflunomide analogues.
Allahyari, M; Farimani, ES; Hadizadeh, F; Moalem, SA; Rameshrad, M, 2012
)
2.03
"Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent."( Conversion from tacrolimus/mycophenolic acid to tacrolimus/leflunomide to treat cutaneous warts in a series of four pediatric renal allograft recipients.
Alexander, SR; Chaudhuri, A; Chen, SF; Concepcion, W; Grimm, P; McClellan, RB; Nguyen, L, 2012
)
1.34
"Leflunomide is a new immunosuppressive medicine that has been effectively used in the therapy of rheumatoid arthritis and subsequently used with success in animal models and patients with systemic lupus erythematosus (SLE). "( Leflunomide: friend or foe for systemic lupus erythematosus?
Huang, Q; Wu, GC; Wu, H; Xu, XD, 2013
)
3.28
"Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. "( Association of DHODH haplotype variants and response to leflunomide treatment in rheumatoid arthritis.
Cleland, LG; James, M; O'Doherty, C; Proudman, SM; Schnabl, M; Spargo, L; Wiese, MD, 2012
)
2.07
"Leflunomide is an effective and well-tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease."( Leflunomide in psoriatic arthritis: results from a large European prospective observational study.
Behrens, F; Burkhardt, H; Finkenwirth, C; Pavelka, K; Šipek-Dolnicar, A; Štolfa, J; Thaçi, D, 2013
)
3.28
"Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. "( Prospective, pilot, open-label, short-term study of conversion to leflunomide reverses chronic renal allograft dysfunction.
Brennan, DC; Hardinger, KL; Jendrisak, MD; Lowell, JA; Miller, BW; Schnitzler, MA; Shenoy, S; Wang, CD, 2002
)
1.99
"Leflunomide(Arava) is a novel immunomodulatory drug, the primary action of which is inhibition of de-novo pyrimidine synthesis by selective inhibition of dihydro-orotate dehydrogenase. "( [Efficacy of leflunomide].
Hirohata, S, 2002
)
2.13
"Leflunomide (Arava) is an immunomodulator, recently introduced for systemic treatment of rheumatoid arthritis. "( [Lichenoid drug reaction to leflunomide].
Canonne-Courivaud, D; Carpentier, O; Dejobert, Y; Delaporte, E; Hachulla, E, 2003
)
2.06
"Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. "( Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide.
Barta, U; Bauer, HI; Elsner, P; Fischer, TW; Graefe, T, 2003
)
1.99
"Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. "( Additive effects of leflunomide and tacrolimus in prevention of islet xenograft rejection.
Ekberg, H; Qi, Z; Shan, S; Wu, D; Zhang, L, 2004
)
2.09
"Leflunomide is a novel disease modifying antirheumatic drug (DMARD). "( Leflunomide for the treatment of rheumatoid arthritis in clinical practice: incidence and severity of hepatotoxicity.
Brouwers, JR; Houtman, NM; Jansen, TL; Spoelstra, P; van Roon, EN, 2004
)
3.21
"Leflunomide (Arava) is a cytotoxic drug which has been used as a single agent or in combination with methotrexate for the treatment of rheumatoid arthritis. "( Leflunomide for chronic sarcoidosis.
Baughman, RP; Lower, EE, 2004
)
3.21
"Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. "( The active metabolite of leflunomide, A77 1726, increases the production of IL-1 receptor antagonist in human synovial fibroblasts and articular chondrocytes.
Burger, D; Dayer, JM; Gabay, C; Guerne, PA; Magne, D; Mezin, F; Palmer, G, 2004
)
2.07
"Leflunomide is a low-molecular weight, synthetic, oral agent specifically developed for immunosuppression. "( Leflunomide.
Cannon, GW; Kremer, JM, 2004
)
3.21
"Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies."( Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.
Behrens, F; Falk, FG; Gladman, D; Jones, P; Kaltwasser, JP; Mease, P; Nash, P; Rosen, CF; Wollenhaupt, J, 2004
)
2.08
"Leflunomide is an agent that affects the inflammatory process, particularly in RA."( Leflunomide in the treatment of rheumatoid arthritis.
Li, EK; Tam, LS; Tomlinson, B, 2004
)
2.49
"Leflunomide is a pyrimidine de novo synthesis-inhibiting immunosuppressant exhibiting an extremely long in vivo half life of its active metabolite."( Leflunomide as a novel treatment option in severe atopic dermatitis.
Pfeiffer, C; Schmitt, J; Wozel, G, 2004
)
2.49
"Leflunomide is a disease-modifying antirheumatic drug that inhibits paw swelling and joint destruction in type II collagen-induced arthritis in mice and it also delays disease progression in patients with rheumatoid arthritis (RA), through inhibiting proliferation and cytokine production of T cells, via the blocking of de-novo pyrimidine biosynthesis by its active metabolite, A771726. "( The active metabolite of leflunomide, A771726, inhibits both the generation of and the bone-resorbing activity of osteoclasts by acting directly on cells of the osteoclast lineage.
Arai, Y; Hakeda, Y; Kaneda, T; Kobayashi, Y; Kumegawa, M; Sato, T; Shin, K; Ueyama, S; Yoshida, Y, 2004
)
2.07
"Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by formation of A77 1726. "( A rapid and simple determination of A77 1726 in human serum by high-performance liquid chromatography and its application for optimization of leflunomide therapy.
Brouwers, JR; Jansen, TL; Raemaekers, J; van Roon, EN; van Wanrooy, M; Yska, JP, 2004
)
1.97
"Leflunomide (LFL) is a modern immunomodulating medication belonging to the group of drugs that favourably affect the course of rheumatoid arthritis (RA). "( Leflunomide in the treatment of refractory rheumatoid arthritis.
Andreev, SA; Batalov, AZ; Kuzmanova, SI; Russafov, PB; Solakov, PT; Staikova, ND, 2003
)
3.2
"Leflunomide is a novel immunosuppressive and anti-inflammatory agent for the treatment of autoimmune disease. "( Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor kappaB.
Asano, T; Hayashi, H; Imao, M; Imose, M; Kimura, K; Moriwaki, H; Nagaki, M; Naiki, T; Osawa, Y; Takai, S, 2004
)
3.21
"Leflunomide is a new oral disease modifying antirheumatic drug with a good safety profile."( Lupus erythematosus with leflunomide: induction or reactivation?
Gensburger, D; Kanitakis, J; Kawashima, M; Marotte, H; Miossec, P, 2005
)
2.07
"Leflunomide is a novel immunosuppressive agent with promising activity for xenotransplantation. "( Effects of a short course of leflunomide on T-independent B-lymphocyte xenoreactivity and on susceptibility of xenografts to acute or chronic rejection.
Goebels, J; Lin, Y; Rutgeerts, O; Segers, C; Verbeken, E; Waer, M; Yan, Y; Yu, L, 2005
)
2.06
"Leflunomide is an immunomodulatory agent that was recently approved for the treatment of rheumatoid arthritis (RA). "( Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis.
Bambery, P; Govindrajan, S; Khullar, M; Reddy, SV; Wanchu, A, 2005
)
3.21
"Leflunomide is an effective disease modifying antirheumatic drug (DMARD) in RA."( Effects of the active metabolite of leflunomide, A77 1726, on cytokine release and the MAPK signalling pathway in human rheumatoid arthritis synoviocytes.
Beneytout, JL; Bertin, P; Léger, DY; Liagre, B; Trèves, R; Vergne-Salle, P, 2005
)
1.32
"Leflunomide (LEF) is a selective inhibitor of de novo pyrimidine synthesis, currently used in the treatment of rheumatoid arthritis. "( [Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial].
Bao, CD; Cai, GY; Chen, XM; Cui, TG; Hou, FF; Li, YN; Lu, FM; Mei, CL; Ni, ZH; Qian, JQ; Wang, GB; Wang, HY; Zhang, FS; Zhao, MH; Zhao, XZ; Zhu, TY; Zou, WZ, 2005
)
2.03
"Leflunomide is a long-term treatment option for patients with predominantly joint disease."( [Psoriasis arthritis--long-term treatment of two patients with leflunomide].
Schmitt, J; Wozel, G, 2004
)
1.28
"Leflunomide is a pyrimidine synthesis inhibitor used in the treatment of rheumatoid arthritis. "( Population pharmacokinetics of the active metabolite of leflunomide in pediatric subjects with polyarticular course juvenile rheumatoid arthritis.
Bhargava, VO; Kovacs, SJ; Ludden, TM; Shi, J; Wang, Y, 2005
)
2.02
"Leflunomide is a new drug for the treatment of rheumatoid arthritis. "( [Leflunomide-related severe axonal neuropathy].
Antoine, JC; Camu, W; Coudeyre, E; Gabelle, A; Hillaire-Buys, D, 2005
)
2.68
"Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals."( Treatment of renal allograft polyoma BK virus infection with leflunomide.
Atwood, W; Foster, P; Garfinkel, M; Gillen, D; Harland, R; Javaid, B; Jordan, J; Josephson, MA; Kadambi, P; Meehan, S; Millis, MJ; Sadhu, M; Thistlethwaite, RJ; Williams, J, 2006
)
1.3
"Leflunomide is an isoxazole derivative, and a unique immunomodulatory agent."( Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver.
Fadillioglu, E; Karaman, A; Tas, E; Turkmen, E; Yilmaz, Z, 2006
)
1.37
"Leflunomide is a novel drug with both immunosuppressive and anti-CMV properties."( Treatment of multidrug-resistant cytomegalovirus retinitis with systemically administered leflunomide.
Chan, LK; Levi, ME; Mandava, N; Olson, JL; Weinberg, A, 2006
)
1.28
"Leflunomide is a disease-modifying antirheumatic drug for the treatment of active rheumatoid arthritis and psoriatic arthritis. "( [Skin ulceration after leflunomide treatment in two patients with rheumatoid arthritis].
Jakob, A; Porstmann, R; Rompel, R, 2006
)
2.09
"Leflunomide is an immunomodulating and disease-modifying antirheumatic drug with anti-inflammatory and immunosuppressive activity, exhibiting an extremely long in vivo half life."( Severe atopic dermatitis and leflunomide: first clinical experience and highlights of pertinent experimental data.
Pfeiffer, C; Vitéz, L; Wozel, G, 2006
)
1.35
"Leflunomide is a new immunosuppressive drug recently introduced in the treatment of rheumatoid and psoriatic arthritis."( Anti-Jo-1 antibody positive polymyositis--successful therapy with leflunomide.
Lange, U; Müller-Ladner, U; Piegsa, M; Strunk, J, 2006
)
1.29
"Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in Japan since August 2003. "( Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis.
Hirabayashi, Y; Kobayashi, N; Kudo, K; Shimizu, H, 2006
)
3.22
"Leflunomide is an immunomodulatory agent that has been approved for treatment of active RA."( Low dose leflunomide activates PI3K/Akt signalling in erythroleukemia cells and reduces apoptosis induced by anticancer agents.
Beneytout, JL; Leger, DY; Liagre, B, 2006
)
1.47
"Leflunomide (LEF) is a prodrug that is rapidly converted to its active metabolite A77 1726, that inhibits the novo pyrimidine nucleotide biosynthesis, mediated especially by the dihydroorotate dehidrogenase (DHODH). "( Leflunomide in clinical practice.
Dougados, M; Pinto, P,
)
3.02
"Leflunomide is an immunosuppressive agent that inhibits de novo synthesis of pyrimidine nucleotides and the activity of protein tyrosine kinase. "( Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice.
Fukushima, R; Hirashiba, M; Hishikawa, A; Kanamori, S; Kaneto, M; Kato, I; Muranaka, RI; Nakamura, K,
)
1.79
"Leflunomide is a relatively new disease modifying antirheumatic drug (DMARD) and a number of studies evaluating its effectiveness and safety in daily medical practice is limited."( [Leflunomide as a second choice treatment in patients with rheumatoid arthritis].
Bachta, A; Dudek, A; Raczkiewicz-Papierska, A; Sułek, M; Tłustochowicz, M; Zawadyl, B, 2007
)
2.69
"Leflunomide is a drug used clinically in the treatment of rheumatoid arthritis."( Leflunomide inhibits PDK1/Akt pathway and induces apoptosis of human mast cells.
Nakayamada, S; Ra, C; Saito, K; Sawamukai, N; Tanaka, Y; Yamaoka, K, 2007
)
2.5
"Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-alpha-induced cellular responses. "( Leflunomide-induced subacute cutaneous lupus erythematosus with erythema multiforme-like lesions.
Alessi, E; Barbareschi, M; Del Papa, N; Marzano, AV; Ramoni, S, 2008
)
3.23
"Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). "( Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients.
Bohanec Grabar, P; Dolzan, V; Logar, D; Rozman, B; Suput, D; Tomsic, M, 2008
)
2.04
"Leflunomide is a novel immunosuppressive compound that is effective in the treatment of animal models of autoimmune disease and human rheumatoid arthritis. "( The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis.
Caulfield, JP; Cherwinski, HM; Cheung, P; Cohn, RG; Nakano, G; Ransom, JT; Webster, DJ; Xu, YZ; Young, JM, 1995
)
2.05
"Leflunomide is a novel and effective immunosuppressant that holds promise as a therapeutic agent, but the mechanism of action is unknown. "( The immunosuppressant leflunomide inhibits lymphocyte progression through cell cycle by a novel mechanism.
Cherwinski, HM; Devens, B; McCarley, D; Ransom, JT; Schatzman, R, 1995
)
2.05
"Leflunomide is a potent immunosuppressant that inhibits both T-cell and B-cell activity."( Measurement of the active leflunomide metabolite (A77 1726) by reverse-phase high-performance liquid chromatography.
Dias, VC; LeGatt, DF; Lucien, J; Yatscoff, RW, 1995
)
1.31
"Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. "( Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats.
Lang, LS; Robertson, SM, 1994
)
3.17
"Leflunomide is an isoxazole derivative that has the ability to prevent acute rejection of cardiac, renal, and skin transplants in strongly rejecting rat models. "( Leflunomide controls rejection in hamster to rat cardiac xenografts.
Chong, AS; Foster, P; Frieders, D; Koukoulis, G; McChesney, L; Sankary, H; Williams, JW; Xiao, F; Yang, J, 1994
)
3.17
"Leflunomide is an isoxazole with newly discovered immunosuppressive properties. "( An evaluation of leflunomide in the canine renal transplantation model.
Foster, PF; Haklin, M; McChesney, LP; Sankary, HN; Sharma, S; Williams, JW; Xiao, F, 1994
)
2.07
"Leflunomide is a compound recently shown to reduce T and B cell-mediated responses in a number of experimental rat, mouse, and human systems. "( Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine.
Chong, AS; Clardy, C; Foster, P; McChesney, L; Sankary, H; Williams, JW; Xiao, F, 1994
)
3.17
"Leflunomide is a novel immunomodulating drug that has recently been demonstrated to prevent acute rejection and reverse ongoing rejection of kidney and cardiac allografts in rats. "( Leflunomide, a novel immunosuppressive agent. The mechanism of inhibition of T cell proliferation.
Chong, AS; Finnegan, A; Foster, P; Gebel, H; Jiang, X; Sankary, HN; Williams, JW, 1993
)
3.17
"Leflunomide is an anti-inflammatory and immunosuppressive agent which blocks proliferation of transformed cells and mitogen stimulated normal lymphocytes but does not block T cell signaling mechanisms at antiproliferative concentrations. "( Leflunomide interferes with pyrimidine nucleotide biosynthesis.
Ballaron, SJ; Byars, N; Cherwinski, HM; Nakano, GM; Ransom, JT; Young, JM, 1995
)
3.18
"Leflunomide is an immunosuppressive drug capable of inhibiting cellular and humoral mediated responses in vivo. "( Regulation of B cell function by the immunosuppressive agent leflunomide.
Bremer, EG; Chong, AS; Finnegan, A; Siemasko, KF; Williams, JW, 1996
)
1.98
"Leflunomide is a novel immunomodulatory drug representing a new small molecule class of substances which are structurally unrelated to previously described immunomodulatory/immunosuppressive compounds. "( The immunosuppressant leflunomide blocks the yeast Saccharomyces cerevisiae cell cycle at the G1 phase.
Fujimura, H, 1996
)
2.05
"Leflunomide (Lef) is a novel immunosuppressant that can prevent islet allograft and xenograft rejection. "( In vivo effects of leflunomide on normal pancreatic islet and syngeneic islet graft function.
Chong, AS; Foster, P; Gebel, H; Guo, Z; Jensik, SC; McChesney, L; Mital, D; Sankary, HN; Shen, J; Williams, JW, 1997
)
2.07
"Leflunomide is a new immunomodulatory drug that is effective in experimental models of autoimmune diseases and in allo or xenotransplantation. "( Leflunomide and malononitrilamides.
Morris, RE; Silva Júnior, HT, 1997
)
3.18
"Leflunomide is an immunosuppressive drug capable of inhibiting T and B cell responses in vivo. "( Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgG1 production.
Chong, AS; Finnegan, A; Gong, H; Jäck, HM; Siemasko, K; Williams, JW, 1998
)
1.97
"Leflunomide is a new low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate-dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. "( The effects of leflunomide and cyclosporin A on rejection of cardiac allografts in the rat.
Ekberg, H; Hedlund, G; Ostraat, O; Qi, ZQ; Tufveson, G, 1998
)
2.1
"Leflunomide is a new anti-inflammatory and immunomodulating agent which is showing promise in several immune disorders, especially rheumatoid arthritis. "( Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma.
Eber, E; McMenamin, C; Sly, PD; Uhlig, T, 1998
)
3.19
"Leflunomide is a novel isoxazol drug with disease modifying properties for the treatment of rheumatoid arthritis (RA). "( Clinical experience with leflunomide in rheumatoid arthritis. Leflunomide Investigators' Group.
Rozman, B, 1998
)
2.05
"Leflunomide is an immunosuppressive prodrug which prevents allograft rejection in several animal model systems and may, therefore, have clinical application in organ transplant recipients. "( Dose-dependent enhancing and inhibitory effects of A77 1726 (leflunomide) on cytotoxic T lymphocyte induction.
Hoskin, DW; James, H; Lee, TD; Makrigiannis, AP; Taylor, RM, 1998
)
1.98
"Leflunomide is a novel immunosuppressive and antiinflammatory agent currently being tested for treatment of autoimmune diseases and transplant rejection. "( Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression.
Aggarwal, BB; Manna, SK, 1999
)
2.08
"Leflunomide is an experimental drug with demonstrated ability to prevent and reverse acute allograft and xenograft rejection. "( In vivo activity of leflunomide: pharmacokinetic analyses and mechanism of immunosuppression.
Blinder, L; Chong, AS; Clardy, C; Foster, P; Huang, W; Liu, W; Luo, J; Ma, L; Shen, J; Williams, JA; Xiao, F; Xu, W; Xu, X, 1999
)
2.07
"Leflunomide is a new DMARD that may have a high potential for success in combination therapy with methotrexate."( Methotrexate and leflunomide: biochemical basis for combination therapy in the treatment of rheumatoid arthritis.
Kremer, JM, 1999
)
1.36
"Leflunomide is an immunomodulatory drug which acts by inhibiting dihydroorotic acid dehydrogenase, the fourth enzyme of pyrimidine biosynthesis. "( Simultaneous separation by high-performance liquid chromatography of carbamoyl aspartate, carbamoyl phosphate and dihydroorotic acid.
Carrey, EA; Fairbanks, LD; Kirschbaum, B; Rückemann, K; Simmonds, HA; Swaminathan, R, 1999
)
1.75
"Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA)."( Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group.
Caldwell, J; Cannon, G; Cohen, S; Fleischmann, R; Fox, R; Furst, D; Hurley, F; Kaine, J; Loew-Friedrich, I; Moreland, L; Olsen, N; Schiff, M; Sharp, J; Strand, V; Weaver, A, 1999
)
2
"Leflunomide is an immunomodulatory drug that may exert its effects by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP)."( Mechanism of action for leflunomide in rheumatoid arthritis.
Fox, RI; Frangou, CG; Herrmann, ML; Kirschbaum, BJ; Morris, RE; Strand, V; Wahl, GM, 1999
)
1.33
"Leflunomide is a disease-modifying antirheumatic drug which reduces the signs and symptoms of inflammatory arthritis and delays the radiological progression of disease in adult patients with active rheumatoid arthritis. "( Leflunomide: a review of its use in active rheumatoid arthritis.
Jarvis, B; Prakash, A, 1999
)
3.19
"Leflunomide is a newer DMARD that reduces pyrimidine synthesis, thus decreasing rheumatoid inflammation."( New drugs for the treatment of rheumatoid arthritis.
Megeff, C; Schuna, AA, 2000
)
1.03
"Leflunomide is a novel immunomodulating drug that has recently been approved as a disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). "( Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients.
Breedveld, FC; de Koster, BM; Elferink, JG; Kraan, MC; Post, WJ; Tak, PP, 2000
)
1.98
"Leflunomide is a novel drug recently introduced for treatment of rheumatoid arthritis as a DMARD (disease-modifying antirheumatic drug). "( Severe pancytopenia after leflunomide in rheumatoid arthritis.
Allinger, S; Auer, J; Hinterreiter, M; Kirchgatterer, A; Knoflach, P, 2000
)
2.05
"Leflunomide is a DMARD with a novel mechanism of action that has been approved as a first-line treatment for RA."( New and future drug therapies for rheumatoid arthritis.
Simon, LS; Yocum, D, 2000
)
1.03
"Leflunomide is a safe and efficacious addition to the roster of anti-rheumatic drugs."( Efficacy and safety of leflunomide in active rheumatoid arthritis.
Emery, P; Smolen, JS, 2000
)
1.34
"Leflunomide (LFM) is a novel anti-inflammatory and immunosuppressive drug, and inhibits the growth of cytokine-stimulated lymphoid cells in vitro. "( The immunosuppressive drug leflunomide affects mating-pheromone response and sporulation by different mechanisms in Saccharomyces cerevisiae.
Fujimura, H, 2000
)
2.05
"Leflunomide is a reversible inhibitor of "de novo" synthesis of pyrimidine, resulting in a restriction of lymphocyte proliferation."( [Leflunomide for active rheumatoid arthritis].
Andresen, PN; Hansen, G; Hørslev-Petersen, K, 2000
)
1.94
"Leflunomide is a selective inhibitor of de novo pyrimidine synthesis. "( Leflunomide: mode of action in the treatment of rheumatoid arthritis.
Breedveld, FC; Dayer, JM, 2000
)
3.19
"Leflunomide is a pyrimidine biosynthesis inhibitor that has recently been approved for treatment of rheumatoid arthritis. "( Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal protein kinase, and apoptosis.
Aggarwal, BB; Manna, SK; Mukhopadhyay, A, 2000
)
3.19
"Leflunomide is a new and effective disease-modifying antirheumatic drug. "( Leflunomide: new antirheumatic drug. Effect on pregnancy outcomes.
Koren, G; Kozer, E; Moretti, ME, 2001
)
3.2
"Leflunomide is a new immunosuppressive drug whose active metabolite, A77 1726, impairs cellular nucleotide metabolism by inhibiting the dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme of de novo pyrimidine synthesis. "( Suppression of experimental autoimmune neuritis by leflunomide.
Hartung, HP; Jung, S; Korn, T; Toyka, K, 2001
)
2.01
"Leflunomide is an isoxazol derivative with immunosuppressive capacities in various experimental allo- and xenotransplantation models. "( Leflunomide-mediated suppression of antiviral antibody and Tcell responses: differential restoration by uridine.
Fehr, T; Ochsenbein, AF; Pinschewer, DD; Zinkernagel, RM, 2001
)
3.2
"Leflunomide is a novel disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis. "( [Leflunomide--a new disease modifying anti-rheumatic agent].
Johnsen, V; Kvien, TK; Rødevand, E, 2001
)
2.66
"Leflunomide is a safe and efficacious addition to the roster of antirheumatic drugs, but further clinical trials and experience from clinical practice are needed in the evaluation of its place as a disease-modifying agent."( [Leflunomide--a new disease modifying anti-rheumatic agent].
Johnsen, V; Kvien, TK; Rødevand, E, 2001
)
2.66
"Leflunomide is a new second-line drug for rheumatoid arthritis. "( [Leflunomide in the treatment of rheumatoid arthritis].
Wendling, D, 2002
)
2.67
"Leflunomide is an antirheumatic drug. "( [Leflunomide in systemic lupus erythematosus].
Kessel, A; Toubi, E, 2002
)
2.67
"Leflunomide is a new antirheumatic drug. "( Therapeutic effects of leflunomide, a new antirheumatic drug, on glomerulonephritis induced by the antibasement membrane antibody in rats.
Gotoh, K; Hayashi, S; Inazu, M; Inoue, T; Ogawa, T, 1991
)
2.03

Effects

Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1. It has a rapid onset of action (within 4 weeks) which is significantly faster than placebo and sulfasalazine.

Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD) It has both antiviral and immunosuppressive effects, which may mitigate host response to bacterial translocation.

ExcerptReferenceRelevance
"Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NF-ATc1, the master switch regulator for osteoclast differentiation. "( The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells c1.
Isobe, M; Kim, S; Kodama, T; Koga, T; Kurosawa, H; Löeffler, M; Morishita, Y; Nakagawa, T; Takayanagi, H; Taniguchi, T; Urushibara, M, 2004
)
2.08
"Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1, the master switch regulator for osteoclast differentiation."( [Disease modifying antirheumatic drugs with inhibitory effect on osteoclastogenesis].
Urushibara, M, 2005
)
1.05
"Leflunomide has a rapid onset of action (within 4 weeks) which is significantly faster than placebo and sulfasalazine."( Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis.
Alldred, A; Emery, P, 2001
)
2.47
"Leflunomide has shown promising results in BKVAN."( Leflunomide in the treatment of BK polyomavirus associated nephropathy in kidney transplanted patients - A systematic review.
Dräger, DL; Hakenberg, OW; Kranz, J; Neumann, T; Schneidewind, L, 2020
)
2.72
"Leflunomide has both antiviral and immunosuppressive effects, and clinical research has demonstrated its clinical efficacy against BKVN."( Use of Leflunomide as an Antiviral Agent with Everolimus for BK Virus Nephropathy Patients After Kidney Transplantation: A Case Series.
Shirai, H; Tojimbara, T; Yamazaki, T, 2020
)
1.73
"Leflunomide has protective effects on podocytes in high glucose. "( [Effects of leflunomide on podocytes exposed to high glucose condition and its mechanism].
Li, RS; Ren, XJ; Yu, WM; Zhao, X, 2013
)
2.21
"Leflunomide has important immunomodulatory and anti-inflammatory effects, which may mitigate host response to bacterial translocation."( Protective effect of leflunomide against oxidative intestinal injury in a rodent model of sepsis.
Fadillioglu, E; Karaman, A; Ozturk, E; Samdancı, E; Surucu, M, 2014
)
1.44
"Leflunomide has been successfully used for treating rheumatoid arthritis and psoriatic arthritis for many years."( Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases.
Brooks, JB; Fragoso, YD, 2015
)
2.58
"Leflunomide has been shown to be effective in the treatment of systemic CMV viremia."( Utility of Leflunomide in the Treatment of Drug Resistant Cytomegalovirus Retinitis.
Goldstein, DA; Jumroendararasame, C; Minkus, CL; Pursell, K; Rifkin, LM, 2017
)
1.57
"Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking."( Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.
Ariza-Heredia, E; Chemaly, RF; Doan, V; El Chaer, F; Jan, A; Mori, N; Oliver, N; Shah, D; Tayar, J; Tverdek, F; Wang, E, 2016
)
1.43
"Leflunomide has inhibitory effects on dihydroorotate-dehydrogenase activity and protein tyrosine kinase activity. "( Critical periods for the teratogenicity of immune-suppressant Leflunomide in mice.
Fukushima, R; Hirashiba, M; Hishikawa, A; Kanamori, S; Kaneto, M; Kitagawa, H; Muranaka, R, 2009
)
2.04
"Leflunomide has been used off-label in renal transplantation because of the attractive combination of antiviral and immunosuppressive effects. "( Leflunomide use in renal transplantation.
Leca, N, 2009
)
3.24
"Leflunomide has immunosuppressive and antiviral properties and may be an alternative treatment agent."( Leflunomide therapy for polyomavirus-induced allograft nephropathy: efficient BK virus elimination without increased risk of rejection.
Benzing, T; Gerke, P; Geyer, M; Krumme, B; Teschner, S; Walz, G; Wilpert, J,
)
2.3
"Leflunomide has high hepatotoxic potential, especially when combined with methotrexate."( [Hepatotoxicity induced by new immunosuppressants].
Andrade, RJ; Cotta, J; Lucena, MA; Robles, M; Toscano, E, 2010
)
1.08
"Leflunomide has been reported as an alternative therapy in sarcoidosis. "( Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis.
Bandyopadhyay, D; Chapman, JT; Culver, DA; Lazar, CA; Parambil, JG; Pearson, K; Sahoo, DH; Xu, M, 2011
)
2.11
"Leflunomide has demonstrated usefulness in treating cutaneous psoriasis along with other dermatologic and rheumatologic conditions."( Leflunomide in dermatology.
Boyd, AS, 2012
)
2.54
"Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo."( Leflunomide for cytomegalovirus: bench to bedside.
Chacko, B; John, GT, 2012
)
2.54
"Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring."( Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection.
Baliga, P; Bratton, C; Chavin, K; Krisl, JC; McGillicuddy, J; Pilch, N; Taber, DJ; Thomas, B, 2012
)
2.54
"Leflunomide has been shown to possess antiviral activity against several viruses."( Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis with leflunomide in an HIV-infected man.
Henao-Martínez, AF; Levi, ME; Waldman, WJ; Weinberg, A, 2012
)
1.32
"Leflunomide, a drug which has been approved in Germany for the therapy of rheumatoid arthritis, inhibits the activity of several growth factors in vitro."( [Leflunomide reduces the angiogenesis score and tumor growth of subcutaneously implanted colon carcinoma cells in the mouse model].
Mall, JW; Myers, JA; Philipp, AW; Pollmann, C; Saclarides, TJ; Xu, X, 2002
)
1.95
"Leflunomide has no known influence on adenosine metabolism, so different pathogenetic mechanisms must be assumed for the induction of nodulosis by leflunomide."( [Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy].
Becker-Capeller, D; Braun, MG; Van Rhee, R, 2004
)
1.27
"Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NF-ATc1, the master switch regulator for osteoclast differentiation. "( The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells c1.
Isobe, M; Kim, S; Kodama, T; Koga, T; Kurosawa, H; Löeffler, M; Morishita, Y; Nakagawa, T; Takayanagi, H; Taniguchi, T; Urushibara, M, 2004
)
2.08
"Leflunomide has excellent antiviral activity against cytomegalovirus (CMV) in animal models and is considerably less expensive than intravenous ganciclovir. "( Leflunomide therapy for cytomegalovirus disease in renal allograft recepients.
Chandy, S; Jacob, CK; John, GT; Manivannan, J; Peter, S, 2004
)
3.21
"Leflunomide has been evaluated in RA patients as monotherapy and in combination with methotrexate."( Leflunomide.
Cannon, GW; Kremer, JM, 2004
)
2.49
"Leflunomide has been subsequently used with success in several animal models of tissue and organ allograft and of autoimmune disease including collagen- and adjuvant-induced arthritis, interstitial nephritis, myasthenia gravis, and systemic lupus erythematosus."( Benefit/risk of leflunomide in rheumatoid arthritis.
Cannon, GW; Kremer, JM,
)
1.2
"Leflunomide has been shown to cause cell specific inhibition of inducible nitric oxide synthase (iNOS) activation in animal models."( Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis.
Bambery, P; Govindrajan, S; Khullar, M; Reddy, SV; Wanchu, A, 2005
)
2.49
"Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1, the master switch regulator for osteoclast differentiation."( [Disease modifying antirheumatic drugs with inhibitory effect on osteoclastogenesis].
Urushibara, M, 2005
)
1.05
"As leflunomide has little effect on psoriatic skin lesions, additional topical therapy is necessary."( [Psoriasis arthritis--long-term treatment of two patients with leflunomide].
Schmitt, J; Wozel, G, 2004
)
1.08
"Leflunomide has shown promise in the treatment of psoriasis."( Leflunomide improves psoriasis in patients with psoriatic arthritis: an in-depth analysis of data from the TOPAS study.
Behrens, F; Falk, F; Kaltwasser, JP; Nash, P; Thaçi, D, 2006
)
3.22
"Leflunomide has been reported to show antitumor potential through inhibition of cancer cell proliferation."( Low dose leflunomide activates PI3K/Akt signalling in erythroleukemia cells and reduces apoptosis induced by anticancer agents.
Beneytout, JL; Leger, DY; Liagre, B, 2006
)
1.47
"Leflunomide has been reported as an immunomodulating agent which acts on a variety of cells including T- and B-lymphocytes. "( Protective effect of leflunomide on the natural course of Leishmania major-induced disease in genetically susceptible BALB/c mice.
Asmuss, PA; Humborg, C; Röllinghoff, M; Solbach, W; Zimmermann, S, 1995
)
2.05
"Leflunomide has been identified as an immunoregulatory and anti-inflammatory compound. "( Inhibition of murine IgE and immediate cutaneous hypersensitivity responses to ovalbumin by the immunomodulatory agent leflunomide.
Bartlett, RR; Jarman, ER; Kuba, A; Montermann, E; Reske-Kunz, AB, 1999
)
1.95
"Leflunomide (Arava) has recently been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis (RA). "( Mechanism of action for leflunomide in rheumatoid arthritis.
Fox, RI; Frangou, CG; Herrmann, ML; Kirschbaum, BJ; Morris, RE; Strand, V; Wahl, GM, 1999
)
2.05
"Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD)."( Treatment options for rheumatoid arthritis: celecoxib, leflunomide, etanercept, and infliximab.
Chong, BS; Lowder, DM; Luong, BT, 2000
)
1.28
"Leflunomide (Arava) has recently been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis (RA). "( Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases.
Herrmann, ML; Kirschbaum, BJ; Schleyerbach, R, 2000
)
3.19
"Leflunomide has exerted inhibitory activity in animal models of RA."( Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis.
Goldenberg, MM, 1999
)
2.47
"Leflunomide has shown an efficacy and a pattern of mild and serious side effects similar to methotrexate and sulphasalazine."( [Leflunomide for active rheumatoid arthritis].
Andresen, PN; Hansen, G; Hørslev-Petersen, K, 2000
)
1.94
"Leflunomide has recently been used effectively for the treatment of RA and may be useful for the management of patients with FS."( Treatment of Felty's syndrome with leflunomide.
Khan, W; Talip, F; Walker, N; Zimmermann, B, 2001
)
1.31
"Leflunomide has a rapid onset of action (within 4 weeks) which is significantly faster than placebo and sulfasalazine."( Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis.
Alldred, A; Emery, P, 2001
)
2.47
"Leflunomide has been shown to be as effective as sulfasalazine and methotrexate (MTX) in placebo-controlled trials."( New disease modifying agents in adult rheumatoid arthritis.
Koh, ET, 2001
)
1.03
"Leflunomide has recently been introduced for systemic treatment of rheumatoid arthritis. "( Vasculitis occurring during leflunomide therapy.
Balslev, E; Holm, EA; Jemec, GB, 2001
)
2.05
"Leflunomide has been shown to be very effective in preventing and curing several autoimmune animal diseases. "( Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection.
Bartlett, RR; Bremer, E; Dimitrijevic, M; Germann, T; Küchle, CC; Mattar, T; Rüde, E; Schorlemmer, HU; Thoenes, GH; Zielinski, T, 1991
)
3.17

Actions

Leflunomide appeared to cause regression of experimental endometriosis in rats. Can also inhibit expression of TGF-beta1, MCP-1 at the level of gene and protein.

ExcerptReferenceRelevance
"Leflunomide can inhibit high glucose-induced podocyte apoptosis. "( [Inhibition of leflunomide active metabolite A771726 on high glucose-induced podocyte apoptosis].
Li, RS; Qiao, X; Yu, WM; Yuan, YC, 2011
)
2.16
"Leflunomide can inhibit hepatocyte damage by inhibiting proinflammatory cytokine release from KCs."( Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells.
Chen, JQ; Li, J; Xu, SY; Yao, HW, 2004
)
3.21
"Leflunomide appeared to cause regression of experimental endometriosis in rats."( Leflunomide--an immunomodulator--induces regression of endometrial explants in a rat model of endometriosis.
Aytan, H; Batioglu, S; Uygur, D; Zergeroglu, S, 2006
)
3.22
"Leflunomide could also inhibit the expression of TGF-beta1, MCP-1 at the level of gene and protein in renal tissue (P<0.05 or P<0.01)."( [Study on protective effects and its mechanism of leflunomide on renal tissue in rat IgA nephropathy model].
Liu, X; Lou, TQ; Peng, H; Tang, H; Tang, Y; Wang, C, 2008
)
1.32
"Leflunomide was able to inhibit p59fyn and p56lck activity in in vitro tyrosine kinase assays."( Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide.
Bremer, EG; Chong, AS; Finnegan, A; Williams, JW; Xu, X, 1995
)
1.23

Treatment

Treatment with leflunomide (LEF), cyclosporine (CsA), mycophenolate mofetil (MMF), 15-deoxyspergualin, and rapamycin alone or in combination had an insufficient inhibitory effect on ICC xenograft rejection. In vitro, treatment with leFlnomide prevented allergen-induced mast cell degranulation in vitro because the mast cells lacked IgE on their surface.

ExcerptReferenceRelevance
"Leflunomide treatment failure was defined as failure to achieve remission, the need to add other DMARDs for controlling attacks and disease progression to chronic arthritis during treatment with leflunomide."( Efficacy of leflunomide in the treatment of palindromic rheumatism.
Esalatmanesh, K; Khabbazi, A; Sadri, M, 2022
)
1.82
"Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy."( Use of leflunomide in patients with chronic hypersensitivity pneumonitis.
Culver, DA; Li, M; Noh, S; Pande, A; Sahoo, D; Wang, X; Yadav, R, 2020
)
1.73
"Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. "( Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells.
Chen, S; Couch, L; Guo, L; Ning, B; Qing, T; Ren, Z; Shi, L; Xuan, J; Yu, D, 2017
)
2.13
"The leflunomide treatment response rate was 93.3%."( Efficacy of leflunomide for treatment of refractory inflammatory colorectal polyps in 15 Miniature Dachshunds.
Eguchi, N; Fukushima, K; Igarashi, H; Kanemoto, H; Nakashima, K; Ohmi, A; Ohno, K; Takahashi, M; Tsujimoto, H, 2016
)
1.29
"Leflunomide pretreatment significantly ameliorated pancreatic hemorrhage, edema, and neutrophil infiltration and decreased histopathological score compared with the untreated severe necrotizing pancreatitis group (pathological score [mean +/- SEM]: 6.70 +/- 1.19 vs 12.36 +/- 1.08 in the leflunomide treated and untreated groups, respectively, P < 0.01). "( Leflunomide: is a new oral agent in treatment of acute pancreatitis?
Kaptanoglu, B; Kutluana, U; Nart, D; Oruc, N; Ozutemiz, O; Yonetci, N, 2010
)
3.25
"Leflunomide treatment, as employed in actual clinical practice, was well tolerated and resulted in substantial improvements in joint and functional status outcomes in children with JIA. "( Effectiveness of leflunomide in patients with juvenile idiopathic arthritis in clinical practice.
Foeldvari, I; Wierk, A, 2010
)
2.14
"Leflunomide treatment was according to label instructions."( Leflunomide in the treatment of patients with early rheumatoid arthritis--results of a prospective non-interventional study.
Bornholdt, K; Hein, G; Kellner, H, 2010
)
2.52
"Leflunomide treatment suppressed cytokine release from circulating immune cells. "( Clinical efficacy of leflunomide in primary Sjogren's syndrome is associated with regulation of T-cell activity and upregulation of IL-7 receptor α expression.
Bijlsma, JW; Bikker, A; Kruize, AA; Lafeber, FP; van der Wurff-Jacobs, KM; van Roon, JA; van Woerkom, JM, 2012
)
2.14
"Leflunomide treatment increased regulatory T cells (Tregs; forkhead box P3+) and IL-10-positive cells but reduced IL-17- and IL-23-expressing cells in both the peripheral blood and kidney cells, indicative of down-regulation of inflammatory responses."( Aryl hydrocarbon receptor agonist, leflunomide, protects the ischemic-reperfused kidney: role of Tregs and stem cells.
Baban, B; Liu, JY; Mozaffari, MS, 2012
)
1.38
"Leflunomide treatment was initiated at 20 mg/day and increased to 30 mg/day after 12 weeks and, in patients with partial remission, to 40 mg/day after 24 weeks."( Maintenance of remission with leflunomide in Wegener's granulomatosis.
Fink, C; Gross, WL; Lamprecht, P; Metzler, C; Reinhold-Keller, E, 2004
)
1.33
"Leflunomide treatment also influences xenoantigen expression, as nontolerant B lymphocytes provoke IgM XAb formation and rejection of only second xenografts (transplanted without leflunomide) and not of first xenografts (transplanted with leflunomide treatment)."( Effects of a short course of leflunomide on T-independent B-lymphocyte xenoreactivity and on susceptibility of xenografts to acute or chronic rejection.
Goebels, J; Lin, Y; Rutgeerts, O; Segers, C; Verbeken, E; Waer, M; Yan, Y; Yu, L, 2005
)
1.34
"Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical."( A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.
Balakrishnan, N; Chandy, S; Chandy, SJ; Fleming, DH; Jacob, CK; John, GT; Kirubakaran, MG; Krishnamurthy, K; Manivannan, J; Peter, S, 2005
)
2.07
"Leflunomide pretreatment significantly inhibited the deposition of type I collagen in HSCs and the proliferation of primary HSC by interrupting the three proliferative signal transduction pathways in vitro, which was indicated by [(3)H]thymidine incorporation and cell cycle analysis."( Suppressive effects of leflunomide on leptin-induced collagen I production involved in hepatic stellate cell proliferation.
Jin, Y; Li, J; Lü, XW; Si, HF, 2007
)
1.37
"Leflunomide treatment also improved quality of life and showed a favourable safety profile."( Leflunomide in psoriatic arthritis.
Kaltwasser, JP, 2007
)
2.5
"In leflunomide-treated patients a significant reduction of MMP activity levels was observed as early as at the 4 months timepoint persisting thereafter, whereas in methotrexate-treated patients the reduction was seen at 1 year."( Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with alpha2 macroglobulin in serum of rheumatoid arthritis patients.
DeGroot, J; Hanemaaijer, R; Huizinga, TW; Kraan, MC; Tchetverikov, I; van El, B, 2008
)
2.3
"Leflunomide treatment was well tolerated by 62 patients, whereas 43 patients discontinued the treatment within the first year due to toxicity. "( Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients.
Bohanec Grabar, P; Dolzan, V; Logar, D; Rozman, B; Suput, D; Tomsic, M, 2008
)
2.04
"Leflunomide-treated allograft (15 mg/kg/day orally) and xenograft (20 mg/kg/day orally) recipients displayed significant graft prolongation to 28.2 +/- 0.7 days and 15.8 +/- 3.3 days, respectively."( Leflunomide prolongs pulmonary allograft and xenograft survival.
Gandy, KL; Gutierrez, J; Hoyt, G; Morris, RE; Reitz, BA; Robbins, RC; Yuh, DD,
)
2.3
"When leflunomide-treated cells were subjected to heat shock treatment, the cells became resistant to heat shock treatment, implying that leflunomide-mediated block to cell division results in entry from the proliferative cycle into the alternative developmental G0 phase."( The immunosuppressant leflunomide blocks the yeast Saccharomyces cerevisiae cell cycle at the G1 phase.
Fujimura, H, 1996
)
1.06
"Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk)."( Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group.
Caldwell, J; Cannon, G; Cohen, S; Fleischmann, R; Fox, R; Furst, D; Hurley, F; Kaine, J; Loew-Friedrich, I; Moreland, L; Olsen, N; Schiff, M; Sharp, J; Strand, V; Weaver, A, 1999
)
2
"Leflunomide treatment appears to offer an alternative to methotrexate and sulfasalazine and is a welcome addition to the therapeutic armamentarium for treating active RA. "( Leflunomide for the treatment of rheumatoid arthritis.
Kremer, JM; Olsen, NJ; Strand, V, 1999
)
3.19
"Leflunomide treatment is beneficial in RA patients. "( Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients.
Breedveld, FC; de Koster, BM; Elferink, JG; Kraan, MC; Post, WJ; Tak, PP, 2000
)
1.98
"Leflunomide treatment was comparable to sulphasalazine and methotrexate with respect to efficacy, radiological progression and quality of life measures."( Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications.
Debroe, S; Hewitson, PJ; McBride, A; Milne, R, 2000
)
2.47
"Leflunomide-treated rats did not mount autoantibodies as specified by ELISA (enzyme-linked immunosorbent assay) with a mixture of peripheral myelin proteins, including P2 and myelin basic protein."( Suppression of experimental autoimmune neuritis by leflunomide.
Hartung, HP; Jung, S; Korn, T; Toyka, K, 2001
)
1.28
"Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05)."( Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging.
Breedveld, FC; Emery, P; Gibbon, WW; Kraan, MC; O'Connor, PJ; Radjenovic, A; Reece, RJ; Ridgway, JP; Tak, PP; Veale, DJ, 2002
)
1.34
"Treatment with leflunomide or low doses of glucocorticoids were not associated with severe course in our cohort."( COVID-19 among patients with giant cell arteritis: a single-centre observational study from Slovenia.
Hočevar, A; Ješe, R; Kramarič, J; Rotar, Ž; Tomšič, M, 2022
)
1.06
"Treatment with leflunomide was continued until BK virus was undetectable by polymerase chain reaction in at least 2 blood samples 2 weeks apart."( Effect of Leflunomide on Treatment of Pediatric Renal Transplant Recipients With BK Virus Infection.
Askiti, V; Darema, M; Gole, E; Malakasioti, G; Mitsioni, A, 2023
)
1.65
"Treatment with leflunomide resulted in rapid BK virus clearance and preservation of renal function with no adverse effects."( Effect of Leflunomide on Treatment of Pediatric Renal Transplant Recipients With BK Virus Infection.
Askiti, V; Darema, M; Gole, E; Malakasioti, G; Mitsioni, A, 2023
)
1.67
"Treatment with leflunomide, a potent activator of mitochondrial fusion proteins, overcame inhibitory effects of fission on migration, signaling, and metastasis."( Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer.
Bevoor, A; Boppisetti, J; Buschhaus, JM; Chen, YC; Chiang, B; Cutter, AC; Eckley, S; Ghosh, P; Haley, HR; Humphries, BA; Lahann, J; Luker, GD; Luker, KE; Neale, DB; Palagama, DSW; Qyli, T; Robison, TH; Ross, BD; Sahoo, D; Sahoo, S; Spinosa, PC; Yoon, E, 2020
)
0.9
"Treatment with leflunomide tended to improve the estimated FVC slope from 0.18 ± 1.90% (SEM) of predicted per year to 4.62 ± 1.65% of predicted (NS, p = 0.118). "( Use of leflunomide in patients with chronic hypersensitivity pneumonitis.
Culver, DA; Li, M; Noh, S; Pande, A; Sahoo, D; Wang, X; Yadav, R, 2020
)
1.37
"Treatment with leflunomide was not associated with a difference from the interferon-alone group in the duration of viral shedding (hazard ratio for negative reverse-transcription PCR, 0.70 [95% confidence interval, .391-1.256]; P = .186)."( Treatment of Coronavirus Disease 2019 Patients With Prolonged Postsymptomatic Viral Shedding With Leflunomide: A Single-center Randomized Controlled Clinical Trial.
Hu, K; Hu, W; Li, X; Liu, Z; Lu, L; Wan, Z; Wang, M; Wang, T; Zeng, S; Zhang, Y; Zhao, D; Zhao, Y; Zheng, Z, 2021
)
1.18
"Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased."( Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis.
Alfieri, DF; Costa, NT; de Medeiros, FA; de Sá, MC; Dichi, I; Iriyoda, TMV; Lozovoy, MAB; Maes, M; Micheletti, PL; Reiche, EMV; Scavuzzi, BM; Sekiguchi, BA; Simão, ANC, 2018
)
1.06
"Treatment with leflunomide was started after a mean of 1.4 ± 4.1months  after BKPyVAN diagnosis."( Clinical utility of leflunomide for BK polyomavirus associated nephropathy in kidney transplant recipients: A multicenter retrospective study.
Bouvier, N; Caillard, S; Conrad, A; Duquennoy, S; Fafi-Kremer, S; Hurault De Ligny, B; Keller, N; Morelon, E; Moulin, B, 2019
)
1.18
"Treatment with leflunomide significantly prevented and treated EAU-induced ocular inflammation and decreased clinical and pathological scores compared to vehicle-treated eyes."( Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
Fang, CB; He, Y; Huang, C; Li, J; Lin, Z; Zhan, SX; Zhou, DX, 2013
)
0.98
"When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and SK-N-F1 showed dramatic inhibition of DHODH at mRNA and protein levels."( Leflunomide reduces proliferation and induces apoptosis in neuroblastoma cells in vitro and in vivo.
Cui, H; Ding, HF; Xiang, Z; Yan, X; Zhu, S, 2013
)
2.16
"Treatment with leflunomide, perindopril or curcumin alone abrogated the DEN-induced increased MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF-1α hepatic expression."( Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice.
Hamed, O; Kazem, A; Nasr, M; Selima, E, 2014
)
0.98
"Treatment with leflunomide is a reasonable option in ganciclovir-resistant infection in kidney transplant recipients, providing effective viral elimination and reconstitution of adaptive anti-CMV immunity without excess risk of graft rejection."( Leflunomide as a rescue treatment in ganciclovir-resistant cytomegalovirus infection in a seronegative renal transplant recipient--a case report.
Chmura, A; Ciszek, M; Foroncewicz, B; Mucha, K; Pączek, L, 2014
)
2.2
"Treatment with leflunomide evoked antitumor properties as indicated by reduction in tumor mass, histopathological score, number of intratumoral PCNA immunopositive nuclei. "( Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in mice: Effect on EGF and EGFR expression and tumor proliferation.
Ali, EA; Bahr, HI; Mohammad, HM; Mohammed, EA; Toraih, EA; Zaitone, SA, 2015
)
1.07
"Treatment with leflunomide, which reduces mitochondrial reactive oxygen species production and tyrosine phosphorylation, inhibits jmjd3 expression and M2 polarization, as well as development of a fibrotic phenotype."( Cu,Zn-Superoxide Dismutase-Mediated Redox Regulation of Jumonji Domain Containing 3 Modulates Macrophage Polarization and Pulmonary Fibrosis.
Carter, AB; Gu, L; He, C; Larson-Casey, JL; Murthy, S; Ryan, AJ, 2016
)
0.77
"Treatment with leflunomide (OR: 0.47; CI 95%: 0.35-0.64, p < 0.001) or rituximab (OR: 0.37; CI 95%: 0.17-0.83, p = 0.016) was associated with a lesser probability of reaching remission."( Effectiveness of treatment with biologic- and disease-modifying antirheumatic drugs in rheumatoid arthritis patients in Colombia.
Machado-Alba, JE; Machado-Duque, ME; Ruiz, AF, 2016
)
0.77
"Treatment with leflunomide was well tolerated with mostly low-grade adverse events. "( The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants.
Adelsberger, JW; Ciccone, EJ; DeGrezia, M; DerSimonian, R; Higgins, J; Read, SW; Rehm, C; Sereti, I; Starling, JM, 2010
)
1.07
"Treatment with leflunomide can improve these parameters except systolic blood pressure, BG and HbAlc."( Experimental study of leflunomide on renal protective effect and on inflammatory response of streptozotocin induced diabetic rats.
Liu, JP; Ren, XJ; Wang, H; Wang, JY; Yu, WM, 2012
)
1.03
"Treatment with leflunomide, FK778, or MPA may bear the risk to enhance HBV replication in infected patients."( The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis B virus replication in vitro.
Hoppe-Seyler, F; Hoppe-Seyler, K; Lohrey, C; Sauer, P, 2012
)
0.98
"Treatment with leflunomide reduced serum viral titres and stabilized renal function."( Native kidney BK virus nephropathy associated with chronic lymphocytic leukaemia.
Gray, M; Leonard, N; McCrory, R; Smyth, J; Woodman, A, 2012
)
0.72
"Treatment with leflunomide markedly reduced serum transaminase activities and the numbers of dead liver cells."( Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor kappaB.
Asano, T; Hayashi, H; Imao, M; Imose, M; Kimura, K; Moriwaki, H; Nagaki, M; Naiki, T; Osawa, Y; Takai, S, 2004
)
2.11
"Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats."( Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment.
Fadillioglu, E; Iraz, M; Karadag, N; Karaman, A; Kirimlioglu, H; Tas, E, 2006
)
0.92
"The treatment with leflunomide was suspended; the conditions of the patient gradually improved and he became completely asymptomatic 1 week later."( Diffuse alveolar hemorrhage after leflunomide therapy in a patient with rheumatoid arthritis.
Carloni, A; Giannakakis, K; Nori, G; Piciucchi, S; Poletti, V; Zobel, BB, 2008
)
0.94
"Treatment with leflunomide seemed to be associated with a new toxicity, hemolysis, seen in four of the 27 patients so treated."( Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients.
Davis, CL; de Boer, IH; Jefferson, JA; Kendrick, EA; Kowalewska, J; Leca, N; Muczynski, KA; Pichler, R, 2008
)
1.03
"A treatment with leflunomide, 20 mg/kg i.p., twice daily over a period of 3 days, caused no change of the lethality compared with control mice."( Effects of leflunomide on the course of listeriosis in mice. Short communication.
Hirschelmann, R; Sandow, D; Schleyerbach, R; Staffeldt, D; Wilhelms, D, 1995
)
1.01
"When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of arthritis were effectively inhibited."( Immunomodulation of rat antigen-induced arthritis by leflunomide alone and in combination with cyclosporin A.
Brauer, R; Henzgen, S; Katenkamp, D; Petrow, PK; Thoss, K, 1996
)
0.86
"Treatment with leflunomide (LEF), cyclosporine (CsA), mycophenolate mofetil (MMF), 15-deoxyspergualin, and rapamycin alone or in combination had an insufficient inhibitory effect on ICC xenograft rejection. "( Efficacy of immunosuppressive drugs in islet xenotransplantation: leflunomide in combination with cyclosporine and mycophenolate mofetil prevents islet xenograft rejection in the pig-to-rat model.
Groth, CG; Karlsson-Parra, A; Korsgren, O; Liu, J; Rafael, E; Sundberg, B; Wennberg, L; Zhu, S, 1997
)
0.89
"Treatment with leflunomide in vivo prevented allergen-induced mast cell degranulation in vitro because the mast cells lacked IgE on their surface."( Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma.
Eber, E; McMenamin, C; Sly, PD; Uhlig, T, 1998
)
2.08
"Treatment with leflunomide results in significantly greater improvement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression."( New and future drug therapies for rheumatoid arthritis.
Simon, LS; Yocum, D, 2000
)
0.65
"Treatment with leflunomide, an inhibitor of pyrimidine synthesis, has been shown in controlled clinical trials to produce significant clinical improvement in 50% to 60% of patients with RA and delay radiologic progression of disease."( Therapy of rheumatoid arthritis: new developments and trends.
, 1999
)
0.64

Toxicity

Leflunomide therapy appears to be effective and safe as an adjuvant drug in refractory DM with primarily cutaneous activity. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomid.

ExcerptReferenceRelevance
"0%) in the active treatment groups withdrew due to adverse events (AEs)."( Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.
Campion, G; Dimitrijevic, M; Domljan, Z; Dordevic, J; Jajic, I; Mihajlovic, D; Mladenovic, V; Popovic, M; Rozman, B; Zivkovic, M, 1995
)
0.59
" Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%)."( Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group.
Kalden, JR; Kvien, TK; Larsen, A; Loew-Friedrich, I; Oed, C; Rosenburg, R; Rozman, B; Scott, DL; Smolen, JS, 1999
)
0.9
" Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria."( Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis.
Byrne, VM; Coblyn, JS; Helfgott, SM; Kaymakcian, MV; Kremer, JM; Maier, AL; Morrell, M; Strand, V; Weinblatt, ME, 1999
)
0.76
" The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels."( A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis.
Bjorneboe, O; Breedveld, FC; Dahl, R; Dawes, PT; Emery, P; Gömör, B; Horslev-Petersen, K; Kaltwasser, JP; Lemmel, EM; Loew-Friedrich, I; Molloy, M; Nordström, D; Oed, C; Rodriguez De La Serna, A; Rosenburg, R; Tikly, M; Van Den Bosch, F, 2000
)
0.57
"Efficacy measures (including tender joint counts, swollen joint counts, assessment of functioning, Health Assessment Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological progression and treatment adverse events."( Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications.
Debroe, S; Hewitson, PJ; McBride, A; Milne, R, 2000
)
1.75
" The most common adverse effects leading to withdrawal from leflunomide treatment were gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels."( Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications.
Debroe, S; Hewitson, PJ; McBride, A; Milne, R, 2000
)
1.99
" Common adverse events with leflunomide included gastrointestinal symptoms, allergic reactions, alopecia and elevated liver enzyme levels."( Efficacy and safety of leflunomide in active rheumatoid arthritis.
Emery, P; Smolen, JS, 2000
)
0.91
" Safety measures included monitoring of adverse events and laboratory values."( The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study.
Breedveld, F; Deighton, C; Emery, P; Kalden, JR; Rozman, B; Schattenkirchner, M; Sörensen, H, 2003
)
0.62
" No new types of adverse events were observed, and liver function was normal at baseline and at the end point in the majority of patients."( The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study.
Breedveld, F; Deighton, C; Emery, P; Kalden, JR; Rozman, B; Schattenkirchner, M; Sörensen, H, 2003
)
0.62
" All adverse events were documented."( Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data.
Brin, S; de la Serna, R; Dougados, M; Emery, P; Lemmel, EM; van Riel, P; Zerbini, CA, 2003
)
0.63
" No adverse events that have not previously been seen with leflunomide were reported."( Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data.
Brin, S; de la Serna, R; Dougados, M; Emery, P; Lemmel, EM; van Riel, P; Zerbini, CA, 2003
)
0.87
" Adverse events (AEs) resulting in treatment withdrawal were higher in the 10 mg (15."( Efficacy and safety of leflunomide 10 mg versus 20 mg once daily in patients with active rheumatoid arthritis: multinational double-blind, randomized trial.
Poór, G; Strand, V, 2004
)
0.63
" A total of 34% of subjects experienced adverse events and in 6 (6."( The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis.
Cohen, S; Cooley, DA; Cush, J; Genovese, M; Hansen, KE; Patel, SR; Schiff, M; Singhal, A; Sundaramurthy, S, 2004
)
0.62
"The adverse events noted within the combination therapy group were in keeping with the known risks of each drug when used individually."( The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis.
Cohen, S; Cooley, DA; Cush, J; Genovese, M; Hansen, KE; Patel, SR; Schiff, M; Singhal, A; Sundaramurthy, S, 2004
)
0.62
"In this cohort, adverse events were not very different from those seen in patients on either treatment alone and the combination of leflunomide plus infliximab did not appear to be as badly tolerated as described in a previous study."( Safety of leflunomide plus infliximab combination therapy in rheumatoid arthritis.
Cantagrel, A; El Mahou, S; Godfrin, B; Godinho, F; Navaux, F; Zabraniecki, L,
)
0.74
" Both postmarketing surveillance and epidemiological study results are consistent with the safety profile of leflunomide reported in clinical trials, and no increased risk was observed with leflunomide, compared with other disease modifying antirheumatic drugs; these studies have allowed a more precise representation of the incidence of adverse events occurring with leflunomide under normal conditions of care."( Leflunomide: a manageable safety profile.
Breedveld, FC; Dougados, M; Emery, P; Kalden, JR; Smolen, JS; Strand, CV; van Riel, PL, 2004
)
1.98
"Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies."( Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.
Behrens, F; Falk, FG; Gladman, D; Jones, P; Kaltwasser, JP; Mease, P; Nash, P; Rosen, CF; Wollenhaupt, J, 2004
)
2.08
"Spontaneous cases of hepatic adverse events have been reported in patients with rheumatoid arthritis who were being treated with leflunomide, one of the newer disease-modifying antirheumatic drugs (DMARDs)."( Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis.
Bitton, A; Ernst, P; Hudson, M; Kezouh, A; Suissa, S, 2004
)
0.53
"To determine and compare the incidence of serious adverse events (AE) during treatment of rheumatoid arthritis (RA) with disease modifying antirheumatic drugs (DMARD), focusing on leflunomide (LEF)."( Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study of leflunomide compared with other DMARD.
Cannon, GW; Dai, W; Holden, WL; Juhaeri, J; Scarazzini, L; Stang, P, 2004
)
0.74
" Every 3 months data were collected regarding disease activity (DAS28), adverse events and treatment changes."( The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.
Creemers, MC; Flendrie, M; van Riel, PL; Welsing, PM, 2005
)
0.59
" No differences in drug survival, disease activity or adverse events were observed between the groups."( The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.
Creemers, MC; Flendrie, M; van Riel, PL; Welsing, PM, 2005
)
0.59
"The results indicate that the administration of infliximab after or simultaneously with leflunomide is safe and efficacious in RA patients."( The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.
Creemers, MC; Flendrie, M; van Riel, PL; Welsing, PM, 2005
)
0.81
" Five patients withdrew because of failure to maintain efficacy, 2 withdrew their consent, and 1 withdrew because of an adverse event."( Long-term open-label preliminary study of the safety and efficacy of leflunomide in patients with polyarticular-course juvenile rheumatoid arthritis.
Duffy, C; Goldsmith, D; Hawkins, D; Howard, P; Petty, R; Schanberg, L; Silverman, E; Spiegel, L; Strand, V, 2005
)
0.56
"6 months), 16% for secondary loss of efficacy (median = 7 months), and 32% for the occurrence of an adverse event (half within 4 months)."( Effectiveness and safety profile of leflunomide in rheumatoid arthritis: actual practice compared with clinical trials.
Bégaud, B; Bentaberry, F; Dehais, J; Dumoulin, C; Haramburu, F; Martin, K; Schaeverbeke, T,
)
0.41
" Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups."( A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.
Bar-Or, A; Confavreux, C; Freedman, MS; Li, D; O'Connor, PW; Paty, DW; Rice, GP; Scheyer, R; Stewart, JA, 2006
)
0.33
" Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed."( Safety of infliximab used in combination with leflunomide or azathioprine in daily clinical practice.
Brocq, O; Cantagrel, A; Combe, B; Debiais, F; Deslandre, CJ; Kara-Terki, R; Kuntz, JL; Loet, XL; Mariette, X; Pavy, S; Perdriger, A, 2006
)
0.59
" Leflunomide, though effective, was associated with adverse events and has not been extensively studied in the Indian population."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
1.55
"The primary endpoint in the improvement in EULAR criteria and secondary endpoints were patient and physician global evaluation, incidence of remission and biochemical and clinical adverse events."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
0.64
" Adverse events were observed in 15, discontinuation in 5 and 24 dropped out."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
0.64
"If regular monitoring of hepatic function and hematological parameters are performed, leflunomide is an effective and safe drug in the Indian population in resistant rheumatoid arthritis patients, especially if used alone."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
0.87
" Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events."( A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis.
Choy, EH; Ravindran, V; Scott, DL, 2008
)
0.35
" The primary end point was steroid-free remission, and secondary end points were changes in the Crohn's disease activity index (CDAI) and steroid intake, responsiveness of arthralgias and adverse events."( Treatment of Crohn's disease with leflunomide as second-line immunosuppression : a phase 1 open-label trial on efficacy, tolerability and safety.
Galle, PR; Gerts, AL; Holtmann, MH; Neurath, MF; Weinman, A, 2008
)
0.63
"Acetaminophen (APAP) is safe at therapeutic levels but causes liver injury via N-acetyl-p-benzoquinone imine (NAPQI)-induced oxidative stress when overdose."( Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine.
Chan, EC; New, LS; Tan, SC, 2008
)
0.59
" The primary end point was the percentage of patients with adverse events that led to patient withdrawal and were at least possibly related to treatment."( Combination treatment with infliximab and leflunomide in patients with active rheumatoid arthritis: safety and efficacy in an open-label clinical trial.
Antoni, C; Burmester, GR; Kalden, JR; Krüger, K; Nüsslein, HG; Wollenhaupt, J,
)
0.4
"5%) withdrew due to treatment-related adverse events."( Combination treatment with infliximab and leflunomide in patients with active rheumatoid arthritis: safety and efficacy in an open-label clinical trial.
Antoni, C; Burmester, GR; Kalden, JR; Krüger, K; Nüsslein, HG; Wollenhaupt, J,
)
0.4
"The combination of infliximab and leflunomide neither increased the rate of toxicities nor resulted in unexpected adverse events."( Combination treatment with infliximab and leflunomide in patients with active rheumatoid arthritis: safety and efficacy in an open-label clinical trial.
Antoni, C; Burmester, GR; Kalden, JR; Krüger, K; Nüsslein, HG; Wollenhaupt, J,
)
0.67
"3%) discontinued the drug because of adverse effects (one patient withdrew because of both inefficacy and adverse effects)."( Leflunomide treatment in elderly patients with rheumatoid or psoriatic arthritis: retrospective analysis of safety and adherence to treatment.
Alivernini, S; Ferraccioli, G; Mazzotta, D; Zoli, A, 2009
)
1.8
"Immunosuppressants are among the pharmacological agents with the greatest potential to cause adverse reactions, although induction of hepatotoxicity is paradoxical from the pathogenic point of view, since the response of the innate and acquired immune system is a key element in the chain of events leading to chemical liver damage."( [Hepatotoxicity induced by new immunosuppressants].
Andrade, RJ; Cotta, J; Lucena, MA; Robles, M; Toscano, E, 2010
)
0.36
"Combining intra-articular corticosteroid and anti-TNF agent has proved to be safe in our cohort of patients."( Efficacy and safety of combining intra-articular methylprednisolone and anti-TNF agent to achieve prolonged remission in patients with recurrent inflammatory monoarthritis.
Haroon, M; O'Gradaigh, D, 2010
)
0.36
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."( Developing structure-activity relationships for the prediction of hepatotoxicity.
Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010
)
0.36
" In both treatment groups, the most common reason for withdrawal during the treatment was adverse events."( Leflunomide or methotrexate? Comparison of clinical efficacy and safety in low socio-economic rheumatoid arthritis patients.
Hameed, K; Ishaq, M; Mirza, AI; Muhammad, JS, 2011
)
1.81
" These data demonstrate that the parent forms of leflunomide and A77 1726 are more toxic to hepatocytes than their poorly characterized metabolites, indicating that the metabolic process of leflunomide is a detoxification step rather than an initiating event leading to toxicity."( Hepatic cytochrome P450s attenuate the cytotoxicity induced by leflunomide and its active metabolite A77 1726 in primary cultured rat hepatocytes.
Greenhaw, J; Salminen, WF; Shi, Q; Yang, X, 2011
)
0.86
"The combination of MTX and LEF in RA patients is generally safe and well tolerated."( Liver toxicity is rare in rheumatoid arthritis patients using combination therapy with leflunomide and methotrexate.
Alves, JA; Castro, GR; Fialho, SC; Morato, EF; Neves, FS; Pereira, IA; Ribeiro, GG; Zimmermann, AF,
)
0.35
" Safety assessment included monitoring of adverse events and laboratory test results."( The efficacy and safety of leflunomide in patients with active rheumatoid arthritis.
Gworys, B; Jankowski, T; Jeka, S; Karmowski, A; Karmowski, M; Kolossa, K; Wiacek, R,
)
0.43
"The most commonly observed adverse events were related to the gastrointestinal tract (i."( The efficacy and safety of leflunomide in patients with active rheumatoid arthritis.
Gworys, B; Jankowski, T; Jeka, S; Karmowski, A; Karmowski, M; Kolossa, K; Wiacek, R,
)
0.43
" The most significant adverse event was elevation of transaminases in eight patients (26%)."( Therapeutic efficacy and safety of methotrexate + leflunomide in Colombian patients with active rheumatoid arthritis refractory to conventional treatment.
Cubidez, MF; Guzman, C; Londono, J; Santos, AM; Santos, PI; Valle-Oñate, R, 2012
)
0.63
"The combination of MTX and LEF was well tolerated, with adverse events comparable to those of monotherapy and the other nonbiologic disease-modifying antirheumatic drug treatment group."( The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.
Arnold, M; Bird, P; Burnet, S; de Jager, J; Griffiths, H; Littlejohn, G; Nicholls, D; Roberts, L; Scott, J; Tymms, K; Zochling, J, 2013
)
0.63
" Adverse events occurred in 53."( Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen.
Bolosiu, H; Cutolo, M; Perdriset, G, 2013
)
0.7
" No incremental benefit was observed with the use of a loading dose, which may be associated with an increased initial rate of adverse events."( Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen.
Bolosiu, H; Cutolo, M; Perdriset, G, 2013
)
0.7
" During the treatment, 8 patients had adverse effects which could be well tolerated."( Efficacy and safety of leflunomide in treatment of steroid-dependent and steroid-resistant adult onset minimal change disease.
Huang, J; Li, J; Liu, G; Xu, R; Zhang, Y; Zhou, J, 2013
)
0.7
"Leflunomide is a relatively safe drug, with proven efficacy in RA management."( Safety evaluation of leflunomide in rheumatoid arthritis.
Conaghan, PG; Keen, HI; Tett, SE, 2013
)
2.15
" No serious adverse events were observed."( Leflunomide plus oral prednisone in treatment of idiopathic membranous nephropathy: a retrospective clinical study of efficacy and safety.
Lu, W; Xie, L; Xue, W; Yang, S; Yin, A, 2013
)
1.83
" There was no serious adverse events during the study."( Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi-center study.
Bi, LQ; Chen, LN; Fang, YF; Gu, F; Guo, JL; Hao, YJ; Li, R; Li, XF; Li, ZG; Liu, HX; Liu, XY; Luo, Y; Mei, YF; Ren, LM; Su, Y; Sun, LY; Zhang, ZL; Zhang, ZY; Zhao, JX; Zhu, P, 2016
)
0.72
" The proportions of all adverse events were comparable in the two groups except for diarrhea."( Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.
Chen, Z; Li, XM; Li, XP; Li, ZG; Su, Y; Xiang, N; Yang, M; Zhang, MJ; Zhao, DB; Zhu, P; Zuo, XX, 2015
)
0.64
" Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients."( Safety and retention of combination triple disease-modifying anti-rheumatic drugs in new-onset rheumatoid arthritis.
Cummins, L; Duggan, E; Katikireddi, VS; Pahau, H; Shankaranarayana, S; Su, KY; Thomas, R; Videm, V, 2015
)
0.42
"Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites."( Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
Jones, LH; Nadanaciva, S; Rana, P; Will, Y, 2016
)
0.43
" Patients were dependent on glucocorticoid and refractory to at least two full-dose immunosuppressants/immunomodulators or presented previous adverse events with immunobiological drugs."( Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.
de Souza, FHC; de Souza, RC; Miossi, R; Shinjo, SK,
)
0.44
"Leflunomide proved effective and safe in 12 (66."( Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.
de Souza, FHC; de Souza, RC; Miossi, R; Shinjo, SK,
)
1.88
"Leflunomide therapy appears to be effective and safe as an adjuvant drug in refractory DM with primarily cutaneous activity."( Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.
de Souza, FHC; de Souza, RC; Miossi, R; Shinjo, SK,
)
1.88
" Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide."( Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey.
Eurich, DT; Hall, JJ; Katz, SJ; Keeling, SO; Maksymowych, WP; Schultz, M, 2017
)
0.95
" Serious adverse events were similar."( Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial.
de Silva, R; Fernandopulle, R; Galappatthy, P; Hart, M; Kelleher, P; Saravanamuttu, U; Senerath, U; Seneviratne, SL; Udagama, P; Weerasekera, LP; Wijayaratne, LS; Wijesinghe, H, 2017
)
1.9
" Data that were extracted from the medical records included signalment, body weight, underlying indication for leflunomide, dosage of leflunomide, treatment duration, concurrent medications, treatment response, and adverse events."( A Retrospective Study on the Safety and Efficacy of Leflunomide in Dogs.
Lappin, MR; Legare, M; Sato, M; Veir, JK, 2017
)
0.92
" Inhibiting JNK activation using a JNK inhibitor attenuated the ER stress and cytotoxicity of leflunomide, whereas inhibiting ERK1/2 using an ERK1/2 inhibitor or ERK1/2 siRNA increased the adverse effect caused by leflunomide, suggesting opposite roles for the two pathways."( Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells.
Chen, S; Couch, L; Guo, L; Ning, B; Qing, T; Ren, Z; Shi, L; Xuan, J; Yu, D, 2017
)
0.9
" Data were extracted for ACR20/50, HAQ-DI, SF-36 and adverse/serious adverse events after 16-24 weeks."( Efficacy and safety of systemic treatments in psoriatic arthritis: a systematic review, meta-analysis and GRADE evaluation.
Dressler, C; Eisert, L; Nast, A; Pham, PA, 2019
)
0.51
" There was a greater number of adverse events in the LEF + MTX group (66 in LEF + MTX and 49 in TAC + MTX)."( Efficacy and safety of add-on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate.
Baek, HJ; Cha, HS; Choi, IA; Jun, JB; Kang, SW; Kang, YM; Lee, YJ; Park, SH; Shin, K; Song, YW, 2019
)
0.77
" Commonly reported adverse effects include diarrhea, nausea, hepatotoxicity, hypertension, and transient global hair loss; however, additional side effects may be associated with the medication not reported in the monograph."( Reversible alopecia areata: a little known side effect of leflunomide.
Cusnir, I; Hall, J; Koller, G; Ye, C, 2019
)
0.76
" Other effectiveness evaluations included those of adverse events, quality of life including functional status (Health Assessment Questionnaire [HAQ] total score), and a quality-of-life instrument for dermatologic diseases (Dermatology Life Quality Index [DLQI] total score)."( Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysis.
Dai, Q; Xu, L; Yu, X, 2019
)
0.82
"Leflunomide is an effective and well-tolerated treatment for PsA, and would be a safe and convenient option."( Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysis.
Dai, Q; Xu, L; Yu, X, 2019
)
2.27
" Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement."( Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis.
Aalto, K; Backström, M; Grönlund, MM; Kröger, L; Markula-Patjas, K; Putto-Laurila, A; Remes-Pakarinen, T; Vähäsalo, P, 2020
)
0.56
" Clinical manifestation, IgG4-RD responder index (IgG-RD RI), serological indexes, gland ultrasound findings, and adverse drug effect were recorded."( Efficacy and safety of iguratimod on patients with relapsed or refractory IgG4-related disease.
Bian, W; Chen, D; Chen, J; Fu, J; Li, Y; Li, Z; Liu, Y; Sun, X; Zhang, W; Zhang, Y; Zhao, X, 2020
)
0.56
" Safety was evaluated from treatment-emergent adverse events (TEAEs)."( Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study.
Chohan, S; Chou, RC; Fructuoso, FJG; Gottlieb, A; Luggen, ME; Mease, PJ; Mendelsohn, AM; Rahman, P; Raychaudhuri, SP; Rozzo, SJ, 2021
)
0.62
" Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration."( Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors "leflunomide" and "teriflunomide" in Covid-19: A narrative review.
Avti, P; Bhattacharyya, A; Chhimpa, N; Kaur, H; Kumar, S; Medhi, B; Prajapat, M; Prakash, A; Sarma, P; Sharma, S; Singh, A; Singh, R; Thota, P, 2021
)
1.15
"The clinical efficacy and safety of leflunomide and methotrexate are evaluated by American College of Rheumatology (ACR)20/50/70, DAS28, total effective rate, adverse reaction rate, morning stiffness, swollen joint count, tender joint count, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor."( Clinical efficacy and safety of methotrexate compared with leflunomide in the treatment of rheumatoid arthritis: A protocol for systematic review and meta-analysis.
Cao, J; Li, X; Qi, W; Xia, Y, 2021
)
1.14
" Side-effect prevalence was higher in the LEF group (11 (31."( Efficacy and safety of tofacitinib versus leflunomide with glucocorticoids treatment in Takayasu arteritis: A prospective study.
Chen, H; Dai, X; Ding, Z; Ji, Z; Jiang, L; Jin, X; Kong, X; Ma, L; Wang, J; Wu, S, 2022
)
0.99
" Adverse events were observed in 8% of patients (0."( Efficacy and safety of leflunomide in the management of large vessel vasculitis: A systematic review and metaanalysis of cohort studies.
Brugarolas, E; Estrada, P; LLop, D; Maymó-Paituvi, P; Narváez, J; Nolla, JM; Palacios-Olid, J; Vidal-Montal, P, 2023
)
1.22
" Clinical data at baseline and after treatment, treatment response, relapse rate, and adverse effects were recorded and analyzed."( Comparison of the efficacy and safety of leflunomide versus mycophenolate mofetil in treating IgG4-related disease: a retrospective cohort study.
Chen, Y; Fei, Y; Li, J; Li, R; Liu, Z; Lu, H; Luo, X; Peng, L; Peng, Y; Wu, T; Zeng, X; Zhang, W; Zhao, Y; Zhou, J, 2023
)
1.18
" Moreover, more patients in group I had adverse effects compared with group II (36."( Comparison of the efficacy and safety of leflunomide versus mycophenolate mofetil in treating IgG4-related disease: a retrospective cohort study.
Chen, Y; Fei, Y; Li, J; Li, R; Liu, Z; Lu, H; Luo, X; Peng, L; Peng, Y; Wu, T; Zeng, X; Zhang, W; Zhao, Y; Zhou, J, 2023
)
1.18
" Some drugs are more toxic than others."( Comparative analysis of multiorgan toxicity induced by long term use of disease modifying anti-rheumatic drugs.
Iqbal, MA; Mumtaz, T; Tahir, A; Tariq, MA, 2023
)
0.91

Pharmacokinetics

The two leflunomide formulations showed similar pharmacokinetic profiles in terms of A77 1726. The test formulation was found to be bioequivalent to the reference formulation. Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel ester.

ExcerptReferenceRelevance
" Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria."( Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis.
Byrne, VM; Coblyn, JS; Helfgott, SM; Kaymakcian, MV; Kremer, JM; Maier, AL; Morrell, M; Strand, V; Weinblatt, ME, 1999
)
0.76
" No significant pharmacokinetic interactions between leflunomide and methotrexate were noted."( Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis.
Byrne, VM; Coblyn, JS; Helfgott, SM; Kaymakcian, MV; Kremer, JM; Maier, AL; Morrell, M; Strand, V; Weinblatt, ME, 1999
)
0.78
" These novel techniques not only are illuminating the 'black box' that has obscured the pharmacodynamic effects of immunosuppressants but also are uncovering new mechanisms of action of these drugs."( Pharmacodynamics of immunosuppressive drugs.
Dambrin, C; Klupp, J; Morris, RE, 2000
)
0.31
" The pharmacokinetic results showed that it exhibited first order kinetic characteristics."( Pharmacokinetics of leflunomide in Chinese healthy volunteers.
Jin, Y; Li, CY; Li, J; Li, YH; Xu, SY; Yao, HW; Zhang, YF, 2002
)
0.64
" It has a long elimination half-life (approximately 2 weeks), reaching a steady state after approximately 20 weeks."( Clinical pharmacokinetics of leflunomide.
Rozman, B, 2002
)
0.61
" Blood for pharmacokinetic analysis was obtained during the first cycle."( Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101.
Adamson, PC; Balis, FM; Blaney, SM; Cropp, GF; Gillespie, AF; Hannah, AL; Kitchen, B; Murphy, RF; Patel, M; Whitcomb, PG; Widemann, BC, 2004
)
0.32
"19 l/day per m(2) and its terminal elimination half-life was 14 days."( Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101.
Adamson, PC; Balis, FM; Blaney, SM; Cropp, GF; Gillespie, AF; Hannah, AL; Kitchen, B; Murphy, RF; Patel, M; Whitcomb, PG; Widemann, BC, 2004
)
0.32
" A steady-state infusion model best described the pharmacokinetic data."( Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis.
Chan, V; Charles, BG; Tett, SE, 2005
)
0.53
" Data from two clinical studies were used to establish a population pharmacokinetic (PPK) model for the active metabolite (M1) of leflunomide in patients with juvenile rheumatoid arthritis (JRA) and determine appropriate pediatric doses."( Population pharmacokinetics of the active metabolite of leflunomide in pediatric subjects with polyarticular course juvenile rheumatoid arthritis.
Bhargava, VO; Kovacs, SJ; Ludden, TM; Shi, J; Wang, Y, 2005
)
0.78
" A population pharmacokinetic model was developed to estimate the oral clearance (CL/F) and volume of distribution (V/F)."( Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis.
Bohanec Grabar, P; Dolzan, V; Grabnar, I; Logar, D; Mrhar, A; Peterlin Masic, L; Rozman, B; Suput, D; Tomsic, M; Trdan, T, 2009
)
0.55
" We compared the pharmacokinetic characteristics of two leflunomide formulations in healthy subjects and assessed whether these formulations were bioequivalent."( Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study.
Kim, KA; Lee, GH; Lee, YH; Park, JY; Park, SW; Ryu, JH, 2010
)
0.86
"After administering a single dose of 20 mg of each leflunomide formulation, the mean AUC(0-t) and Cmax values of A771726 were 487."( Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study.
Kim, KA; Lee, GH; Lee, YH; Park, JY; Park, SW; Ryu, JH, 2010
)
0.86
"The two leflunomide formulations showed similar pharmacokinetic profiles in terms of A77 1726, and the test formulation was found to be bioequivalent to the reference formulation with respect to the rate and extent of leflunomide absorption."( Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study.
Kim, KA; Lee, GH; Lee, YH; Park, JY; Park, SW; Ryu, JH, 2010
)
1.04
" This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations."( Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection.
Baliga, P; Bratton, C; Chavin, K; Krisl, JC; McGillicuddy, J; Pilch, N; Taber, DJ; Thomas, B, 2012
)
2.03
" Plasma teriflunomide (active metabolite of leflunomide) concentrations were determined, and pharmacokinetic parameters were calculated."( Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean healthy volunteers.
Kim, EY; Kim, HS; Lim, YJ; Moon, BS; Oh, M; Shim, EJ; Shin, JG; Shon, JH; Song, GS, 2013
)
0.9
" However, the utility of clinical pharmacokinetic monitoring for leflunomide is as yet unclear."( Clinical Pharmacokinetic Monitoring of Leflunomide in Renal Transplant Recipients with BK Virus Reactivation: A Review of the Literature.
Ensom, MHH; Leung, M; Ng, JCY; Wright, AJ, 2017
)
0.96
"Based on a pharmacokinetic (PK) study assessing the relative bioavailability of teriflunomide sodium compared to leflunomide, a population pharmacokinetic (Pop PK) analysis was firstly conducted using non-linear mixed effect model."( A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.
Chen, X; Hu, P; Jiang, J; Liu, D; Wu, Y; Yao, X, 2019
)
0.72
"Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel ester derivative of paeoniflorin, which has been shown to have synergistic pharmacodynamic effects with leflunomide (LEF)."( Effects of paeoniflorin-6'-O-benzene sulfonate on the pharmacokinetics, excretion and tissue distribution of leflunomide in rats.
Gao, J; Kuai, J; Wang, C; Wang, Q; Wei, W; Xiao, F; Xiao, N; Xu, Z, 2022
)
1.13

Compound-Compound Interactions

The treatment with Valsartan combined with Clopidogrel and Leflunomide can reduce the urinary proteins loss and renal function deterioration for IgA nephropathy patients.

ExcerptReferenceRelevance
" A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat."( Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.
Bartlett, RR; Coupland, SE; Hoffmann, F; Karow, AC; Krause, L; Lehmann, M, 1995
)
0.5
" We investigated whether RS61443 in combination with leflunomide (Lef) or FK506 (FK) could prolong allograft survival in a rat heart model, since combination therapy might help to overcome drug toxicity."( Effect of RS61443 in combination with leflunomide or FK506 on rat heart allograft survival.
Antoniou, E; D'Silva, M; DeRoover, A; Howie, AJ; McMaster, P; Nishimura, Y, 1996
)
0.81
" In order to develop new drug combinations for immunotherapy, we tested the effects of PTX in combination with RAP or A77 1726 (the active metabolite of leflunomide) on in vitro T cell activation in a mouse model system."( Inhibition of anti-CD3 antibody-induced mouse T cell activation by pentoxifylline in combination with rapamycin or A77 1726 (leflunomide).
Hoskin, DW; Richard, M,
)
0.54
"Long-term survival of hamster liver and heart xenografts in Lewis rats could be induced by a regimen of short-term FK506 in combination with Lef followed by FK506 monotherapy."( FK506 treatment in combination with leflunomide in hamster-to-rat heart and liver xenograft transplantation.
Blinder, L; Chong, AS; Foster, P; Ma, LL; Sankary, HN; Shen, JK; Williams, JW; Yin, DP, 1998
)
0.58
" Currently, SU101 in combination with cytotoxic agents is in late-stage clinical development for the treatment of cancers."( Effects of SU101 in combination with cytotoxic agents on the growth of subcutaneous tumor xenografts.
Cherrington, JM; Kabbinavar, F; Mann, E; Schwartz, DP; Shawver, LK; Slamon, DJ; Strawn, LM, 2000
)
0.31
"To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis."( The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis.
Cohen, S; Cooley, DA; Cush, J; Genovese, M; Hansen, KE; Patel, SR; Schiff, M; Singhal, A; Sundaramurthy, S, 2004
)
0.89
"To investigate the anti-inflammatory effects of the active leflunomide metabolite A771726 (Lef-M) in combination with methotrexate (MTX) on synovial macrophages (SM) from rheumatoid arthritis (RA) patients co-cultured with an activated T cell line (Jurkat cell line)."( Anti-inflammatory effects of leflunomide in combination with methotrexate on co-culture of T lymphocytes and synovial macrophages from rheumatoid arthritis patients.
Capellino, S; Cutolo, M; Montagna, P; Seriolo, B; Sulli, A; Villaggio, B, 2006
)
0.87
"Pro-inflammatory cytokines (TNFalpha, IL1beta, IL6), adhesion molecule ICAM-1, cyclooxygenase isoenzymes (COX1, COX2), and the nuclear factor kappaB (NF-kappaB) complex were analysed on SM co-cultured with a T cell line, as intracellular protein expression by immunocytochemistry (ICC) and western blot analysis, as extracellular protein expression by ELISA assay, and as mRNA expression by reverse transcriptase-multiplex PCR (RT-MPCR) after treatment with Lef-M (1, 10, 30 micromol/l) alone or in combination with MTX (50 ng/ml)."( Anti-inflammatory effects of leflunomide in combination with methotrexate on co-culture of T lymphocytes and synovial macrophages from rheumatoid arthritis patients.
Capellino, S; Cutolo, M; Montagna, P; Seriolo, B; Sulli, A; Villaggio, B, 2006
)
0.63
"A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period."( Safety of infliximab used in combination with leflunomide or azathioprine in daily clinical practice.
Brocq, O; Cantagrel, A; Combe, B; Debiais, F; Deslandre, CJ; Kara-Terki, R; Kuntz, JL; Loet, XL; Mariette, X; Pavy, S; Perdriger, A, 2006
)
0.59
" INF was used in combination with LEF in 171 patients and with AZA in 54."( Safety of infliximab used in combination with leflunomide or azathioprine in daily clinical practice.
Brocq, O; Cantagrel, A; Combe, B; Debiais, F; Deslandre, CJ; Kara-Terki, R; Kuntz, JL; Loet, XL; Mariette, X; Pavy, S; Perdriger, A, 2006
)
0.59
"Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations."( Safety of infliximab used in combination with leflunomide or azathioprine in daily clinical practice.
Brocq, O; Cantagrel, A; Combe, B; Debiais, F; Deslandre, CJ; Kara-Terki, R; Kuntz, JL; Loet, XL; Mariette, X; Pavy, S; Perdriger, A, 2006
)
0.59
"Determination of safety and efficacy of leflunomide alone and if not useful, in combination with methotrexate in patients refractory to conventional disease-modifying agents."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
0.91
"Open labeled clinical trial with leflunomide [100 mg, OD x 3 days followed by 20 mg, OD x 6 months], if no improvement at three months, combined with methotrexate [5-7."( Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.
Antony, T; Jose, VM; Paul, BJ; Thomas, T, 2006
)
0.93
"To investigate the effects and safety of leflunomide combined with hormone therapy for refractory IgA nephropathy."( [Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy].
Liu, ZR; Rong, L, 2007
)
0.98
"Leflunomide combined with hormone therapy can be one of the safety and effective choices for treatment of refractory IgA nephropathy."( [Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy].
Liu, ZR; Rong, L, 2007
)
2.16
" Leflunomide, compared with cyclophosphamide, in combination with prednisone was effective in the induction therapy of proliferative lupus nephritis and was generally well-tolerated."( Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study.
Cai, GY; Chen, XM; Cui, TG; Hou, FF; Jiang, ZP; Li, YN; Lu, FM; Mei, CL; Ni, ZH; Qian, JQ; Wang, GB; Wang, HY; Wang, YH; Xu, FF; Yu, XQ; Zhang, FS; Zhao, MH; Zhao, XZ; Zhu, TY; Zou, WZ, 2008
)
1.5
"Data from 1769 outpatients enrolled in the German biologics register RABBIT who were treated with one of the TNFalpha inhibitors adalimumab, etanercept, or infliximab in combination with either methotrexate (n = 1375) or leflunomide (n = 394) were included in the analysis."( Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide.
Dockhorn, R; Hierse, F; Kekow, J; Listing, J; Strangfeld, A; Tony, HP; von Hinueber, U; Zink, A, 2009
)
0.75
"The current clinical practice is to use methotrexate as a first choice for the combination with TNFalpha antagonists."( Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide.
Dockhorn, R; Hierse, F; Kekow, J; Listing, J; Strangfeld, A; Tony, HP; von Hinueber, U; Zink, A, 2009
)
0.56
" We report one patient with KD treated with leflunomide in combination with glucocorticoids and analyzed the literature on treatment of KD."( Effective treatment of Kimura's disease with leflunomide in combination with glucocorticoids.
Dai, L; Mo, YQ; Pessler, F; Wei, XN; Zhang, BY; Zheng, DH, 2011
)
0.89
"The Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis (SMILE) study was a multicenter, observational, cross-sectional, retrospective safety study."( The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.
Arnold, M; Bird, P; Burnet, S; de Jager, J; Griffiths, H; Littlejohn, G; Nicholls, D; Roberts, L; Scott, J; Tymms, K; Zochling, J, 2013
)
0.89
"The aim of this study was to evaluate the effect of treatment with methotrexate (MTX), by itself or combined with other non-biological disease-modifying antirheumatic drugs (DMARDs) (methotrexate, MTX with prednisolone, MTX with leflunomide, MTX with chloroquine, and MTX with sulfasalazine) on clinimetric outcomes in a retrospective cohort with a 6-month follow-up and under a Treat to Target (T2T) approach."( Treatment of rheumatoid arthritis with methotrexate alone and in combination with other conventional DMARDs using the T2T strategy. A cohort study.
Castro, C; de la Hoz-Valle, J; Palomino, A; Sánchez, G; Santos-Moreno, PI; Villarreal, L, 2015
)
0.6
"The treatment with Valsartan combined with Clopidogrel and Leflunomide can reduce the urinary proteins loss and renal function deterioration for IgA nephropathy patients and cause minimal adverse reactions."( Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy.
Chen, F; Cheng, G; Fang, Y; Guo, Y; Li, H; Liu, D; Liu, F; Liu, L; Liu, Z; Margetts, P; Tang, L; Zhao, Z, 2015
)
0.92
" We found that treatment with As2 O3 combined with leflunomide can significantly prolong the survival of heart xenograft by inhibiting Th1 and Th2 differentiation and reducing the production of IgG and IgM."( As2 O3 combined with leflunomide prolongs heart xenograft survival via suppressing the response of Th1, Th2, and B cells in a rat model.
Cheng, LN; Fu, JZ; Jiao, ZX; Jin, N; Leng, Y; Ni, SB; Qi, ZQ; Wang, JH; Wu, HQ; Xia, JJ, 2016
)
1.01
"LEF combined with prednisone has a certain efficacy on the RNS and displays few adverse reactions."( Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome.
Chen, W; Liu, L; Liu, Y; Qu, X; Zhang, Y, 2016
)
0.81
" In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination."( Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial.
de Silva, R; Fernandopulle, R; Galappatthy, P; Hart, M; Kelleher, P; Saravanamuttu, U; Senerath, U; Seneviratne, SL; Udagama, P; Weerasekera, LP; Wijayaratne, LS; Wijesinghe, H, 2017
)
2.09
"We prospectively enrolled 215 newly diagnosed patients with IgG4-RD, who were initially treated with glucocorticoid (GC) alone or in combination with immunosuppressive agents (IM), and had at least 6 months of follow up."( Failure of remission induction by glucocorticoids alone or in combination with immunosuppressive agents in IgG4-related disease: a prospective study of 215 patients.
Fei, Y; Feng, R; Lai, Y; Peng, L; Wang, L; Wang, M; Zeng, X; Zhang, F; Zhang, P; Zhang, W; Zhang, X; Zhao, Y, 2018
)
0.48
" This study compared groups treated with high-dose methotrexate (MTX)/leflunomide (LEF) and CP-25 combined with low-dose MTX/LEF in an adjuvant-induced arthritis (AA) rat model and investigated possible mechanisms."( CP-25 combined with MTX/ LEF ameliorates the progression of adjuvant-induced arthritis by the inhibition on GRK2 translocation.
Chang, Y; Jia, X; Wang, C; Wei, W; Wu, Y; Yang, X; Zhang, L; Zhao, Y, 2019
)
0.75
"LEF and/or MTX combined with GPS ameliorated oxidative stress by increasing the mRNA levels of the antioxidant gene Nrf2, GCLC, HO-1, and NQO1, increasing the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), reducing the oxidant substance malondialdehyde (MDA), reducing the inflammatory response by decreasing the mRNA levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and inhibiting the secretion of the pro-inflammatory cytokines TNFα, IL-6, IL-1β and reducing C-reactive protein (CRP), as well as alleviating the external symptoms of arthritis."( Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats.
Li, H; Li, M; Li, X; Liu, J; Liu, Q; Wan, Z; Wang, R; Wu, X; Zhao, H, 2021
)
0.86
"This study evaluated the clinical efficacy of leflunomide combined with low-dose prednisone (0."( Clinical evaluation of efficacy of leflunomide combined with low-dose prednisone for treatment of myasthenia gravis.
Chen, J; Huang, X; Liu, W; Lu, Y; Ou, C; Qiu, L; Ran, H; Yang, W, 2023
)
1.45
"To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN)."( Huangkui Capsule in Combination with Leflunomide Improves Immunoglobulin A Nephropathy by Inhibiting the TGF-β1/Smad3 Signaling Pathway.
Li, Y; Pei, S, 2021
)
1.11
" We administered tofacitinib combined with leflunomide to a 38-year-old female patient who presented with PsA and IgA nephropathy."( Tofacitinib combined with leflunomide for treatment of psoriatic arthritis with IgA nephropathy: a case report with literature review.
Ci, X; Du, X; Li, L; Lu, X; Luo, M; Wu, L; Xue, H, 2022
)
1.28
"Diabetic kidney disease (DKD) combined with Membranous Nephropathy (MN) was observed in some patients with the increasing of Diabetic patients."( Retrospective analysis of leflunomide and low-dose methylprednisolone for the treatment of diabetic nephropathy combined with membranous nephropathy.
Cui, S; Li, P; Li, Q; Li, W; Shang, S; Wang, C; Wang, W, 2022
)
1.02
"In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored."( Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators.
Jiang, F; Liu, H; Xing, X; Zhang, M; Zheng, K; Zhou, C, 2023
)
1.41
"Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function."( Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators.
Jiang, F; Liu, H; Xing, X; Zhang, M; Zheng, K; Zhou, C, 2023
)
1.43

Bioavailability

The bioavailability after a single oral dose of leflunomide was 100%. The study was based on a pharmacokinetic (PK) study.

ExcerptReferenceRelevance
" Identical areas under the curve suggest bioavailability was 100% (AUCp."( Blood distribution and single-dose pharmacokinetics of leflunomide.
Dias, VC; LeGatt, DF; Lucien, J; Yatscoff, RW, 1995
)
0.54
" The bioavailability after a single oral dose of leflunomide was 100%."( Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats.
Chen, YJ; Craigmill, A; Gregory, CR; Kyles, AE; Mehl, ML; Tell, L, 2012
)
0.88
" Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource-poor setting, is economical."( Leflunomide for cytomegalovirus: bench to bedside.
Chacko, B; John, GT, 2012
)
1.82
" However, no published data is available regarding the bioavailability of this in the Indian population."( Comparative bioequivalence study of leflunomide tablets in Indian healthy volunteers.
Agarwal, S; Chattaraj, TK; Das, A; Ghosh, D; Pal, TK; Sarkar, AK, 2012
)
0.65
"Based on a pharmacokinetic (PK) study assessing the relative bioavailability of teriflunomide sodium compared to leflunomide, a population pharmacokinetic (Pop PK) analysis was firstly conducted using non-linear mixed effect model."( A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.
Chen, X; Hu, P; Jiang, J; Liu, D; Wu, Y; Yao, X, 2019
)
0.72
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

The progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60. Substituting leflinomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy.

ExcerptRelevanceReference
" Drug studies were performed, using a 4-day dosing schedule, on optimal DTH elicited on day 10, suboptimal DTH elicited on day 15, and AA (day 16)."( Drug actions on delayed-type hypersensitivity in rats with developing and established adjuvant arthritis.
Hambleton, P; McMahon, S, 1990
)
0.28
"), dosed for 8 or 16 days beginning with the day of adjuvant administration, significantly reduced edema, fibrinogen levels, and erythrocyte sedimentation rates (ESR) 42 days later."( Disease modifying activity of HWA 486 in rat adjuvant-induced arthritis.
Buyniski, JP; Gylys, JA; Pasternak, RD; Siminoff, P; Wadopian, NS; Wright, RN, 1987
)
0.27
" However, the progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60."( Pharmacologically induced regression of chronic transplant rejection.
Chong, A; Foster, P; Jensik, S; McChesney, L; Mital, D; Sankary, H; Shen, J; Short, J; Xiao, F; Yang, J, 1995
)
0.5
"Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo."( Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.
Campion, G; Dimitrijevic, M; Domljan, Z; Dordevic, J; Jajic, I; Mihajlovic, D; Mladenovic, V; Popovic, M; Rozman, B; Zivkovic, M, 1995
)
0.59
" Such information would prove invaluable in determining the appropriate medium for analysis and optimal immunosuppressive dosing regimes."( Blood distribution and single-dose pharmacokinetics of leflunomide.
Dias, VC; LeGatt, DF; Lucien, J; Yatscoff, RW, 1995
)
0.54
"5 mg/kg/day orally) treatment initiated on day 0 was continued until complete graft rejection; the leflunomide dosage was reduced to 10 mg/kg/day after day 14 because of weight loss and leukopenia."( Leflunomide prolongs pulmonary allograft and xenograft survival.
Gandy, KL; Gutierrez, J; Hoyt, G; Morris, RE; Reitz, BA; Robbins, RC; Yuh, DD,
)
1.79
" Pulse cyclophosphamide has been shown to be as effective as the standard therapy in necrotizing vasculitides; however, an alarmingly high rate of infections was observed in this study in both arms possibly related to the high dosage of GCs."( New concepts in treatment protocols for severe systemic vasculitis.
Gross, WL, 1999
)
0.3
"5 mg/kg) were given orally by gavage; thrice weekly according to the monotherapy or dual-therapy dosing protocol."( Immunosuppressive effect of combination schedules of brequinar with leflunomide or tacrolimus on rat cardiac allotransplantation.
Antoniou, EA; Chondros, K; D'Silva, M; Deroover, A; Howie, AJ; McMaster, P, 1999
)
0.54
"To evaluate the clinical feasibility and pharmacologic behavior of the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor SU101, administered on a prolonged, intermittent dosing schedule to patients with advanced solid malignancies."( Phase I and pharmacologic study of the tyrosine kinase inhibitor SU101 in patients with advanced solid tumors.
Baker, SD; Cropp, G; Drengler, R; Eckardt, JR; Eckhardt, SG; Hammond, L; Hannah, AL; Kraynak, MA; Kuhn, JG; Moczygemba, J; Rizzo, J; Rowinsky, EK; Smith, L; Sweeney, KR; Thurman, A; Villalona-Calero, MA; Von Hoff, DD; Weiss, G, 1999
)
0.3
"An obvious dose-response relationship for the antiproliferative effects of each drug was detected."( Comparison of the in vitro antiproliferative effects of five immunosuppressive drugs on lymphocytes in whole blood from cats.
Craigmill, AL; Gregory, CR; Kyles, AE, 2000
)
0.31
" Differences between these trials included methotrexate dosing regimens, folate usage and disease duration."( Efficacy and safety of leflunomide in active rheumatoid arthritis.
Emery, P; Smolen, JS, 2000
)
0.62
"Leflunomide seems to possess substantial immune suppressive potency in renal and liver transplant recipients and may be safely dosed for more than 300 days."( Experiences with leflunomide in solid organ transplantation.
Brady, L; Chong, A; Huang, W; Jensik, S; Kottayil, A; Longstreth, J; Millis, M; Mital, D; Williams, JW, 2002
)
2.1
" The pharmacokinetics of M1 are not affected by food intake, and dosage requirements are not influenced by age or gender."( Clinical pharmacokinetics of leflunomide.
Rozman, B, 2002
)
0.61
"Patients with rheumatoid arthritis (RA) who received leflunomide (100 mg/day for 3 days, 10 mg/day or 20 mg/day thereafter) in the 2 phase III studies and who completed 2 years of treatment were offered inclusion in the open-label extension phase and were maintained on the same dosage of leflunomide."( The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study.
Breedveld, F; Deighton, C; Emery, P; Kalden, JR; Rozman, B; Schattenkirchner, M; Sörensen, H, 2003
)
0.87
"Current dosing strategies should be re-evaluated, and coping strategies for common AEs should be investigated."( Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study.
Aletaha, D; Eberl, G; Grisar, J; Kapral, T; Machold, KP; Smolen, JS; Stamm, T, 2003
)
0.61
" The relationship between induced lupus and leflunomide was confirmed by the resolution of the skin rash when the drug was stopped and its recurrence when it was reintroduced following a dose-response effect."( Lupus erythematosus with leflunomide: induction or reactivation?
Gensburger, D; Kanitakis, J; Kawashima, M; Marotte, H; Miossec, P, 2005
)
0.89
" Following a loading dose, patients initially received leflunomide at a dosage of 10 mg/1."( Long-term open-label preliminary study of the safety and efficacy of leflunomide in patients with polyarticular-course juvenile rheumatoid arthritis.
Duffy, C; Goldsmith, D; Hawkins, D; Howard, P; Petty, R; Schanberg, L; Silverman, E; Spiegel, L; Strand, V, 2005
)
0.81
"01), but this would not be clinically important in terms of dosage changes."( Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis.
Chan, V; Charles, BG; Tett, SE, 2005
)
0.53
" The marked variability in pharmacokinetics suggests a place for individualized dosing of leflunomide in RA therapy."( Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis.
Chan, V; Charles, BG; Tett, SE, 2005
)
0.75
" The mean MTX dosage at week 52 was similar in the 2 RCTs."( Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies.
Cohen, SB; Dorrier, C; Elashoff, D; Emery, P; Furst, DE; Khanna, D; Park, GS; Paulus, HE; Simpson, KM, 2005
)
0.33
" Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM)."( Treatment of renal allograft polyoma BK virus infection with leflunomide.
Atwood, W; Foster, P; Garfinkel, M; Gillen, D; Harland, R; Javaid, B; Jordan, J; Josephson, MA; Kadambi, P; Meehan, S; Millis, MJ; Sadhu, M; Thistlethwaite, RJ; Williams, J, 2006
)
1.49
" Once maximum improvement was obtained the dosage was decreased."( Disease modifying treatment for feline rheumatoid arthritis.
Hanna, FY, 2005
)
0.33
" To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation."( Leflunomide and warfarin interaction: case report and review of the literature.
Chonlahan, J; Halloran, MA; Hammonds, A, 2006
)
2
" Careful dosing and periodic monitoring of patients treated with leflunomide for possible adverse drug reaction is recommended."( Severe cutaneous adverse drug reaction to leflunomide: a report of five cases.
Betkerur, J; Kushalappa, PA; Parthasarathi, G; Savita, TG; Shastri, V,
)
0.63
" The proposed methods have been successfully applied to the analysis of leflunomide in pharmaceutical dosage forms and the results were statistically compared with that previously reported."( Spectrophotometric stability-indicating methods for the determination of leflunomide in the presence of its degradates.
Abbas, SS; Bebawy, LI; Fattah, LA; Refaat, HH,
)
0.6
"LEF at a dosage of 30 mg/day appears to be effective in the prevention of major relapses in WG, however, this is associated with an increased frequency of adverse events."( Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis.
de Groot, K; Gross, WL; Hellmich, B; Iking-Konert, C; Manger, K; Metzler, C; Miehle, N; Reinhold-Keller, E, 2007
)
0.59
" Characteristic external malformations were craniofacial defects following dosing on GD7, cleft palate on GD9, cleft palate and limb and tail deformities on GD10, and limb deformities on GD11."( Critical periods for the teratogenicity of immune-suppressant Leflunomide in mice.
Fukushima, R; Hirashiba, M; Hishikawa, A; Kanamori, S; Kaneto, M; Kitagawa, H; Muranaka, R, 2009
)
0.59
" Signalment, radiographic findings, laboratory data, dosage of leflunomide, treatment duration, treatment response, and occurrence of adverse effects were determined from medical records."( Efficacy of leflunomide for treatment of immune-mediated polyarthritis in dogs: 14 cases (2006-2008).
Baker, TA; Colopy, SA; Muir, P, 2010
)
0.98
" On the basis of findings in this study, a starting dosage for leflunomide of 3 to 4 mg/kg (1."( Efficacy of leflunomide for treatment of immune-mediated polyarthritis in dogs: 14 cases (2006-2008).
Baker, TA; Colopy, SA; Muir, P, 2010
)
0.98
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."( FDA-approved drug labeling for the study of drug-induced liver injury.
Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011
)
0.37
" From the day of arthritis onset, rats were treated daily by gavage with leflunomide (Lef) or ART at a dosage of 10 mg/kg/d or 5 mg/kg/d, respectively, for 16 days."( Inhibitory effect of the antimalarial agent artesunate on collagen-induced arthritis in rats through nuclear factor kappa B and mitogen-activated protein kinase signaling pathway.
Chen, G; Huang, H; Li, C; Li, Y; Lin, S; Lin, W; Liu, P; Shen, W; Shen, X; Wang, S; Wang, Y; Zhou, C, 2013
)
0.62
" Logistic regression showed that age at entry, the presence of DM, and daily dosage of corticosteroid were associated with development of severe infections."( Risk factors of severe infections in patients with rheumatoid arthritis treated with leflunomide.
Jeon, HS; Jun, JB; Yoo, HG; Yoo, WH; Yu, HM, 2013
)
0.61
"These results showed that some patients with RA who were taking leflunomide developed severe infections requiring hospitalization, and that older age, DM, and a higher daily dosage of corticosteroid were risk factors associated with leflunomide-associated severe infections."( Risk factors of severe infections in patients with rheumatoid arthritis treated with leflunomide.
Jeon, HS; Jun, JB; Yoo, HG; Yoo, WH; Yu, HM, 2013
)
0.85
" Leflunomide can be used for RA patients on chronic dialysis without any dosage modification."( Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study.
Bergner, R; Löffler, C; Peters, L; Schmitt, V, 2013
)
2.74
" The dosage was increased to 20 mg/day after 3 months."( Leflunomide for inflammatory arthritis in end-stage renal disease on peritoneal dialysis: a pharmacokinetic and pharmacogenetic study.
Ahern, MJ; Barbara, JA; Russo, PA; Shanahan, EM; Smith, MD; Wiese, MD, 2013
)
1.83
" The dosage and time of therapy need to be explored in the future; additional studies of large samples are needed."( BK Virus-Associated Nephropathy with Plasma Cell-Rich Infiltrates Treated by Bortezomib-Based Regimen.
Chen, JS; Cheng, DR; Ji, SM; Li, X; Liu, ZH; Wen, JQ; Wu, D; Xie, KN; Zhang, MC, 2015
)
0.42
" And it showed dosage dependent."( [Effects of leflunomide on experimental autoimmune uveitis in Lewis rats].
Fang, C; He, Y; Huang, C; Li, J; Lin, Z; Zhan, S; Zhou, D, 2015
)
0.8
" After oral dosing (15 mg/kg), the plasma exposure (AUC0-t) of leflunomide increased to 3-fold in HRN mice compared with wild type mice."( Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity.
Cao, YY; Chen, C; Lin, YF; Luan, Y; Ma, LL; Ni, X; Pan, GY; Wang, J; Wang, L; Wu, ZT; Zhang, XF, 2016
)
0.89
" The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA."( Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.
Andersen, V; Bennike, TB; Birkelund, S; Bonderup, OK; Bøgsted, M; Carlsen, TG; Christiansen, G; Ellingsen, T; Glerup, H; Meyer, MK; Stensballe, A, 2017
)
0.46
" The proposed method was successfully applied to the analysis of these drugs in dosage forms."( Bioanalytical method for the estimation of co-administered esomeprazole, leflunomide and ibuprofen in human plasma and in pharmaceutical dosage forms using micellar liquid chromatography.
Talaat, W, 2017
)
0.69
" Of the responders, 12% had used doses above 20 mg daily and 70% had used alternate daily dosing with leflunomide."( Putting recommendations into practice: Australian rheumatologists' opinions on leflunomide use in rheumatoid arthritis.
Hopkins, AM; O'Doherty, CE; Proudman, SM; Wiese, MD, 2017
)
0.9
" Data that were extracted from the medical records included signalment, body weight, underlying indication for leflunomide, dosage of leflunomide, treatment duration, concurrent medications, treatment response, and adverse events."( A Retrospective Study on the Safety and Efficacy of Leflunomide in Dogs.
Lappin, MR; Legare, M; Sato, M; Veir, JK, 2017
)
0.92
"Results suggest that the starting dosage of leflunomide should be 2 mg/kg/d rather than the currently suggested dosage of 3-4 mg/kg/d."( A Retrospective Study on the Safety and Efficacy of Leflunomide in Dogs.
Lappin, MR; Legare, M; Sato, M; Veir, JK, 2017
)
0.97
" Optimal dosing strategies in recipients with impaired kidney function remain undefined, with limited pharmacokinetic data to date."( Ganciclovir Dosing Strategies and Development of Cytomegalovirus Resistance in a Kidney Transplant Recipient: A Case Report.
Agrawal, N; Beltran, D; Echenique, IA; Najafian, N; Ramirez-Ruiz, L, 2017
)
0.46
" The highest risk of infection is associated with corticosteroids depending on the dose, so that a dosage as low as possible but stable in the perioperative period is recommended."( [Perioperative management of immunosuppressive treatment in patients undergoing joint surgery].
Krüger, K, 2017
)
0.46
" Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy."( Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report.
Chen, HA; Chen, YW; Hsu, YH; Hung, LY; Lee, CH; Wu, MS; Wu, MY, 2019
)
1.13
" In order to predict teriflunomide PK profiles for multiple dosing of teriflunomide sodium in SLE patients, a model integrating enterohepatic circulation (EHC) mechanism was utilized to simulate the teriflunomide PK profile after multiple dosing of 20 mg/day leflunomide, and compare it to the teriflunomide PK profile in a 20 mg/day leflunomide multiple dose study in rheumatoid arthritis patients."( A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.
Chen, X; Hu, P; Jiang, J; Liu, D; Wu, Y; Yao, X, 2019
)
0.69
" After this model was confirmed to capture EHC characteristics of teriflunomide in both healthy subjects and patients with rheumatoid arthritis after single and multiple dosing leflunomide, it was applied to suggest dose regimen of teriflunomide sodium in phase II study."( A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.
Chen, X; Hu, P; Jiang, J; Liu, D; Wu, Y; Yao, X, 2019
)
0.71
" The developed EHC Pop PK model exhibited the ability to predict PK profiles of teriflunomide in patients after long-term dosing and could be utilized to support phase II trial design."( A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.
Chen, X; Hu, P; Jiang, J; Liu, D; Wu, Y; Yao, X, 2019
)
0.51
"002) and less cumulative dosage of GCs was used (5103."( Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial.
Dong, C; Gao, D; Huang, F; Ji, X; Jin, J; Li, K; Li, Y; Liao, S; Luo, G; Wang, H; Wang, X; Wang, Y; Zhang, J; Zhang, Y; Zhao, Y; Zhao, Z; Zhu, J, 2020
)
0.89
" The goal of this work was to develop a population PK model for A771726 and propose an optimal individualized dosing strategy."( Development of a population pharmacokinetic model and optimal dosing regimen of leflunomide in Korean population.
Chae, D; Park, K; Shin, Y, 2023
)
1.14
" For dose optimization, simulating a set of 1000 virtual subjects from the developed model and dividing the subjects into 5 groups with WT of 50, 60, 70, 80, 90 kg, respectively, the optimal dose was explored that achieves the drug concentration most similar to the target, which was defined as the concentration for the 70 kg subject treated with the current standard dosage regimen (the loading dose of 100 mg QD for 3 days, followed by the maintenance dose of 20 mg QD)."( Development of a population pharmacokinetic model and optimal dosing regimen of leflunomide in Korean population.
Chae, D; Park, K; Shin, Y, 2023
)
1.14
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (10)

RoleDescription
non-steroidal anti-inflammatory drugAn anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins.
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
antiparasitic agentA substance used to treat or prevent parasitic infections.
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitorAn EC 1.3.98.* (oxidoreductase acting on CH-CH group of donors, with other, known, acceptors) inhibitor that interferes with the action of dihydroorotate oxidase (fumarate), EC 1.3.98.1 (formerly EC 1.3.3.1).
hepatotoxic agentA role played by a chemical compound exihibiting itself through the ability to induce damage to the liver in animals.
prodrugA compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
pyrimidine synthesis inhibitorA pathway inhibitor that inhibits the synthesis of pyrimidine.
immunosuppressive agentAn agent that suppresses immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. In addition, an immunosuppressive agent is a role played by a compound which is exhibited by a capability to diminish the extent and/or voracity of an immune response.
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitorAny EC 3.1.3.* (phosphoric monoester hydrolase) inhibitor that interferes with the action of phosphoprotein phosphatase (EC 3.1.3.16).
tyrosine kinase inhibitorAny protein kinase inhibitor that interferes with the action of tyrosine kinase.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
monocarboxylic acid amideA carboxamide derived from a monocarboxylic acid.
isoxazolesOxazoles in which the N and O atoms are adjacent.
(trifluoromethyl)benzenesAn organofluorine compound that is (trifluoromethyl)benzene and derivatives arising from substitution of one or more of the phenyl hydrogens.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (116)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
LuciferasePhotinus pyralis (common eastern firefly)Potency22.36700.007215.758889.3584AID1224835; AID588342; AID624030
acetylcholinesteraseHomo sapiens (human)Potency48.50880.002541.796015,848.9004AID1347395
glp-1 receptor, partialHomo sapiens (human)Potency14.12540.01846.806014.1254AID624417
thioredoxin reductaseRattus norvegicus (Norway rat)Potency0.63100.100020.879379.4328AID588453
phosphopantetheinyl transferaseBacillus subtilisPotency39.81070.141337.9142100.0000AID1490
hypoxia-inducible factor 1 alpha subunitHomo sapiens (human)Potency61.64483.189029.884159.4836AID1224846
RAR-related orphan receptor gammaMus musculus (house mouse)Potency1.39420.006038.004119,952.5996AID1159521; AID1159523
ATAD5 protein, partialHomo sapiens (human)Potency8.65880.004110.890331.5287AID493106; AID493107; AID504466; AID504467
Fumarate hydrataseHomo sapiens (human)Potency11.77040.00308.794948.0869AID1347053
USP1 protein, partialHomo sapiens (human)Potency31.62280.031637.5844354.8130AID504865
PPM1D proteinHomo sapiens (human)Potency18.55690.00529.466132.9993AID1347411
TDP1 proteinHomo sapiens (human)Potency4.36290.000811.382244.6684AID686978; AID686979
GLI family zinc finger 3Homo sapiens (human)Potency12.69560.000714.592883.7951AID1259368; AID1259369; AID1259392
ThrombopoietinHomo sapiens (human)Potency7.94330.02517.304831.6228AID917; AID918
AR proteinHomo sapiens (human)Potency13.11460.000221.22318,912.5098AID1259243; AID1259247; AID1259381; AID743035; AID743036; AID743042; AID743053; AID743054; AID743063
caspase 7, apoptosis-related cysteine proteaseHomo sapiens (human)Potency1.80580.013326.981070.7614AID1346978
nuclear receptor subfamily 1, group I, member 3Homo sapiens (human)Potency1.01860.001022.650876.6163AID1224838; AID1224839; AID1224893
progesterone receptorHomo sapiens (human)Potency61.13060.000417.946075.1148AID1346795
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency3.46710.01237.983543.2770AID1645841
EWS/FLI fusion proteinHomo sapiens (human)Potency16.13620.001310.157742.8575AID1259252; AID1259253; AID1259255; AID1259256
nonstructural protein 1Influenza A virus (A/WSN/1933(H1N1))Potency31.62280.28189.721235.4813AID2326
glucocorticoid receptor [Homo sapiens]Homo sapiens (human)Potency4.89660.000214.376460.0339AID720692
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency5.76330.003041.611522,387.1992AID1159552; AID1159553; AID1159555
retinoid X nuclear receptor alphaHomo sapiens (human)Potency39.15330.000817.505159.3239AID1159527; AID1159531
estrogen-related nuclear receptor alphaHomo sapiens (human)Potency2.74600.001530.607315,848.9004AID1224819; AID1224820; AID1224821; AID1224823; AID1224841; AID1224842; AID1224848; AID1224849; AID1259401; AID1259403
farnesoid X nuclear receptorHomo sapiens (human)Potency54.94100.375827.485161.6524AID743217
pregnane X nuclear receptorHomo sapiens (human)Potency4.80040.005428.02631,258.9301AID1346982; AID1346985
estrogen nuclear receptor alphaHomo sapiens (human)Potency5.75440.000229.305416,493.5996AID1259244; AID1259248; AID1259383; AID743069; AID743075; AID743080; AID743091
GVesicular stomatitis virusPotency13.80290.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency24.54540.00108.379861.1304AID1645840
polyproteinZika virusPotency11.77040.00308.794948.0869AID1347053
ParkinHomo sapiens (human)Potency1.63600.819914.830644.6684AID720573
P53Homo sapiens (human)Potency56.23410.07319.685831.6228AID504706
peroxisome proliferator-activated receptor deltaHomo sapiens (human)Potency48.96620.001024.504861.6448AID743215
vitamin D (1,25- dihydroxyvitamin D3) receptorHomo sapiens (human)Potency20.68310.023723.228263.5986AID743222; AID743241
arylsulfatase AHomo sapiens (human)Potency37.93301.069113.955137.9330AID720538
pyruvate kinaseLeishmania mexicana mexicanaPotency17.78280.398113.744731.6228AID1721; AID1722
caspase-3Homo sapiens (human)Potency1.80580.013326.981070.7614AID1346978
IDH1Homo sapiens (human)Potency14.58100.005210.865235.4813AID686970
aryl hydrocarbon receptorHomo sapiens (human)Potency7.60970.000723.06741,258.9301AID743085; AID743122
cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_aHomo sapiens (human)Potency2.74540.001723.839378.1014AID743083
activating transcription factor 6Homo sapiens (human)Potency54.94100.143427.612159.8106AID1159516; AID1159519
nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105), isoform CRA_aHomo sapiens (human)Potency54.941019.739145.978464.9432AID1159509
v-jun sarcoma virus 17 oncogene homolog (avian)Homo sapiens (human)Potency54.94100.057821.109761.2679AID1159526; AID1159528
nuclear receptor subfamily 1, group I, member 2Rattus norvegicus (Norway rat)Potency3.98110.10009.191631.6228AID1346983
Bloom syndrome protein isoform 1Homo sapiens (human)Potency28.18380.540617.639296.1227AID2364; AID2528
NPC intracellular cholesterol transporter 1 precursorHomo sapiens (human)Potency1.19900.01262.451825.0177AID485313
peripheral myelin protein 22 isoform 1Homo sapiens (human)Potency37.933023.934123.934123.9341AID1967
cellular tumor antigen p53 isoform aHomo sapiens (human)Potency10.00000.316212.443531.6228AID902; AID924
cytochrome P450 2C19 precursorHomo sapiens (human)Potency15.84890.00255.840031.6228AID899
cytochrome P450 2C9 precursorHomo sapiens (human)Potency31.62280.00636.904339.8107AID883
thyroid hormone receptor beta isoform aHomo sapiens (human)Potency44.66840.010039.53711,122.0200AID1479
nuclear factor erythroid 2-related factor 2 isoform 2Homo sapiens (human)Potency2.05960.00419.984825.9290AID504444
thyroid hormone receptor beta isoform 2Rattus norvegicus (Norway rat)Potency4.42250.000323.4451159.6830AID743065; AID743067
histone deacetylase 9 isoform 3Homo sapiens (human)Potency1.75610.037617.082361.1927AID1259364; AID1259388
heat shock protein beta-1Homo sapiens (human)Potency29.19450.042027.378961.6448AID743210; AID743228
huntingtin isoform 2Homo sapiens (human)Potency2.96980.000618.41981,122.0200AID2669; AID2673
ras-related protein Rab-9AHomo sapiens (human)Potency1.07160.00022.621531.4954AID485297
nuclear factor erythroid 2-related factor 2 isoform 1Homo sapiens (human)Potency23.16860.000627.21521,122.0200AID743202; AID743219
DNA polymerase iota isoform a (long)Homo sapiens (human)Potency25.11890.050127.073689.1251AID588590
urokinase-type plasminogen activator precursorMus musculus (house mouse)Potency8.91250.15855.287912.5893AID540303
plasminogen precursorMus musculus (house mouse)Potency8.91250.15855.287912.5893AID540303
urokinase plasminogen activator surface receptor precursorMus musculus (house mouse)Potency8.91250.15855.287912.5893AID540303
nuclear receptor ROR-gamma isoform 1Mus musculus (house mouse)Potency35.48130.00798.23321,122.0200AID2551
gemininHomo sapiens (human)Potency1.87140.004611.374133.4983AID463097; AID624297
peripheral myelin protein 22Rattus norvegicus (Norway rat)Potency1.38390.005612.367736.1254AID624032; AID624044
survival motor neuron protein isoform dHomo sapiens (human)Potency12.87950.125912.234435.4813AID1458; AID1740
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency2.82140.031610.279239.8107AID884; AID885
histone acetyltransferase KAT2A isoform 1Homo sapiens (human)Potency39.81070.251215.843239.8107AID504327
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency17.01570.00106.000935.4813AID943; AID944
lamin isoform A-delta10Homo sapiens (human)Potency7.06430.891312.067628.1838AID1487
neuropeptide S receptor isoform AHomo sapiens (human)Potency0.07940.015812.3113615.5000AID1461
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Voltage-dependent calcium channel gamma-2 subunitMus musculus (house mouse)Potency7.04030.001557.789015,848.9004AID1259244
Interferon betaHomo sapiens (human)Potency18.09610.00339.158239.8107AID1347407; AID1347411; AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency13.80290.01238.964839.8107AID1645842
Integrin beta-3Homo sapiens (human)Potency10.00000.316211.415731.6228AID924
Integrin alpha-IIbHomo sapiens (human)Potency10.00000.316211.415731.6228AID924
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Glutamate receptor 2Rattus norvegicus (Norway rat)Potency7.04030.001551.739315,848.9004AID1259244
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Endothelin receptor type BRattus norvegicus (Norway rat)Potency17.78280.562315.160931.6228AID1721
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Endothelin-1 receptorRattus norvegicus (Norway rat)Potency17.78280.562315.160931.6228AID1721
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Histamine H2 receptorCavia porcellus (domestic guinea pig)Potency31.62280.00638.235039.8107AID883
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency13.80290.01238.964839.8107AID1645842
ATPase family AAA domain-containing protein 5Homo sapiens (human)Potency3.90220.011917.942071.5630AID651632; AID720516
Ataxin-2Homo sapiens (human)Potency3.90220.011912.222168.7989AID651632
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency2.82141.000012.224831.6228AID885
cytochrome P450 2C9, partialHomo sapiens (human)Potency13.80290.01238.964839.8107AID1645842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ATP-binding cassette sub-family C member 3Homo sapiens (human)IC50 (µMol)133.00000.63154.45319.3000AID1473740
Multidrug resistance-associated protein 4Homo sapiens (human)IC50 (µMol)133.00000.20005.677410.0000AID1473741
Dihydroorotate dehydrogenase (quinone), mitochondrialMus musculus (house mouse)IC50 (µMol)0.03000.03000.10300.1560AID55726
Bile salt export pumpRattus norvegicus (Norway rat)IC50 (µMol)111.60000.40002.75008.6000AID1209456
Bile salt export pumpHomo sapiens (human)IC50 (µMol)140.13330.11007.190310.0000AID1209455; AID1449628; AID1473738
Cytochrome P450 1A2Homo sapiens (human)IC50 (µMol)0.50000.00011.774010.0000AID625245
Aldo-keto reductase family 1 member B1Rattus norvegicus (Norway rat)IC50 (µMol)4.63000.00041.877310.0000AID625207
Aldo-keto reductase family 1 member B1Rattus norvegicus (Norway rat)Ki4.59100.00322.28879.3160AID625207
Amine oxidase [flavin-containing] AHomo sapiens (human)IC50 (µMol)20.69600.00002.37899.7700AID625150
Sodium-dependent noradrenaline transporter Homo sapiens (human)IC50 (µMol)4.63000.00081.541620.0000AID625207
Sodium-dependent noradrenaline transporter Homo sapiens (human)Ki4.59100.00031.465610.0000AID625207
Sodium-dependent dopamine transporter Homo sapiens (human)IC50 (µMol)2.88400.00071.841946.0000AID625256
Sodium-dependent dopamine transporter Homo sapiens (human)Ki2.29100.00021.11158.0280AID625256
Dihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)IC50 (µMol)7.93330.00050.742710.0000AID1754739; AID55739; AID55740
Dihydroorotate dehydrogenase (quinone), mitochondrialRattus norvegicus (Norway rat)IC50 (µMol)0.00900.00900.14100.7000AID55727
Canalicular multispecific organic anion transporter 1Homo sapiens (human)IC50 (µMol)133.00002.41006.343310.0000AID1473739
Protein-arginine deiminase type-4Homo sapiens (human)IC50 (µMol)2,400.00002.50004.20005.9000AID320706
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
matrix metalloproteinase 1, partialHomo sapiens (human)EC50 (µMol)5.65001.060010.759427.6000AID618
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (236)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
bile acid and bile salt transportATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transportATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
leukotriene transportATP-binding cassette sub-family C member 3Homo sapiens (human)
monoatomic anion transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transport across blood-brain barrierATP-binding cassette sub-family C member 3Homo sapiens (human)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
negative regulation of low-density lipoprotein receptor activityIntegrin beta-3Homo sapiens (human)
positive regulation of protein phosphorylationIntegrin beta-3Homo sapiens (human)
positive regulation of endothelial cell proliferationIntegrin beta-3Homo sapiens (human)
positive regulation of cell-matrix adhesionIntegrin beta-3Homo sapiens (human)
cell-substrate junction assemblyIntegrin beta-3Homo sapiens (human)
cell adhesionIntegrin beta-3Homo sapiens (human)
cell-matrix adhesionIntegrin beta-3Homo sapiens (human)
integrin-mediated signaling pathwayIntegrin beta-3Homo sapiens (human)
embryo implantationIntegrin beta-3Homo sapiens (human)
blood coagulationIntegrin beta-3Homo sapiens (human)
positive regulation of endothelial cell migrationIntegrin beta-3Homo sapiens (human)
positive regulation of gene expressionIntegrin beta-3Homo sapiens (human)
negative regulation of macrophage derived foam cell differentiationIntegrin beta-3Homo sapiens (human)
positive regulation of fibroblast migrationIntegrin beta-3Homo sapiens (human)
negative regulation of lipid storageIntegrin beta-3Homo sapiens (human)
response to activityIntegrin beta-3Homo sapiens (human)
smooth muscle cell migrationIntegrin beta-3Homo sapiens (human)
positive regulation of smooth muscle cell migrationIntegrin beta-3Homo sapiens (human)
platelet activationIntegrin beta-3Homo sapiens (human)
positive regulation of vascular endothelial growth factor receptor signaling pathwayIntegrin beta-3Homo sapiens (human)
cell-substrate adhesionIntegrin beta-3Homo sapiens (human)
activation of protein kinase activityIntegrin beta-3Homo sapiens (human)
negative regulation of lipid transportIntegrin beta-3Homo sapiens (human)
regulation of protein localizationIntegrin beta-3Homo sapiens (human)
regulation of actin cytoskeleton organizationIntegrin beta-3Homo sapiens (human)
cell adhesion mediated by integrinIntegrin beta-3Homo sapiens (human)
positive regulation of cell adhesion mediated by integrinIntegrin beta-3Homo sapiens (human)
positive regulation of osteoblast proliferationIntegrin beta-3Homo sapiens (human)
heterotypic cell-cell adhesionIntegrin beta-3Homo sapiens (human)
substrate adhesion-dependent cell spreadingIntegrin beta-3Homo sapiens (human)
tube developmentIntegrin beta-3Homo sapiens (human)
wound healing, spreading of epidermal cellsIntegrin beta-3Homo sapiens (human)
cellular response to platelet-derived growth factor stimulusIntegrin beta-3Homo sapiens (human)
apolipoprotein A-I-mediated signaling pathwayIntegrin beta-3Homo sapiens (human)
wound healingIntegrin beta-3Homo sapiens (human)
apoptotic cell clearanceIntegrin beta-3Homo sapiens (human)
regulation of bone resorptionIntegrin beta-3Homo sapiens (human)
positive regulation of angiogenesisIntegrin beta-3Homo sapiens (human)
positive regulation of bone resorptionIntegrin beta-3Homo sapiens (human)
symbiont entry into host cellIntegrin beta-3Homo sapiens (human)
platelet-derived growth factor receptor signaling pathwayIntegrin beta-3Homo sapiens (human)
positive regulation of fibroblast proliferationIntegrin beta-3Homo sapiens (human)
mesodermal cell differentiationIntegrin beta-3Homo sapiens (human)
positive regulation of smooth muscle cell proliferationIntegrin beta-3Homo sapiens (human)
positive regulation of peptidyl-tyrosine phosphorylationIntegrin beta-3Homo sapiens (human)
negative regulation of lipoprotein metabolic processIntegrin beta-3Homo sapiens (human)
negative chemotaxisIntegrin beta-3Homo sapiens (human)
regulation of release of sequestered calcium ion into cytosolIntegrin beta-3Homo sapiens (human)
regulation of serotonin uptakeIntegrin beta-3Homo sapiens (human)
angiogenesis involved in wound healingIntegrin beta-3Homo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeIntegrin beta-3Homo sapiens (human)
platelet aggregationIntegrin beta-3Homo sapiens (human)
cellular response to mechanical stimulusIntegrin beta-3Homo sapiens (human)
cellular response to xenobiotic stimulusIntegrin beta-3Homo sapiens (human)
positive regulation of glomerular mesangial cell proliferationIntegrin beta-3Homo sapiens (human)
blood coagulation, fibrin clot formationIntegrin beta-3Homo sapiens (human)
maintenance of postsynaptic specialization structureIntegrin beta-3Homo sapiens (human)
regulation of postsynaptic neurotransmitter receptor internalizationIntegrin beta-3Homo sapiens (human)
regulation of postsynaptic neurotransmitter receptor diffusion trappingIntegrin beta-3Homo sapiens (human)
positive regulation of substrate adhesion-dependent cell spreadingIntegrin beta-3Homo sapiens (human)
positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathwayIntegrin beta-3Homo sapiens (human)
regulation of trophoblast cell migrationIntegrin beta-3Homo sapiens (human)
regulation of extracellular matrix organizationIntegrin beta-3Homo sapiens (human)
cellular response to insulin-like growth factor stimulusIntegrin beta-3Homo sapiens (human)
negative regulation of endothelial cell apoptotic processIntegrin beta-3Homo sapiens (human)
positive regulation of T cell migrationIntegrin beta-3Homo sapiens (human)
cell migrationIntegrin beta-3Homo sapiens (human)
steroid catabolic processCytochrome P450 1A2Homo sapiens (human)
porphyrin-containing compound metabolic processCytochrome P450 1A2Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 1A2Homo sapiens (human)
cholesterol metabolic processCytochrome P450 1A2Homo sapiens (human)
estrogen metabolic processCytochrome P450 1A2Homo sapiens (human)
toxin biosynthetic processCytochrome P450 1A2Homo sapiens (human)
post-embryonic developmentCytochrome P450 1A2Homo sapiens (human)
alkaloid metabolic processCytochrome P450 1A2Homo sapiens (human)
regulation of gene expressionCytochrome P450 1A2Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 1A2Homo sapiens (human)
dibenzo-p-dioxin metabolic processCytochrome P450 1A2Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 1A2Homo sapiens (human)
lung developmentCytochrome P450 1A2Homo sapiens (human)
methylationCytochrome P450 1A2Homo sapiens (human)
monocarboxylic acid metabolic processCytochrome P450 1A2Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 1A2Homo sapiens (human)
retinol metabolic processCytochrome P450 1A2Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 1A2Homo sapiens (human)
cellular respirationCytochrome P450 1A2Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 1A2Homo sapiens (human)
hydrogen peroxide biosynthetic processCytochrome P450 1A2Homo sapiens (human)
oxidative demethylationCytochrome P450 1A2Homo sapiens (human)
cellular response to cadmium ionCytochrome P450 1A2Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 1A2Homo sapiens (human)
positive regulation of leukocyte migrationIntegrin alpha-IIbHomo sapiens (human)
cell-matrix adhesionIntegrin alpha-IIbHomo sapiens (human)
integrin-mediated signaling pathwayIntegrin alpha-IIbHomo sapiens (human)
angiogenesisIntegrin alpha-IIbHomo sapiens (human)
cell-cell adhesionIntegrin alpha-IIbHomo sapiens (human)
cell adhesion mediated by integrinIntegrin alpha-IIbHomo sapiens (human)
biogenic amine metabolic processAmine oxidase [flavin-containing] AHomo sapiens (human)
positive regulation of signal transductionAmine oxidase [flavin-containing] AHomo sapiens (human)
dopamine catabolic processAmine oxidase [flavin-containing] AHomo sapiens (human)
monoamine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent noradrenaline transporter Homo sapiens (human)
chemical synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent noradrenaline transporter Homo sapiens (human)
response to painSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent noradrenaline transporter Homo sapiens (human)
neuron cellular homeostasisSodium-dependent noradrenaline transporter Homo sapiens (human)
amino acid transportSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transportSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent dopamine transporter Homo sapiens (human)
lactationSodium-dependent dopamine transporter Homo sapiens (human)
sensory perception of smellSodium-dependent dopamine transporter Homo sapiens (human)
locomotory behaviorSodium-dependent dopamine transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent dopamine transporter Homo sapiens (human)
response to iron ionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine transportSodium-dependent dopamine transporter Homo sapiens (human)
adenohypophysis developmentSodium-dependent dopamine transporter Homo sapiens (human)
response to nicotineSodium-dependent dopamine transporter Homo sapiens (human)
positive regulation of multicellular organism growthSodium-dependent dopamine transporter Homo sapiens (human)
regulation of dopamine metabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to cocaineSodium-dependent dopamine transporter Homo sapiens (human)
dopamine biosynthetic processSodium-dependent dopamine transporter Homo sapiens (human)
dopamine catabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to ethanolSodium-dependent dopamine transporter Homo sapiens (human)
cognitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent dopamine transporter Homo sapiens (human)
response to cAMPSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
prepulse inhibitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
hyaloid vascular plexus regressionSodium-dependent dopamine transporter Homo sapiens (human)
amino acid transportSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine transportSodium-dependent dopamine transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent dopamine transporter Homo sapiens (human)
UDP biosynthetic processDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
'de novo' UMP biosynthetic processDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
pyrimidine ribonucleotide biosynthetic processDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
'de novo' pyrimidine nucleobase biosynthetic processDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
xenobiotic metabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
negative regulation of gene expressionCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bile acid and bile salt transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
heme catabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic export from cellCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transepithelial transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
leukotriene transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
monoatomic anion transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell population proliferationATPase family AAA domain-containing protein 5Homo sapiens (human)
positive regulation of B cell proliferationATPase family AAA domain-containing protein 5Homo sapiens (human)
nuclear DNA replicationATPase family AAA domain-containing protein 5Homo sapiens (human)
signal transduction in response to DNA damageATPase family AAA domain-containing protein 5Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorATPase family AAA domain-containing protein 5Homo sapiens (human)
isotype switchingATPase family AAA domain-containing protein 5Homo sapiens (human)
positive regulation of DNA replicationATPase family AAA domain-containing protein 5Homo sapiens (human)
positive regulation of isotype switching to IgG isotypesATPase family AAA domain-containing protein 5Homo sapiens (human)
DNA clamp unloadingATPase family AAA domain-containing protein 5Homo sapiens (human)
regulation of mitotic cell cycle phase transitionATPase family AAA domain-containing protein 5Homo sapiens (human)
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorATPase family AAA domain-containing protein 5Homo sapiens (human)
positive regulation of cell cycle G2/M phase transitionATPase family AAA domain-containing protein 5Homo sapiens (human)
negative regulation of receptor internalizationAtaxin-2Homo sapiens (human)
regulation of translationAtaxin-2Homo sapiens (human)
RNA metabolic processAtaxin-2Homo sapiens (human)
P-body assemblyAtaxin-2Homo sapiens (human)
stress granule assemblyAtaxin-2Homo sapiens (human)
RNA transportAtaxin-2Homo sapiens (human)
chromatin organizationProtein-arginine deiminase type-4Homo sapiens (human)
nucleosome assemblyProtein-arginine deiminase type-4Homo sapiens (human)
chromatin remodelingProtein-arginine deiminase type-4Homo sapiens (human)
stem cell population maintenanceProtein-arginine deiminase type-4Homo sapiens (human)
protein modification processProtein-arginine deiminase type-4Homo sapiens (human)
post-translational protein modificationProtein-arginine deiminase type-4Homo sapiens (human)
innate immune responseProtein-arginine deiminase type-4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (104)

Processvia Protein(s)Taxonomy
ATP bindingATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type bile acid transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATP hydrolysis activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
icosanoid transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
fibroblast growth factor bindingIntegrin beta-3Homo sapiens (human)
C-X3-C chemokine bindingIntegrin beta-3Homo sapiens (human)
insulin-like growth factor I bindingIntegrin beta-3Homo sapiens (human)
neuregulin bindingIntegrin beta-3Homo sapiens (human)
virus receptor activityIntegrin beta-3Homo sapiens (human)
fibronectin bindingIntegrin beta-3Homo sapiens (human)
protease bindingIntegrin beta-3Homo sapiens (human)
protein disulfide isomerase activityIntegrin beta-3Homo sapiens (human)
protein kinase C bindingIntegrin beta-3Homo sapiens (human)
platelet-derived growth factor receptor bindingIntegrin beta-3Homo sapiens (human)
integrin bindingIntegrin beta-3Homo sapiens (human)
protein bindingIntegrin beta-3Homo sapiens (human)
coreceptor activityIntegrin beta-3Homo sapiens (human)
enzyme bindingIntegrin beta-3Homo sapiens (human)
identical protein bindingIntegrin beta-3Homo sapiens (human)
vascular endothelial growth factor receptor 2 bindingIntegrin beta-3Homo sapiens (human)
metal ion bindingIntegrin beta-3Homo sapiens (human)
cell adhesion molecule bindingIntegrin beta-3Homo sapiens (human)
extracellular matrix bindingIntegrin beta-3Homo sapiens (human)
fibrinogen bindingIntegrin beta-3Homo sapiens (human)
monooxygenase activityCytochrome P450 1A2Homo sapiens (human)
iron ion bindingCytochrome P450 1A2Homo sapiens (human)
protein bindingCytochrome P450 1A2Homo sapiens (human)
electron transfer activityCytochrome P450 1A2Homo sapiens (human)
oxidoreductase activityCytochrome P450 1A2Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 1A2Homo sapiens (human)
enzyme bindingCytochrome P450 1A2Homo sapiens (human)
heme bindingCytochrome P450 1A2Homo sapiens (human)
demethylase activityCytochrome P450 1A2Homo sapiens (human)
caffeine oxidase activityCytochrome P450 1A2Homo sapiens (human)
aromatase activityCytochrome P450 1A2Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 1A2Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 1A2Homo sapiens (human)
hydroperoxy icosatetraenoate dehydratase activityCytochrome P450 1A2Homo sapiens (human)
protein bindingIntegrin alpha-IIbHomo sapiens (human)
identical protein bindingIntegrin alpha-IIbHomo sapiens (human)
metal ion bindingIntegrin alpha-IIbHomo sapiens (human)
extracellular matrix bindingIntegrin alpha-IIbHomo sapiens (human)
molecular adaptor activityIntegrin alpha-IIbHomo sapiens (human)
fibrinogen bindingIntegrin alpha-IIbHomo sapiens (human)
integrin bindingIntegrin alpha-IIbHomo sapiens (human)
protein bindingAmine oxidase [flavin-containing] AHomo sapiens (human)
primary amine oxidase activityAmine oxidase [flavin-containing] AHomo sapiens (human)
aliphatic amine oxidase activityAmine oxidase [flavin-containing] AHomo sapiens (human)
monoamine oxidase activityAmine oxidase [flavin-containing] AHomo sapiens (human)
flavin adenine dinucleotide bindingAmine oxidase [flavin-containing] AHomo sapiens (human)
actin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
protein bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
alpha-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
metal ion bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
beta-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
protease bindingSodium-dependent dopamine transporter Homo sapiens (human)
signaling receptor bindingSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
protein bindingSodium-dependent dopamine transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine bindingSodium-dependent dopamine transporter Homo sapiens (human)
amine bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein-containing complex bindingSodium-dependent dopamine transporter Homo sapiens (human)
metal ion bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein phosphatase 2A bindingSodium-dependent dopamine transporter Homo sapiens (human)
heterocyclic compound bindingSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dihydroorotase activityDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
protein bindingDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
dihydroorotate dehydrogenase (quinone) activityDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
dihydroorotate dehydrogenase activityDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
organic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type xenobiotic transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP hydrolysis activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
protein bindingATPase family AAA domain-containing protein 5Homo sapiens (human)
ATP bindingATPase family AAA domain-containing protein 5Homo sapiens (human)
ATP hydrolysis activityATPase family AAA domain-containing protein 5Homo sapiens (human)
DNA clamp unloader activityATPase family AAA domain-containing protein 5Homo sapiens (human)
DNA bindingATPase family AAA domain-containing protein 5Homo sapiens (human)
RNA bindingAtaxin-2Homo sapiens (human)
epidermal growth factor receptor bindingAtaxin-2Homo sapiens (human)
protein bindingAtaxin-2Homo sapiens (human)
mRNA bindingAtaxin-2Homo sapiens (human)
protein-arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
calcium ion bindingProtein-arginine deiminase type-4Homo sapiens (human)
protein bindingProtein-arginine deiminase type-4Homo sapiens (human)
identical protein bindingProtein-arginine deiminase type-4Homo sapiens (human)
histone arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
histone H3R2 arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
histone H3R8 arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
histone H3R17 arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
histone H3R26 arginine deiminase activityProtein-arginine deiminase type-4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (74)

Processvia Protein(s)Taxonomy
plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basal plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basolateral plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
glutamatergic synapseIntegrin beta-3Homo sapiens (human)
nucleusIntegrin beta-3Homo sapiens (human)
nucleoplasmIntegrin beta-3Homo sapiens (human)
plasma membraneIntegrin beta-3Homo sapiens (human)
cell-cell junctionIntegrin beta-3Homo sapiens (human)
focal adhesionIntegrin beta-3Homo sapiens (human)
external side of plasma membraneIntegrin beta-3Homo sapiens (human)
cell surfaceIntegrin beta-3Homo sapiens (human)
apical plasma membraneIntegrin beta-3Homo sapiens (human)
platelet alpha granule membraneIntegrin beta-3Homo sapiens (human)
lamellipodium membraneIntegrin beta-3Homo sapiens (human)
filopodium membraneIntegrin beta-3Homo sapiens (human)
microvillus membraneIntegrin beta-3Homo sapiens (human)
ruffle membraneIntegrin beta-3Homo sapiens (human)
integrin alphav-beta3 complexIntegrin beta-3Homo sapiens (human)
melanosomeIntegrin beta-3Homo sapiens (human)
synapseIntegrin beta-3Homo sapiens (human)
postsynaptic membraneIntegrin beta-3Homo sapiens (human)
extracellular exosomeIntegrin beta-3Homo sapiens (human)
integrin alphaIIb-beta3 complexIntegrin beta-3Homo sapiens (human)
glycinergic synapseIntegrin beta-3Homo sapiens (human)
integrin complexIntegrin beta-3Homo sapiens (human)
protein-containing complexIntegrin beta-3Homo sapiens (human)
alphav-beta3 integrin-PKCalpha complexIntegrin beta-3Homo sapiens (human)
alphav-beta3 integrin-IGF-1-IGF1R complexIntegrin beta-3Homo sapiens (human)
alphav-beta3 integrin-HMGB1 complexIntegrin beta-3Homo sapiens (human)
receptor complexIntegrin beta-3Homo sapiens (human)
alphav-beta3 integrin-vitronectin complexIntegrin beta-3Homo sapiens (human)
alpha9-beta1 integrin-ADAM8 complexIntegrin beta-3Homo sapiens (human)
focal adhesionIntegrin beta-3Homo sapiens (human)
cell surfaceIntegrin beta-3Homo sapiens (human)
synapseIntegrin beta-3Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 1A2Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1A2Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1A2Homo sapiens (human)
plasma membraneIntegrin alpha-IIbHomo sapiens (human)
focal adhesionIntegrin alpha-IIbHomo sapiens (human)
cell surfaceIntegrin alpha-IIbHomo sapiens (human)
platelet alpha granule membraneIntegrin alpha-IIbHomo sapiens (human)
extracellular exosomeIntegrin alpha-IIbHomo sapiens (human)
integrin alphaIIb-beta3 complexIntegrin alpha-IIbHomo sapiens (human)
blood microparticleIntegrin alpha-IIbHomo sapiens (human)
integrin complexIntegrin alpha-IIbHomo sapiens (human)
external side of plasma membraneIntegrin alpha-IIbHomo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor 2Rattus norvegicus (Norway rat)
mitochondrionAmine oxidase [flavin-containing] AHomo sapiens (human)
mitochondrial outer membraneAmine oxidase [flavin-containing] AHomo sapiens (human)
cytosolAmine oxidase [flavin-containing] AHomo sapiens (human)
mitochondrionAmine oxidase [flavin-containing] AHomo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
cell surfaceSodium-dependent noradrenaline transporter Homo sapiens (human)
membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
presynaptic membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
axonSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
cytoplasmSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
cell surfaceSodium-dependent dopamine transporter Homo sapiens (human)
membraneSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
neuron projectionSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell bodySodium-dependent dopamine transporter Homo sapiens (human)
axon terminusSodium-dependent dopamine transporter Homo sapiens (human)
membrane raftSodium-dependent dopamine transporter Homo sapiens (human)
postsynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
dopaminergic synapseSodium-dependent dopamine transporter Homo sapiens (human)
flotillin complexSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
presynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent dopamine transporter Homo sapiens (human)
nucleoplasmDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
mitochondrionDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
mitochondrial inner membraneDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
cytosolDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
mitochondrial inner membraneDihydroorotate dehydrogenase (quinone), mitochondrialHomo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell surfaceCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
intercellular canaliculusCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
Elg1 RFC-like complexATPase family AAA domain-containing protein 5Homo sapiens (human)
nucleusATPase family AAA domain-containing protein 5Homo sapiens (human)
cytoplasmAtaxin-2Homo sapiens (human)
Golgi apparatusAtaxin-2Homo sapiens (human)
trans-Golgi networkAtaxin-2Homo sapiens (human)
cytosolAtaxin-2Homo sapiens (human)
cytoplasmic stress granuleAtaxin-2Homo sapiens (human)
membraneAtaxin-2Homo sapiens (human)
perinuclear region of cytoplasmAtaxin-2Homo sapiens (human)
ribonucleoprotein complexAtaxin-2Homo sapiens (human)
cytoplasmic stress granuleAtaxin-2Homo sapiens (human)
nucleusProtein-arginine deiminase type-4Homo sapiens (human)
nucleoplasmProtein-arginine deiminase type-4Homo sapiens (human)
cytosolProtein-arginine deiminase type-4Homo sapiens (human)
protein-containing complexProtein-arginine deiminase type-4Homo sapiens (human)
nucleusProtein-arginine deiminase type-4Homo sapiens (human)
cytoplasmProtein-arginine deiminase type-4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (216)

Assay IDTitleYearJournalArticle
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347113qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347112qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347116qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347118qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347111qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347115qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347127qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347123qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347119qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347126qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347109qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347125qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347121qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347110qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347114qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347122qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347129qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347124qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347128qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347117qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID567056Chemical stability of the compound in acidic medium at pH 1 after 6 hrs by RP-HPLC analysis2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588209Literature-mined public compounds from Greene et al multi-species hepatotoxicity modelling dataset2010Chemical research in toxicology, Jul-19, Volume: 23, Issue:7
Developing structure-activity relationships for the prediction of hepatotoxicity.
AID117376In vivo inhibition of TNP-specific immunoglobulin M production at 3 mg/kg/day, sc2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID1718009Antiproliferative activity against human M21 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID55727Inhibitory concentration tested against enzyme dihydroorotate dehydrogenase in rat1996Journal of medicinal chemistry, Nov-08, Volume: 39, Issue:23
Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.
AID567054Chemical stability of the compound in phosphate buffer at pH 7.4 assessed as half life at 100 uM after 30 mins by RP-HPLC analysis2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID1718012Antiproliferative activity against human M21 cells assessed as cell growth inhibition measured after 48 hrs in presence of uridine by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID1718015Antiproliferative activity against human HT-1080 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID625276FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of most concern for DILI2011Drug discovery today, Aug, Volume: 16, Issue:15-16
FDA-approved drug labeling for the study of drug-induced liver injury.
AID90645Immunosuppressant activity using human mixed leukocyte response (HMLR).1998Bioorganic & medicinal chemistry letters, Oct-06, Volume: 8, Issue:19
Synthesis and immunosuppressant activity of pyrazole carboxamides.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1636440Drug activation in human Hep3B cells assessed as human CYP2D6-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID1653798Substrate activity at human mARC2 expressed in Escherichia coli assessed as turnover rates at 500 uM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by UV-Visible spectroscopy based NADH assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID138445In vivo for its ability to inhibit delayed type hypersensitivity in mouse following 30 mg/kg administration.1996Journal of medicinal chemistry, Nov-08, Volume: 39, Issue:23
Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.
AID155442In vitro inhibition of expression of lymphocyte activated CD25 antigens induced by monoclonal antibody1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
AID695192Inhibition of Dihydroorotate dehydrogenase2012ACS medicinal chemistry letters, Oct-11, Volume: 3, Issue:10
Novel use of leflunomide and malononitrilamides: patent highlight.
AID142318In vitro inhibitory activity against murine antibody response to T-cell independent B-cell antigen TNP-LPS (type I)1998Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18
Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1821379Anti-colitis activity against DSS-induced C57BL/6 mouse model of acute colitis assessed as reduction in disease activity index at 10 mg/kg, po administered once daily for 10 days
AID1209455Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID1754739Inhibition of human DHODH2021Bioorganic & medicinal chemistry letters, 08-15, Volume: 46Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors.
AID567055Chemical stability of the compound in phosphate buffer at pH 7.4 assessed as unchanged compound level at 100 uM after 24 hrs by RP-HPLC analysis2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID1653803Substrate activity at human mARC1 expressed in Escherichia coli assessed as turnover rates at 500 uM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by LC-MS analysis based assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID194434In vivo for its ability to inhibit delayed type hypersensitivity in mouse following 10 mg/kg administration.1996Journal of medicinal chemistry, Nov-08, Volume: 39, Issue:23
Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.
AID106877In vitro T-cell immunosuppressive activity in the mouse mixed lymphocyte reaction (MLR)2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID1821381Anti-colitis activity against DSS-induced C57BL/6 mouse model of acute colitis assessed as recovery of colon length shortening at 10 mg/kg, po administered once daily for 10 days by HE staining based histopathological analysis
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1653808Substrate activity at human mARC2 expressed in Escherichia coli assessed as turnover rates at 500 uM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by LC-MS analysis based assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID117369In vivo inhibition of TNP-specific immunoglobulin G production at 3 mg/kg/day subcutaneous administration.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID155443In vitro inhibition of expression of lymphocyte activated CD71 antigens induced by monoclonal antibody1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
AID1604305Inhibition of Babesia bovis DHODH2019European journal of medicinal chemistry, Dec-01, Volume: 183Dihydroorotate dehydrogenase inhibitors in anti-infective drug research.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID695194Antiarthritic activity in rat with several spinal cord injury assessed as increase in locomotory function at 20 mg/kg/day for 7 days2012ACS medicinal chemistry letters, Oct-11, Volume: 3, Issue:10
Novel use of leflunomide and malononitrilamides: patent highlight.
AID132677In vitro inhibitory activity against mouse mixed lymphocyte reaction (MLR)1998Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18
Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.
AID468443Inhibition of human FAAH at 1 uM2009Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23
Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID210154In vitro inhibition of Ab formation from trinitrophenyl-lipopolysaccharide (TNP-LPS) B-cells.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID1473741Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1473740Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID521220Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay2007Nature chemical biology, May, Volume: 3, Issue:5
Chemical genetics reveals a complex functional ground state of neural stem cells.
AID1653793Substrate activity at human mARC1 expressed in Escherichia coli assessed as turnover rates at 500 uM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by UV-Visible spectroscopy based NADH assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1718011Antiproliferative activity against human HT-29 cells assessed as cell growth inhibition measured after 48 hrs in presence of uridine by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID1876104Cytotoxicity against HSG cells2022Journal of medicinal chemistry, 01-27, Volume: 65, Issue:2
Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.
AID120767Survival period of mice in days after xenotransplantation and for a dose of 3 mg/kg (Histology = antibody-mediated rejection).2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID567057Chemical stability of the compound in basic medium assessed as half life at pH 10 after 6 hrs by RP-HPLC analysis2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID1667214Inhibition of human SET7 overexpressed in Escherichia coli BL21 (DE3) cells at 25 uM preincubated for 15 mins followed by addition of SAM as substrate and biotinylated Histone H3 (1-50) peptide measured after 30 mins by AlphaLISA assay relative to control2020Bioorganic & medicinal chemistry, 04-01, Volume: 28, Issue:7
Computational discovery and biological evaluation of novel inhibitors targeting histone-lysine N-methyltransferase SET7.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID55739Immunosuppressive activity expressed as ability to inhibit human recombinant dihydroorotate dehydrogenase (DHODH)1998Bioorganic & medicinal chemistry letters, Aug-18, Volume: 8, Issue:16
Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1718008Antiproliferative activity against human HT-29 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID117374In vivo inhibition of TNP-specific immunoglobulin M production at 10 mg/kg/day, po2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID179062Immunosuppressant activity in rat using mixed leukocyte response (MLR).1998Bioorganic & medicinal chemistry letters, Oct-06, Volume: 8, Issue:19
Synthesis and immunosuppressant activity of pyrazole carboxamides.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID567059Inhibition of DHODH in Wistar rat liver homogenates by DCIP reduction assay2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1876103Antiviral activity against CMV2022Journal of medicinal chemistry, 01-27, Volume: 65, Issue:2
Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID117368In vivo inhibition of TNP-specific immunoglobulin G production at 10 mg/kg/day oral administration.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID120770Survival period of mice in days after xenotransplantation and for a dose of 50 mg/kg (Histology = no antibody-mediated rejection).2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID52790Inhibition of chymotrypsin at 250 uM2003Journal of medicinal chemistry, Oct-09, Volume: 46, Issue:21
Identification and prediction of promiscuous aggregating inhibitors among known drugs.
AID117379In vivo inhibition of TNP-specific immunoglobulin M production at 50 mg/kg/day, sc2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID55726Inhibitory concentration tested on enzyme dihydroorotate dehydrogenase in mouse1996Journal of medicinal chemistry, Nov-08, Volume: 39, Issue:23
Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.
AID155441In vitro inhibition of expression of lymphocyte activated CD2 antigens induced by monoclonal antibody1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
AID135187Inhibition of paw edema formation in mouse after an peroral dose of 10 mg/kg; Thickness of paw =2.45+/-0.14 mm1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
AID588210Human drug-induced liver injury (DILI) modelling dataset from Ekins et al2010Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 38, Issue:12
A predictive ligand-based Bayesian model for human drug-induced liver injury.
AID695193Immunosuppressive activity against autoimmune lymphocytes assessed as inhibition of cell expansion2012ACS medicinal chemistry letters, Oct-11, Volume: 3, Issue:10
Novel use of leflunomide and malononitrilamides: patent highlight.
AID320706Inhibition of PAD4 by ABPP-based assay2008Bioorganic & medicinal chemistry, Jan-15, Volume: 16, Issue:2
Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.
AID43581Inhibition of beta-lactamase at 100 uM2003Journal of medicinal chemistry, Oct-09, Volume: 46, Issue:21
Identification and prediction of promiscuous aggregating inhibitors among known drugs.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1636357Drug activation in human Hep3B cells assessed as human CYP3A4-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID117377In vivo inhibition of TNP-specific immunoglobulin M production at 30 mg/kg/day, sc2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID117371In vivo inhibition of TNP-specific immunoglobulin G production at 30 mg/kg/day subcutaneous administration.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID140308The compound was tested for in vitro mixed lymphocyte reaction.1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
AID94960In vitro inhibitory activity against Jurkat cell proliferation1998Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18
Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1473738Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1209457Unbound Cmax in human plasma2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID95447In vitro inhibition of Jurkat cell proliferation.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1209456Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID1718013Antiproliferative activity against human HT-1080 cells assessed as cell growth inhibition measured after 48 hrs in presence of uridine by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID567060Inhibition of DHODH in Wistar rat liver homogenates at 100 uM by DCIP reduction assay2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
1,2,5-Oxadiazole analogues of leflunomide and related compounds.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1718016Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID1473739Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID117372In vivo inhibition of TNP-specific immunoglobulin G production at 50 mg/kg/day subcutaneous administration.2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID120768Survival period of mice in days after xenotransplantation and for a dose of 30 mg/kg (Histology = antibody-mediated rejection, Chronic rejection).2001Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID695195Antiarthritic activity in rat with several spinal cord injury assessed as increase in voiding function at 20 mg/kg/day for 7 days2012ACS medicinal chemistry letters, Oct-11, Volume: 3, Issue:10
Novel use of leflunomide and malononitrilamides: patent highlight.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID55740In vitro inhibitory activity against human dihydroorotate dehydrogenase (DHODH)1998Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18
Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1718014Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition measured after 48 hrs in presence of uridine by SRB assay2020Bioorganic & medicinal chemistry, 11-15, Volume: 28, Issue:22
N-phenyl ureidobenzenesulfonates, a novel class of promising human dihydroorotate dehydrogenase inhibitors.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID106806Inhibition of malate dehydrogenase (MDH) at 400 uM2003Journal of medicinal chemistry, Oct-09, Volume: 46, Issue:21
Identification and prediction of promiscuous aggregating inhibitors among known drugs.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID132509Compound was tested in vitro for immunosuppressive activity which was measured in the mouse mixed lymphocyte reaction1998Bioorganic & medicinal chemistry letters, Aug-18, Volume: 8, Issue:16
Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.
AID1821380Anti-colitis activity against DSS-induced C57BL/6 mouse model of acute colitis assessed as recovery of body weight loss at 10 mg/kg, po administered once daily for 10 days
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID686947qHTS for small molecule inhibitors of Yes1 kinase: Primary Screen2013Bioorganic & medicinal chemistry letters, Aug-01, Volume: 23, Issue:15
Identification of potent Yes1 kinase inhibitors using a library screening approach.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
AID1347414qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: Secondary screen by immunofluorescence2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).2014Journal of biomolecular screening, Jul, Volume: 19, Issue:6
A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).
AID1346140Human dihydroorotate dehydrogenase (quinone) (Nucleoside synthesis and metabolism)1998Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18
Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.
AID1224864HCS microscopy assay (F508del-CFTR)2016PloS one, , Volume: 11, Issue:10
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,598)

TimeframeStudies, This Drug (%)All Drugs %
pre-19907 (0.44)18.7374
1990's223 (13.95)18.2507
2000's642 (40.18)29.6817
2010's549 (34.36)24.3611
2020's177 (11.08)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 107.01

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index107.01 (24.57)
Research Supply Index7.55 (2.92)
Research Growth Index6.52 (4.65)
Search Engine Demand Index195.11 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (107.01)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials173 (10.03%)5.53%
Reviews318 (18.43%)6.00%
Case Studies293 (16.99%)4.05%
Observational19 (1.10%)0.25%
Other922 (53.45%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (83)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase 2 Trial of Leflunomide, Pomalidomide, and Dexamethasone for Relapsed/Refractory Multiple Myeloma [NCT04508790]Phase 229 participants (Anticipated)Interventional2020-11-27Recruiting
The Cohort Study of East Chinese Takayasu's Arteritis (ECTA-cohort Study) [NCT03893136]1,000 participants (Anticipated)Observational2016-11-01Recruiting
IL-7 and IL-7R Expression in Peripheral Blood Mononuclear Cells, Peripheral Blood Monocytes or Differentiated Macrophages of Rheumatoid Arthritis Patients With Active vs. Inactive Disease Treated With DMARD and/or CIMZIA [NCT02451748]Phase 432 participants (Actual)Interventional2015-08-31Completed
Leflunomide Treatment for IgG4-RD [NCT03715699]70 participants (Anticipated)Interventional2018-07-01Recruiting
Comparison of Sulfasalazine Versus Leflunomide Based Combination Disease Modifying Anti-rheumatic Drug Therapy (DMARD) in Patients With Rheumatoid Arthritis Failing Methotrexate Monotherapy : A Randomized Control Trial [NCT02930343]Phase 3136 participants (Actual)Interventional2016-09-30Terminated(stopped due to Due to time constraints, the study was halted prematurely)
A Multicenter Randomized Placebo Controlled Treatment Study of Leflunomide in Polymyalgia Rheumatica [NCT03576794]Phase 394 participants (Anticipated)Interventional2019-03-01Recruiting
A Randomized Multicenter Trial Comparing Leflunomide and Azathioprine as Remission-Maintaining Treatment for Proliferative Lupus Glomerulonephritis. [NCT01172002]200 participants (Anticipated)Interventional2010-03-31Recruiting
Phase 2 Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma [NCT03952832]Phase 20 participants (Actual)Interventional2019-12-11Withdrawn(stopped due to Budget issues)
Effect of Sarilumab on Patient-reported Outcomes in Patients With Moderately to Severely Active Rheumatoid Arthritis and With Inadequate Response or Intolerance to Current Conventional Synthetic DMARDs or Tumor Necrosis Factor Inhibitors [NCT03449758]Phase 484 participants (Actual)Interventional2018-03-05Completed
A Prospective, Randomized, Controlled, Open Label, Assessor-blinded, Parallel-group Phase III Clinical Trial to Evaluate the Impact of Tapering Systemic Immunosuppressive Therapy in a Treat-to-target Approach on Maintaining Minimal Disease Activity in Adu [NCT04610476]Phase 3270 participants (Anticipated)Interventional2020-10-19Recruiting
A Relative Bioavailability, Parallel Study of Leflunomide 20 mg Tablets Under Non-Fasting Conditions [NCT00834405]Phase 137 participants (Actual)Interventional2002-04-30Completed
Clinical Effectiveness of Standard Step up Care (Methotrexate) Compared to Early Combination DMARD Therapy With Standard Step up Care Compared to Early Use of TNF Inhibitors With Standard Step up Care for the Treatment of Moderate to Severe Psoriatic Arth [NCT03739853]Phase 4315 participants (Anticipated)Interventional2019-05-14Recruiting
A Relative Bioavailability Study of 20 mg Leflunomide Tablets Under Fasting Conditions [NCT00834418]Phase 184 participants (Actual)Interventional2002-06-30Completed
A Randomized, Double-blind Double Dummy, Parallel Control and Multi-center Clinical Trial to Compare the Efficacy and Safety of Tacrolimus Capsules in Treatment of Lupus Nephritis With Leflunomide Tablets [NCT01342016]Phase 384 participants (Actual)Interventional2011-04-30Terminated(stopped due to Due to safety concern of active control drug)
Treatment Strategies for IgG4-RD Patients With Superficial Organ Involvement [NCT05789030]90 participants (Anticipated)Interventional2022-07-01Recruiting
Efficacy of Mycophenolate Mofetil Versus Leflunomide as Maintenance Treatment for IgG4-RD Patients With Internal Organ Involvement [NCT05789017]60 participants (Anticipated)Interventional2022-07-01Recruiting
Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response [NCT03414502]Phase 3400 participants (Anticipated)Interventional2007-12-10Recruiting
Leflunomide Associated With Topical Corticosteroids for Bullous Pemphigoid. An Open Prospective Study [NCT00802243]Phase 254 participants (Anticipated)Interventional2007-09-30Recruiting
A Phase II, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patient With Active Rhe [NCT01225393]Phase 2211 participants (Actual)Interventional2010-11-30Completed
Pilot Trial of Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies [NCT05443425]Phase 118 participants (Anticipated)Interventional2023-06-16Recruiting
Non Inferiority Trial for the Study of Acupuncture on Rheumatoid Arthritis [NCT01619176]10 participants (Actual)Interventional2012-10-31Completed
A Randomized, Double-blind, Multicenter Study Evaluating the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis [NCT02373202]Phase 391 participants (Actual)Interventional2015-02-28Completed
A Relative Bioavailability, Parallel Study Of Leflunomide 20 mg Tablets Under Fasting Conditions [NCT00946686]Phase 152 participants (Actual)Interventional2002-09-30Completed
To Compare the Relative Bioavailability of Leflunomide 20mg Tablets (Kali) With That of ARAVA 20mg Tablets(Aventis) Under Fasting Conditions [NCT00652665]Phase 152 participants (Actual)Interventional2003-06-30Completed
A Study of Safety and Efficacy of Leflunomide for Maintenance of Remission in IgG4 Related Disease [NCT02703194]Phase 468 participants (Actual)Interventional2016-03-31Completed
BK Viremia After Renal Transplantation: Screening, Early Diagnosis, Early Reduction in Immunosuppression and Treatment With Leflunomide (Arava) [NCT00684372]100 participants (Anticipated)Interventional2007-05-31Active, not recruiting
Pilot Trial of Leflunomide in Patients With CD30+ Lymphoproliferative Disorders [NCT04463615]Phase 21 participants (Actual)Interventional2021-05-05Completed
Comparison of Combination Disease Modifying Antirheumatic Drugs (DMARDs) With Single Drug (Methotrexate) Therapy in Early Rheumatoid Arthritis [NCT02644499]Phase 4186 participants (Actual)Interventional2015-12-31Completed
To Compare the Relative Bioavailability of Leflunomide 20mg Tablets (Kali) With That of ARAVA 20mg Tablets(Aventis) Under Fed Conditions [NCT00653003]Phase 162 participants (Actual)Interventional2003-12-31Completed
Phase 2 Trial of Leflunomide in African-American and European-American Patients With High-Risk Smoldering Multiple Myeloma [NCT05014646]Phase 220 participants (Anticipated)Interventional2022-03-07Recruiting
Comparison of the Efficacy and Safety of Leflunomide Versus Placebo Combine With the Basic Prednisone Therapy in Patients With Active Phase of Takayasu's Arteritis: a Randomized Controlled Double-blinded Trial [NCT02981979]116 participants (Anticipated)Interventional2016-12-31Recruiting
Triple III Comparison of Leflunomide Alone Versus Two DMARD Combinations (Leflunomide-Hydroxychloroquine-Sulfasalazine or Methotrexate-Hydroxychloroquine-Sulfasalazine) in the Treatment of Rheumatoid Arthritis [NCT00579878]Phase 369 participants (Actual)Interventional2001-03-27Completed
A Randomized, Open-Label Study in the Asia-Pacific Region Comparing the Safety and Efficacy of Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis [NCT00422227]Phase 4300 participants (Actual)Interventional2007-06-30Completed
The Clinical Study to Observe the Efficacy and Safety of Immunomodulators in Rheumatoid Arthritis Patients for 6 Months Treatment in China [NCT05626348]Phase 4400 participants (Anticipated)Interventional2021-12-22Recruiting
CHronic Nonbacterial Osteomyelitis International Registry (CHOIR) [NCT04725422]2,000 participants (Anticipated)Observational2018-08-01Recruiting
An Open, Randomized Study Treating Refractory Adult-onset Still's Disease With Interleukin-1 Receptor Antagonist Anakinra (Kineret), Compared to an Established, Single Anti-rheumatic Drug Treatment [NCT01033656]Phase 223 participants (Actual)Interventional2005-12-31Completed
The Research of Standard Diagnosis and Treatment for Henoch-Schonlein Purpura Nephritis in Children [NCT02532777]Phase 2100 participants (Anticipated)Interventional2015-08-31Recruiting
Pilot Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma [NCT04370483]Early Phase 11 participants (Actual)Interventional2020-10-08Active, not recruiting
Study of Therapeutic Effects and Side Effects of Leflunomide in Methotrexate Refractory Juvenile Idiopathic Arthritis [NCT02024334]Phase 430 participants (Anticipated)Interventional2013-06-30Recruiting
Leflunomide for Refractory Skin Henoch-Schonlein Purpura in Children [NCT05937880]36 participants (Anticipated)Interventional2023-01-01Recruiting
Leflunomide is Safe and Effective for the Induction and Maintenance of Idiopathic Pulmonary Hemosiderosis Remission [NCT05937191]Phase 1/Phase 234 participants (Anticipated)Interventional2023-06-01Recruiting
A Phase IA/IB Trial of Leflunomide in Patients With PTEN-null Advanced Solid Malignancies [NCT04997993]Phase 124 participants (Anticipated)Interventional2023-12-13Recruiting
An Open-Label, Multi-Center Study to Evaluation of Leflunomide Plus Methotexate for the Treatment of Rheumatoid Arthritis in DMARDs:(Disease-Modifying Antirheumatic Drug) na¿ve or Restart (Skip DMARDs More Than 4 Weeks) Subjects. [NCT00563849]Phase 474 participants (Actual)Interventional2003-05-31Completed
A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to at Least One Anti-TNF-α Therapy [NCT00476996]Phase 3836 participants (Actual)Interventional2007-05-15Terminated(stopped due to Recruitment was fully completed for this study; however, the study was terminated during conduct after the primary endpoint analysis was completed.)
A Safety and Feasibility Trial of Leflunomide in Patients With Steroid Dependent Chronic Graft-Versus-Host Disease [NCT04212416]Phase 124 participants (Anticipated)Interventional2020-05-12Recruiting
A 2 Year Prospective Multicentre Randomised Controlled Trial Comparing Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis. [NCT01172639]Phase 4400 participants (Actual)Interventional2009-02-28Completed
"Screening Protein Predictive of Response to Tumor Necrosis Factor-α Inhibitors Treatment in Chinese Rheumatoid Arthritis From Real World and Investigating Its Mechanism Through Signal Pathway" [NCT02878161]Phase 4240 participants (Anticipated)Interventional2016-01-31Enrolling by invitation
Assessment of the Early Efficacy Response Rate of Leflunomide According to the Initial Dosing Regimen in the Treatment of Naive-DMARD (Disease Modifying Anti-Rheumatic Drug) Early RA (Rheumatoid Arthritis)-Patients [NCT00596206]Phase 3124 participants (Actual)Interventional2007-12-31Completed
A Phase 1/2 Trial of Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy [NCT04532372]Phase 1/Phase 22 participants (Actual)Interventional2021-01-07Active, not recruiting
Assessment of Leflunomide Efficacy and Hepatotoxicity in Patients With Rheumatoid Arthritis Through Pharmacokinetic and Genetic Approaches [NCT04022525]80 participants (Actual)Observational2018-02-01Completed
A Randomized, Open Label, Phase II Multicenter Study of Non-Myeloablative Autologous Transplantation With Auto-CD34+HPC Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Systemic Lupus Erythematosus [NCT00230035]Phase 20 participants (Actual)Interventional2005-09-30Withdrawn(stopped due to Recommended by DSMB due to lack of accrual)
Phase 3 Study of Leflunomide Combined With Prednisone Treatment of Proliferative Lupus Nephritis as Induction Therapy [NCT00268567]Phase 2/Phase 30 participants Interventional2002-10-31Completed
Leflunomide for the Treatment of Ambulatory Patients With Mild COVID-19 [NCT04361214]Phase 120 participants (Anticipated)Interventional2020-05-05Recruiting
A Randomized, Double-Blind, Placebo Controlled Clinical Trial of Leflunomide in Systemic Lupus Erythematosus (SLE) [NCT00637819]Phase 227 participants (Actual)Interventional2003-01-31Completed
Objective Study in Rheumatoid Arthritis [NCT00451971]Phase 4249 participants (Actual)Interventional2002-03-31Completed
A Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Iguratimod or Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis [NCT02275299]Phase 4240 participants (Anticipated)Interventional2013-09-30Recruiting
A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists [NCT01709578]Phase 3546 participants (Actual)Interventional2012-10-31Completed
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of Leflunomide on HIV-1 Associated Immune Proliferation In Vivo [NCT00101374]Phase 141 participants (Actual)Interventional2005-01-05Completed
Randomized Controlled Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflu [NCT02714634]Phase 4286 participants (Anticipated)Interventional2016-03-30Recruiting
Efficacy of Leflunomide on Joint Inflammation and Destruction of Joint Integrity in Active Rheumatoid Arthritis (RA) Patients [NCT00280644]Phase 460 participants Interventional2004-04-30Completed
An Open-Label, Phase 2 Study to Treat Patients With Renal Allograft and Polyoma BK Viruria to Prevent Polyoma BK Viremia, Polyoma BK Nephropathy and Renal Allograft Rejection [NCT01620268]Phase 224 participants (Actual)Interventional2012-07-31Terminated(stopped due to Lack of recruitment)
Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis Patients With Active Disease Despite Methotrexate: an Ultrasound and Magnetic Resonance Imaging Study [NCT01659242]Phase 41 participants (Actual)Interventional2012-07-31Terminated
Efficacy and Safety of Xinfeng Capsule in the Treatment of Rheumatoid Arthritis (RA):A Randomized, Double-blind, Double-dummy, Multi-center Trial [NCT01774877]304 participants (Actual)Interventional2013-07-31Completed
A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists [NCT01768572]Phase 3202 participants (Actual)Interventional2013-03-31Completed
Pilot Study of Leflunomide for the Treatment of Uveitis [NCT00001863]Phase 216 participants Interventional1999-03-31Completed
A Phase I/II Dose-Escalation Trial of Leflunomide in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma [NCT02509052]Phase 1/Phase 212 participants (Actual)Interventional2015-12-02Completed
Clinical Effectiveness of Symptomatic Therapy Compared to Standard Step up Care for the Treatment of Low Impact Psoriatic Oligoarthritis: a 2 Arm Parallel Group Feasibility Study [NCT03797872]Phase 41 participants (Actual)Interventional2019-04-17Completed
Pilot Study of Leflunomide as First Line Therapy for Musculoskeletal GVHD [NCT04932564]Phase 210 participants (Anticipated)Interventional2021-06-15Recruiting
The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy [NCT01727193]Phase 3290 participants (Actual)Interventional2012-09-30Completed
Leflunomide in Combination With Vemurafenib in Patients With V600 Mutant Metastatic Melanoma [NCT01611675]Phase 13 participants (Actual)Interventional2012-07-31Terminated(stopped due to Adverse Events)
A 48-week, Multi-center, Randomized, Open-lable, Controlled Study to Assess the Response (ACR20) Using Different Disease-Modifying Antirheumatic Drugs Cycle Combination Regimen in Adult Patients With Active Rheumatoid Arthritis [NCT01617590]500 participants (Anticipated)Interventional2012-05-31Recruiting
A Phase II Open Label Study of SU101 for Patients With Anaplastic Astrocytoma in First Relapse [NCT00003775]Phase 260 participants (Actual)Interventional1998-12-31Completed
A Multicenter, Randomized, Open-Label, Parallel-Group Usability Study Of The Sarilumab Auto-Injector Device And A Prefilled Syringe In Patients With Moderate To Severe Active Rheumatoid Arthritis Who Are Candidates For Anti-IL6R Therapy [NCT02057250]Phase 3217 participants (Actual)Interventional2014-03-31Completed
Effectiveness of a Combination of Methotrexate and a Step Down Glucocorticoid Regimen (COBRA-Slim) for Remission Induction in Patients With Early Rheumatoid Arthritis (RA), With or Without Fast Access to 24 Weeks of Tumor Necrosis Factor (TNF) Blockade in [NCT03649061]Phase 4284 participants (Actual)Interventional2018-06-08Completed
A Randomized, Open-Label Phase II/III Study of SU101 Plus Mitoxantrone/Prednisone Compared to Mitoxantrone/Prednisone Alone in Patients With Hormone-Refractory Prostate Cancer [NCT00004071]Phase 2/Phase 30 participants Interventional1999-08-31Completed
NEw Clinical Endpoints in Patients With Primary Sjögren's Syndrome (pSS): an Interventional Trial Based on stratifYing Patients [NCT05113004]Phase 2300 participants (Anticipated)Interventional2022-01-20Recruiting
Targeting de Novo Pyrimidine Biosynthesis by Leflunomide as a Novel Concept for the Treatment of Corona Virus Disease 2019 (COVID-19) [NCT05007678]Phase 3178 participants (Actual)Interventional2020-09-16Completed
A Phase I/II Trial of Leflunomide in Women With Previously Treated Metastatic Triple Negative Cancers [NCT03709446]Phase 1/Phase 254 participants (Anticipated)Interventional2019-04-16Recruiting
A Randomized, Controlled Trial to Evaluate Leflunomide Plus Low Dose Corticosteroid Therapy in Progressive IgA Nephropathy With Renal Insufficiency [NCT04020328]Phase 470 participants (Anticipated)Interventional2019-09-12Recruiting
Multicenter, Open Label, Phase IIIb Study to Evaluate the Safety and Tolerability of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Methotrexate or Other Non-Biologic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Ar [NCT01941095]Phase 3100 participants (Actual)Interventional2013-11-20Completed
The Efficacy of Leflunomide for the Maintenance Therapy of ANCA Associated Vasculitis [NCT04737343]114 participants (Anticipated)Interventional2021-06-30Recruiting
A Phase III Randomized Study of SU101 Versus Procarbazine for Patients With Glioblastoma Multiforme in First Relapse [NCT00003293]Phase 30 participants Interventional1998-02-28Completed
Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial [NCT05605587]15 participants (Anticipated)Interventional2023-05-02Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00422227 (10) [back to overview]Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales
NCT00422227 (10) [back to overview]Percent Change From Baseline in Duration (Minutes) of Morning Stiffness
NCT00422227 (10) [back to overview]Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response
NCT00422227 (10) [back to overview]Percent Change From Baseline in DAS28 at Week 16
NCT00422227 (10) [back to overview]Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks
NCT00422227 (10) [back to overview]Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2
NCT00422227 (10) [back to overview]Percent Change From Baseline in Painful and Swollen Joint Counts
NCT00422227 (10) [back to overview]Percent Change From Baseline in Physician And Subject Global Assessments
NCT00422227 (10) [back to overview]Percentage of Participants Achieving ACR 20, 50, and 70 Responses
NCT00422227 (10) [back to overview]Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission)
NCT00476996 (8) [back to overview]Percentage of Participants With a Reduction in the HAQ-DI Score
NCT00476996 (8) [back to overview]Percentage of Participants With EULAR Response Rates of Good/ Moderate
NCT00476996 (8) [back to overview]Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses
NCT00476996 (8) [back to overview]Percentage of Participants With a Major Clinical Response
NCT00476996 (8) [back to overview]Change in DAS28 From Baseline
NCT00476996 (8) [back to overview]Percentage of Participants Achieving an ACR50 Response
NCT00476996 (8) [back to overview]Percentage of Participants Achieving an ACR70 Response
NCT00476996 (8) [back to overview]Percentage of Participants Achieving Disease Activity Score (DAS28) Remission
NCT00579878 (1) [back to overview]Measuring the Safety and Efficacy of a New DMARD, Leflunomide Alone or in Combination With Traditional DMARD's. Participants Reaching ACR 20 Response. at 48 Weeks
NCT00834405 (2) [back to overview]AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose (Per Participant) - Metabolite A77 1726
NCT00834405 (2) [back to overview]Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma
NCT00834418 (2) [back to overview]AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose - Metabolite A77 1726
NCT00834418 (2) [back to overview]Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma
NCT01172639 (7) [back to overview]Remission According to SDAI (Simple Disease Activity Index) at Week 16
NCT01172639 (7) [back to overview]Remission According to DAS28-CRP at Week 52
NCT01172639 (7) [back to overview]Remission According to DAS28-CRP at Week 16
NCT01172639 (7) [back to overview]Remission According to DAS28-CRP at Week 104
NCT01172639 (7) [back to overview]Clinically Significant Change in HAQ Score
NCT01172639 (7) [back to overview]Remission According to SDAI at Week 52
NCT01172639 (7) [back to overview]Remission According to SDAI at Week 104
NCT01619176 (9) [back to overview]DAS28 at 3 Weeks
NCT01619176 (9) [back to overview]DAS28 at 3 Months
NCT01619176 (9) [back to overview]ACR70 Response Rate at 3 Weeks
NCT01619176 (9) [back to overview]ACR70 Response Rate at 3 Months
NCT01619176 (9) [back to overview]ACR50 Response Rate at 3 Weeks
NCT01619176 (9) [back to overview]ACR50 Response Rate at 3 Months
NCT01619176 (9) [back to overview]ACR20 Response Rate at 3 Weeks
NCT01619176 (9) [back to overview]DAS28 at Baseline
NCT01619176 (9) [back to overview]ACR20 Response Rate at 3 Months
NCT01709578 (41) [back to overview]Change From Baseline in EQ-5D-3L VAS Scores at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
NCT01709578 (41) [back to overview]Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24
NCT01709578 (41) [back to overview]Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24
NCT01709578 (41) [back to overview]Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24
NCT01709578 (41) [back to overview]Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
NCT01709578 (41) [back to overview]Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24
NCT01709578 (41) [back to overview]Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in DAS28-CRP at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24
NCT01709578 (41) [back to overview]Percentage of Participants Achieving ACR70 Criteria at Week 24
NCT01709578 (41) [back to overview]Percentage of Participants Achieving ACR50 Criteria at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity
NCT01709578 (41) [back to overview]Change From Baseline in SF-36 MCS at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA
NCT01709578 (41) [back to overview]Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in RAID Scores at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in the FACIT-fatigue at Week 12
NCT01709578 (41) [back to overview]Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in Morning Stiffness VAS at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in HAQ-DI at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24
NCT01709578 (41) [back to overview]Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24
NCT01709578 (41) [back to overview]Change From Baseline in SF-36 at Week 12
NCT01709578 (41) [back to overview]Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12
NCT01768572 (1) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs)
NCT01941095 (19) [back to overview]Tocilizumab Serum Levels
NCT01941095 (19) [back to overview]Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24
NCT01941095 (19) [back to overview]Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation
NCT01941095 (19) [back to overview]Change From Baseline in DAS28-ESR up to Week 52
NCT01941095 (19) [back to overview]Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52
NCT01941095 (19) [back to overview]Change From Baseline in SJC28 up to Week 52
NCT01941095 (19) [back to overview]Change From Baseline in TJC28 up to Week 52
NCT01941095 (19) [back to overview]Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
NCT01941095 (19) [back to overview]HAQ-DI Score
NCT01941095 (19) [back to overview]Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation
NCT01941095 (19) [back to overview]Number of Participants With American College of Rheumatology 20 (ACR20) Response
NCT01941095 (19) [back to overview]Number of Participants With Anti-Tocilizumab Antibodies (ATA)
NCT01941095 (19) [back to overview]Patient Assessment of Pain, Using VAS Score
NCT01941095 (19) [back to overview]Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24
NCT01941095 (19) [back to overview]Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24
NCT01941095 (19) [back to overview]Percentage of Participants Who Received All Planned Study Medication (Compliance)
NCT01941095 (19) [back to overview]Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria
NCT01941095 (19) [back to overview]PGA, Using VAS Score
NCT01941095 (19) [back to overview]Soluble Interleukin-6 Receptor (sIL-6R) Levels
NCT02057250 (2) [back to overview]Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab
NCT02057250 (2) [back to overview]Number of Validated AID Associated Product Technical Failures (PTFs)
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
NCT02373202 (11) [back to overview]Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52
NCT02373202 (11) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT02373202 (11) [back to overview]Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
NCT02373202 (11) [back to overview]Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP)
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters
NCT02373202 (11) [back to overview]Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
NCT02509052 (5) [back to overview]Response Duration
NCT02509052 (5) [back to overview]MTD, Defined as the Highest Dose in Which =< 1/6 Patients Experience a Dose-limiting Toxicity, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
NCT02509052 (5) [back to overview]Clinical Benefit Response Rate (sCR/CR/VGPR/Partial Response [PR]/Minimal Response [MR] or Stable Disease [SD]), Assessed by IMWG Criteria
NCT02509052 (5) [back to overview]Best Overall Response Rate: Proportion of Patients Reaching CR by IMWG Criteria
NCT02509052 (5) [back to overview]Response Duration
NCT02930343 (4) [back to overview]Indian Health Assessment Questionnaire (iHAQ)
NCT02930343 (4) [back to overview]Number of Participants With Adverse Drug Reactions
NCT02930343 (4) [back to overview]Disease Activity as Per Ultrasound-7 (US-7) Score
NCT02930343 (4) [back to overview]Number of Patients Achieving Good EULAR Response at the End of 12 Weeks
NCT03449758 (30) [back to overview]Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24
NCT03449758 (30) [back to overview]Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Number of Participants Achieving Clinical Disease Activity Index: Low Disease Activity (CDAI Score <=10.0) and Remission (CDAI Score <=2.8) Weeks 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Number of Tender Joints at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12
NCT03449758 (30) [back to overview]Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24
NCT03449758 (30) [back to overview]Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Number of Swollen Joints at Baseline, Weeks 4, 12, and 24
NCT03449758 (30) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT03449758 (30) [back to overview]Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24
NCT03797872 (1) [back to overview]Number of Participants Who Are Eligible, Consent, and Complete the 48 Weeks Study
NCT04463615 (2) [back to overview]Overall Response Rate
NCT04463615 (2) [back to overview]Complete Response Rate

Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales

"VAS, participant indicates by marking a vertical line at an appropriate position through a horizontal line. The length of the line measures from left (in mm) and the value (in mm) is recorded. General Health VAS, in general how would you rate your heath over the last 2-3 weeks, 0mm equals very well and 100mm equals extremely bad. Pain VAS: indicate the amount of pain experienced during the last 2-3 days, 0 mm equals no pain and 100 mm equals pain as bad as it can be. Fatigue VAS: how fatigued or tired have you been over the last week, range =No Fatigue - Extremely Fatigued." (NCT00422227)
Timeframe: Week 2, 4, 8, 12, 16

,
InterventionPercent change (Number)
General Health - Week 2General Health - Week 4General Health - Week 8General Health - Week 12General Health - Week 16Pain - Week 2Pain - Week 4Pain - Week 8Pain - Week 12Pain - Week 16Fatigue - Week 2Fatigue - Week 4Fatigue - Week 8Fatigue - Week 12Fatigue - Week 16
DMARD/MTX8.8822.7827.8630.2633.899.9922.9829.1433.9736.456.6319.0021.8228.6530.04
ETN/MTX21.1430.6138.5742.1050.4927.5934.7342.9748.4654.4220.9030.8735.9239.6546.92

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Percent Change From Baseline in Duration (Minutes) of Morning Stiffness

The duration of morning stiffness on the day of examination should be determined by asking the following two questions: When did you awaken this morning? When were you able to resume your normal activities without stiffness? Duration of morning stiffness is equal to the time elapsed between the above two times in minutes; If none is present enter 0, If morning stiffness is still continuing, please indicate average of duration of stiffness over the past 3 days. If stiffness persists the entire day 1440 minutes (24h x 60 minutes) should be recorded. (NCT00422227)
Timeframe: Week 2, 4, 8, 12, 16

,
InterventionPercent change (Number)
Week 2Week 4Week 8Week 12Week 16
DMARD/MTX16.4333.2237.3552.7646.77
ETN/MTX54.9263.8573.4179.7680.55

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Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response

EULAR Response Criteria DAS28) improvement at week 16. Good response was defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders were participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >3.7. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response. (NCT00422227)
Timeframe: Week 16

InterventionPercentage of Participants (Number)
ETN/MTX87.82
DMARD/MTX73.79

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Percent Change From Baseline in DAS28 at Week 16

Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). (NCT00422227)
Timeframe: Week 16

InterventionPercent change (Number)
ETN/MTX38.32
DMARD/MTX27.46

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Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks

"ACR-N = the lowest of 3 values (percent change in the number of swollen joints, percent change in the number of tender joints, and median of the other 5 measures in the ACR core data set). Negative numbers indicate worsening.~The ACR-N AUC was calculated using the trapezoidal rule as the ACR-N multiplied by the duration of the assessment period (in weeks) and was presented as %-weeks." (NCT00422227)
Timeframe: 16 weeks

InterventionUnits on a scale (Mean)
ETN/MTX434.83
DMARD/MTX289.54

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Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2

Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). (NCT00422227)
Timeframe: Week 16

,
InterventionPercentage of Participants (Number)
≥0.6≥1.2
DMARD/MTX78.6466.02
ETN/MTX91.3782.74

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Percent Change From Baseline in Painful and Swollen Joint Counts

Participant's assessment of pain - A horizontal pain visual analog scale (VAS) (0-100 mm) is used to assess the participants current level of pain; 0 = no pain and 100 = worst pain. Swollen joint count - ACR swollen joint count, an assessment of 28 joints. Joints are classified as either swollen or not swollen. (NCT00422227)
Timeframe: Week 2, 4, 8, 12, 16

,
InterventionPercent change (Number)
Painful Joints - Week 2Painful Joints - Week 4Painful Joints - Week 8Painful Joints - Week 12Painful Joints - Week 16Swollen Joints - Week 2Swollen Joints - Week 4Swollen Joints - Week 8Swollen Joints - Week 12Swollen Joints - Week 16
DMARD/MTX27.6836.7149.7155.5557.3121.3227.7244.1950.4856.32
ETN/MTX34.1746.1155.4865.6568.9938.5949.3359.9167.9773.83

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Percent Change From Baseline in Physician And Subject Global Assessments

The Physician Global Assessment of Disease Activity: The participant's disease activity is estimated over the last two - three days by the physician; A zero (0) means no disease activity and a ten (10) means extreme disease activity. The Subject Global Assessment of Disease Activity: The participant assesses overall arthritis activity. A zero (0) means no disease activity and a ten (10) means extreme disease activity. (NCT00422227)
Timeframe: Week 2, 4, 8, 12, 16

,
InterventionPercent change (Number)
Physician Global Assessment - Week 2Physician Global Assessment - Week 4Physician Global Assessment - Week 8Physician Global Assessment - Week 12Physician Global Assessment - Week 16Subject Global Assessment - Week 2Subject Global Assessment - Week 4Subject Global Assessment - Week 8Subject Global Assessment - Week 12Subject Global Assessment - Week 16
DMARD/MTX11.8322.8135.4138.6745.047.2419.2226.0830.1030.55
ETN/MTX30.4039.5845.8655.0062.0521.8428.9434.9243.1850.76

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Percentage of Participants Achieving ACR 20, 50, and 70 Responses

Response includes improvement in tender or swollen joints as well as 20 percent improvement in three of the other five criteria. Required: ≥ 20%, 50% or 70% improvement in tender joint count ≥ 20% , 50% or 70% improvement in swollen joint count and at least 20%, 50%, 70% improvement in 3 of the following 5:Patient pain assessment , Patient global assessment ,Physician global assessment, Patient self-assessed disability. (NCT00422227)
Timeframe: Week 16

,
InterventionPercentage of Participants (Number)
ACR 20ACR 50ACR 70
DMARD/MTX58.1634.697.14
ETN/MTX78.8756.7019.07

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Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission)

Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm). (NCT00422227)
Timeframe: Week 16

,
InterventionPercentage of Participants (Number)
Low Disease (DAS28 <3.2)Remission (DAS28 <2.6)
DMARD/MTX18.457.77
ETN/MTX39.0915.74

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Percentage of Participants With a Reduction in the HAQ-DI Score

Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Percentage of Participants at Week 24Percentage of Participants at Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD52.350.5
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD58.551.8
Placebo x 2 IV + Non-Biologic DMARD32.923.1

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Percentage of Participants With EULAR Response Rates of Good/ Moderate

The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Week 24Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD54.258.8
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD61.060.3
Placebo x 2 IV + Non-Biologic DMARD31.424.9

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Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses

ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Percentage of Responders at Week 24Percentage of Responders at Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD42.248.7
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD47.950.7
Placebo x 2 IV + Non-Biologic DMARD2219.5

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Percentage of Participants With a Major Clinical Response

Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months. (NCT00476996)
Timeframe: Week 48

InterventionPercentage (Number)
Placebo x 2 IV + Non-Biologic DMARD1.8
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD4.0
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD5.7

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Change in DAS28 From Baseline

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionScore on a scale (Mean)
BaselineWeek 24Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD6.47-1.60-2.11
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD6.44-1.91-2.38
Placebo x 2 IV + Non-Biologic DMARD6.50-0.99-1.13

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Percentage of Participants Achieving an ACR50 Response

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP). (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Percentage of Participants at Week 24Percentage of Participants at Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD21.328.5
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD24.830.9
Placebo x 2 IV + Non-Biologic DMARD7.99

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Percentage of Participants Achieving an ACR70 Response

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Percentage of Participants at Week 24Percentage of Participants at Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD7.611.2
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD9.918.1
Placebo x 2 IV + Non-Biologic DMARD2.94.3

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Percentage of Participants Achieving Disease Activity Score (DAS28) Remission

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. (NCT00476996)
Timeframe: Weeks 24 and 48

,,
InterventionPercentage (Number)
Percentage of Participants at Week 24Percentage of Participants at Week 48
Ocrelizumab 200 mg x 2 + Non-Biologic DMARD5.811.9
Ocrelizumab 500 mg x 2 + Non-Biologic DMARD6.012.1
Placebo x 2 IV + Non-Biologic DMARD1.81.4

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Measuring the Safety and Efficacy of a New DMARD, Leflunomide Alone or in Combination With Traditional DMARD's. Participants Reaching ACR 20 Response. at 48 Weeks

"The combination of Methotrexate-Sulfasalazine-Hydroxychloroquine has been shown to be more effective than Methotrexate alone or the double combination of Methotrexate-Hydroxychloroquine. Primary outcome is ACR 20 response at 48 weeks.~An ACR 20 Response is a measure of at least 20% improvement in the number of tender and swollen joints. and a 20% improvement in at least 3 of the following:~the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function; the physician's global assessment of disease status; serum C-reactive protein levels." (NCT00579878)
Timeframe: 48 weeks

InterventionParticipants (Count of Participants)
1 Leflunomide Alone vs Combination Therapy8
Methotrexate-Sulfasalazine-Hydroxychloroquine20
Leflunomide-Sulfasalazine-Hydroxychloroquine12

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AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose (Per Participant) - Metabolite A77 1726

Bioequivalence based on AUC0-72 (NCT00834405)
Timeframe: Blood samples collected over 72 hour period

Interventionng*h/mL (Mean)
Leflunomide132584.730
Arava®123335.784

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Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma

Bioequivalence based on Cmax (NCT00834405)
Timeframe: Blood samples collected over 72 hour period

Interventionng/mL (Mean)
Leflunomide2488.000
Arava®2345.294

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AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose - Metabolite A77 1726

Bioequivalence based on AUC0-72 (NCT00834418)
Timeframe: Blood samples collected over 72 hour period

Interventionng*h/mL (Mean)
Leflunomide105806.888
Arava™103905.901

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Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma

Bioequivalence based on Cmax (NCT00834418)
Timeframe: Blood samples collected over 72 hour period

Interventionng/mL (Mean)
Leflunomide2109.286
Arava™1974.000

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Remission According to SDAI (Simple Disease Activity Index) at Week 16

"Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 16.~SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.~A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity." (NCT01172639)
Timeframe: week 16

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group42
CoBRA Slim High Risk Group33
CoBRA Avant-garde High Risk Group44
CoBRA Slim Low Risk Group12
Tight Step Up Low Risk Group12

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Remission According to DAS28-CRP at Week 52

"Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 52. (co-primary end point)~DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).~A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity." (NCT01172639)
Timeframe: week 52

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group63
CoBRA Slim High Risk Group57
CoBRA Avant-garde High Risk Group57
CoBRA Slim Low Risk Group29
Tight Step Up Low Risk Group29

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Remission According to DAS28-CRP at Week 16

"Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 16.~DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).~A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity." (NCT01172639)
Timeframe: week 16

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group69
CoBRA Slim High Risk Group72
CoBRA Avant-garde High Risk Group61
CoBRA Slim Low Risk Group25
Tight Step Up Low Risk Group23

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Remission According to DAS28-CRP at Week 104

"Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 104. (co-primary endpoints)~DAS28-CRP is calculated with the following formula : 0.56*SQRT TJC28+0.28*SQRT SJC28+0.36*ln (CRP+1)+0.014*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS).~A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity." (NCT01172639)
Timeframe: week 104

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group64
CoBRA Slim High Risk Group71
CoBRA Avant-garde High Risk Group69
CoBRA Slim Low Risk Group29
Tight Step Up Low Risk Group34

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Clinically Significant Change in HAQ Score

"Number of patients with a change of > 0.22 in the Health Assessment Questionnaire (HAQ) score over the period between baseline and week 104.~A change of > 0.22 in this score is considered as clinical relevant for rheumatoid arthritis patients." (NCT01172639)
Timeframe: Baseline-week104

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group71
CoBRA Slim High Risk Group62
CoBRA Avant-garde High Risk Group64
CoBRA Slim Low Risk Group25
Tight Step Up Low Risk Group26

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Remission According to SDAI at Week 52

"Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 52.~SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.~A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity." (NCT01172639)
Timeframe: week 52

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group36
CoBRA Slim High Risk Group27
CoBRA Avant-garde High Risk Group39
CoBRA Slim Low Risk Group20
Tight Step Up Low Risk Group15

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Remission According to SDAI at Week 104

"Number of patients in remission according to SDAI (Simplified Disease Activity Index) at week 104.~SDAI is calculated with the following formula : TJC28+SJC28+GH+GA ph in which TJC is the number of tender joints, SJC the number of Swollen Joint and GH the general health assessed by the patient on a Visual Analogue Scale (VAS) and GA ph the general assessment of the physician on a VAS.~A value below 3.3 is indicating remission, between 3.4 and 11.0 low disease activity, between 11.1 and 26.0 moderate disease activity and above 26.0 high disease activity." (NCT01172639)
Timeframe: week 104

InterventionParticipants (Count of Participants)
CoBRA Classic High Risk Group31
CoBRA Slim High Risk Group28
CoBRA Avant-garde High Risk Group41
CoBRA Slim Low Risk Group20
Tight Step Up Low Risk Group13

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DAS28 at 3 Weeks

"The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count.~The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 0-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease" (NCT01619176)
Timeframe: At 3 weeks

Interventionunits on a scale (Mean)
Acupuncture5
Control5.27

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DAS28 at 3 Months

"The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count.~The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 0-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease" (NCT01619176)
Timeframe: At 3 months

Interventionunits on a scale (Mean)
Acupuncture3.85
Control4.5

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ACR70 Response Rate at 3 Weeks

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to 3 weeks

InterventionParticipants (Count of Participants)
Acupuncture0
Control0

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ACR70 Response Rate at 3 Months

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to three months

InterventionParticipants (Count of Participants)
Acupuncture0
Control1

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ACR50 Response Rate at 3 Weeks

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to 3 weeks

InterventionParticipants (Count of Participants)
Acupuncture0
Control1

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ACR50 Response Rate at 3 Months

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to three months

InterventionParticipants (Count of Participants)
Acupuncture2
Control1

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ACR20 Response Rate at 3 Weeks

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to 3 weeks

InterventionParticipants (Count of Participants)
Acupuncture0
Control1

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DAS28 at Baseline

"The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count.~The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 2.6-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease" (NCT01619176)
Timeframe: At baseline

Interventionunits on a scale (Mean)
Acupuncture4.98
Control6.8

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ACR20 Response Rate at 3 Months

"ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters:~acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire~The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)" (NCT01619176)
Timeframe: From baseline to three months

InterventionParticipants (Count of Participants)
Acupuncture5
Control3

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Change From Baseline in EQ-5D-3L VAS Scores at Week 12

The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w8.39
Sarilumab 150 mg q2w17.16
Sarilumab 200 mg q2w15.23

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Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.970
Sarilumab 150 mg q2w-3.096
Sarilumab 200 mg q2w-3.269

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Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24

"ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 no pain to 100 worst pain. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate." (NCT01709578)
Timeframe: Baseline, Week 12 and Week 24

,,
Interventionmm (Least Squares Mean)
Physician global VAS at week 12Participant global VAS at week 12Pain VAS at week 12Physician global VAS at week 24Participant global VAS at week 24Pain VAS at week 24
Placebo q2w-22.74-13.75-15.13-28.55-19.76-21.27
Sarilumab 150 mg q2w-33.64-25.28-26.93-40.65-29.59-31.90
Sarilumab 200 mg q2w-35.44-27.38-30.56-43.22-31.28-33.65

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Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12 and Week 24

,,
Interventionunits on a scale (Least Squares Mean)
HAQ-DI at week 12HAQ-DI at week 24
Placebo q2w-0.26-0.34
Sarilumab 150 mg q2w-0.46-0.52
Sarilumab 200 mg q2w-0.47-0.58

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Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24

"ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific marker for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate." (NCT01709578)
Timeframe: Baseline, Week 12 and Week 24

,,
Interventionmg/L (Least Squares Mean)
CRP at week 12CRP at week 24
Placebo q2w-3.63-3.60
Sarilumab 150 mg q2w-15.08-15.24
Sarilumab 200 mg q2w-22.98-23.27

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Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. (NCT01709578)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Placebo q2w33.7
Sarilumab 150 mg q2w55.8
Sarilumab 200 mg q2w60.9

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Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. (NCT01709578)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Placebo q2w7.2
Sarilumab 150 mg q2w24.9
Sarilumab 200 mg q2w28.8

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Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. (NCT01709578)
Timeframe: Week 12

InterventionPercentage of participants (Number)
Placebo q2w3.9
Sarilumab 150 mg q2w17.1
Sarilumab 200 mg q2w17.9

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Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.38
Sarilumab 150 mg q2w-2.35
Sarilumab 200 mg q2w-2.82

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Change From Baseline in DAS28-CRP at Week 12

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-0.97
Sarilumab 150 mg q2w-2.13
Sarilumab 200 mg q2w-2.45

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Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-16.35
Sarilumab 150 mg q2w-23.65
Sarilumab 200 mg q2w-26.08

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Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24

SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w4.40
Sarilumab 150 mg q2w7.65
Sarilumab 200 mg q2w8.48

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Percentage of Participants Achieving ACR70 Criteria at Week 24

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. (NCT01709578)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Placebo q2w7.2
Sarilumab 150 mg q2w19.9
Sarilumab 200 mg q2w16.3

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Percentage of Participants Achieving ACR50 Criteria at Week 24

ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. (NCT01709578)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Placebo q2w18.2
Sarilumab 150 mg q2w37.0
Sarilumab 200 mg q2w40.8

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Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.632
Sarilumab 150 mg q2w-2.422
Sarilumab 200 mg q2w-2.727

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Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-3.50
Sarilumab 150 mg q2w-6.13
Sarilumab 200 mg q2w-6.18

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Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-3.64
Sarilumab 150 mg q2w-4.26
Sarilumab 200 mg q2w-4.34

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Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-1.60
Sarilumab 150 mg q2w-3.87
Sarilumab 200 mg q2w-3.86

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Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-3.36
Sarilumab 150 mg q2w-4.60
Sarilumab 200 mg q2w-4.88

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Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-1.97
Sarilumab 150 mg q2w-3.51
Sarilumab 200 mg q2w-4.12

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Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-1.20
Sarilumab 150 mg q2w-1.97
Sarilumab 200 mg q2w-2.98

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Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.043
Sarilumab 150 mg q2w-1.924
Sarilumab 200 mg q2w-1.873

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Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.210
Sarilumab 150 mg q2w-2.772
Sarilumab 200 mg q2w-2.404

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Change From Baseline in SF-36 MCS at Week 24

SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w4.74
Sarilumab 150 mg q2w6.26
Sarilumab 200 mg q2w6.76

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Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-2.10
Sarilumab 150 mg q2w-5.52
Sarilumab 200 mg q2w-5.54

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Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-1.69
Sarilumab 150 mg q2w-4.24
Sarilumab 200 mg q2w-3.20

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Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-0.77
Sarilumab 150 mg q2w-3.07
Sarilumab 200 mg q2w-2.94

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Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-2.60
Sarilumab 150 mg q2w-3.97
Sarilumab 200 mg q2w-3.98

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Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

InterventionDays (Least Squares Mean)
Placebo q2w-2.23
Sarilumab 150 mg q2w-2.53
Sarilumab 200 mg q2w-3.26

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Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

InterventionDays (Least Squares Mean)
Placebo q2w-2.01
Sarilumab 150 mg q2w-2.87
Sarilumab 200 mg q2w-3.19

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Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12

Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-0.26
Sarilumab 150 mg q2w-0.46
Sarilumab 200 mg q2w-0.47

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Change From Baseline in RAID Scores at Week 12

RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Mean)
Placebo q2w-1.34
Sarilumab 150 mg q2w-2.27
Sarilumab 200 mg q2w-2.47

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Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24

The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w6.82
Sarilumab 150 mg q2w9.86
Sarilumab 200 mg q2w10.06

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Change From Baseline in the FACIT-fatigue at Week 12

The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Placebo q2w5.56
Sarilumab 150 mg q2w8.02
Sarilumab 200 mg q2w9.45

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Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24

RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-1.80
Sarilumab 150 mg q2w-2.55
Sarilumab 200 mg q2w-2.80

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Change From Baseline in Morning Stiffness VAS at Week 24

RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionmm (Least Squares Mean)
Placebo q2w-21.66
Sarilumab 150 mg q2w-32.30
Sarilumab 200 mg q2w-33.79

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Change From Baseline in HAQ-DI at Week 24

Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w-0.34
Sarilumab 150 mg q2w-0.52
Sarilumab 200 mg q2w-0.58

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Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24

The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate. (NCT01709578)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo q2w14.85
Sarilumab 150 mg q2w20.06
Sarilumab 200 mg q2w18.40

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Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12 and Week 24

,,
Interventionjoints (Least Squares Mean)
TJC at week 12SJC at week 12TJC at week 24SJC at week 24
Placebo q2w-8.55-6.75-10.55-8.19
Sarilumab 150 mg q2w-13.74-10.54-14.44-11.56
Sarilumab 200 mg q2w-14.87-10.59-16.95-11.94

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Change From Baseline in SF-36 at Week 12

SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate. (NCT01709578)
Timeframe: Baseline, Week 12

,,
Interventionunits on a scale (Least Squares Mean)
Physical Component Summary Score at Week 12Mental Component Summary Score at Week 12
Placebo q2w3.743.50
Sarilumab 150 mg q2w6.935.14
Sarilumab 200 mg q2w6.846.47

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Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. (NCT01709578)
Timeframe: Week 12

,,
InterventionPercentage of participants (Number)
ACR20ACR50ACR70
Placebo q2w37.613.32.2
Sarilumab 150 mg q2w54.130.413.8
Sarilumab 200 mg q2w62.533.214.7

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Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment. All adverse events that occurred from the first dose of the study drug administration up to 60 days after the end of treatment visit were considered as TEAEs. Serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. A summary of SAEs, all other non-serious AEs, regardless of causality, are reported in AE section. (NCT01768572)
Timeframe: Up to 211 days

,,
Interventionparticipants (Number)
Any TEAEAny treatment-emergent SAEAny TEAE leading to deathAny TEAE leading to discontinuation
Sarilumab 150 mg q2w33106
Sarilumab 200 mg q2w36308
Tocilizumab q4w68714

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Tocilizumab Serum Levels

(NCT01941095)
Timeframe: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

Interventionmicrogrms per milliliter (mcg/mL) (Mean)
Week 1Week 12Week 24Week 36Week 52Week 60
Tocilizumab0.3841.9844.6747.9045.376.46

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Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24

DAS28-ESR score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), patient global assessment of disease activity (PGA) (general health [GH]) using visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in millimeters per hour [mm/hr]). The score is calculated using the following formula: DAS28-ESR = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score of less than (<) 2.6 represents DAS28-ESR remission. (NCT01941095)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Tocilizumab40

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Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation

(NCT01941095)
Timeframe: From Baseline up to Week 52

Interventionpercentage of participants (Number)
Tocilizumab48.6

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Change From Baseline in DAS28-ESR up to Week 52

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. A negative change from baseline indicates an improvement. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionunits on a scale (Mean)
Change at Week 2Change at Week 4Change at Week 8Change at Week 12Change at Week 16Change at Week 20Change at Week 24Change at Week 28Change at Week 32Change at Week 36Change at Week 40Change at Week 44Change at Week 48Change at Week 52
Tocilizumab-0.99-1.70-2.20-2.56-2.59-2.93-3.14-3.22-3.34-3.32-3.40-3.45-3.42-3.40

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Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52

SDAI is an index for measuring disease activity. SDAI is the numerical sum of five outcome parameters: TJC28 and SJC28, PGA and physician global assessment of disease activity assessed on VAS (0 centimeter [cm]-10 cm); 0 cm= no disease activity and 10 cm= worst disease activity, and CRP (in milligrams per deciliter [mg/dL]). SDAI total score ranges from 0 to 86, with higher scores indicating increased (or severe) disease activity. SDAI score 3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionunits on a scale (Mean)
Change at Week 2Change at Week 4Change at Week 8Change at Week 12Change at Week 16Change at Week 20Change at Week 24Change at Week 28Change at Week 32Change at Week 36Change at Week 40Change at Week 44Change at Week 48Change at Week 52
Tocilizumab-3.41-6.54-8.72-11.07-13.47-13.88-14.08-15.37-16.09-15.61-14.86-16.31-16.47-17.35

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Change From Baseline in SJC28 up to Week 52

28 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28. A negative change from baseline indicated improvement. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionswollen joints (Mean)
Change at Week 2Change at Week 4Change at Week 8Change at Week 12Change at Week 16Change at Week 20Change at Week 24Change at Week 28Change at Week 32Change at Week 36Change at Week 40Change at Week 44Change at Week 48Change at Week 52
Tocilizumab-1.82-3.08-4.71-5.24-5.79-6.06-6.60-6.65-6.73-6.76-6.91-6.82-6.63-6.98

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Change From Baseline in TJC28 up to Week 52

28 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28. A negative change from baseline indicated improvement. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventiontender joints (Mean)
Change at Week 2Change at Week 4Change at Week 8Change at Week 12Change at Week 16Change at Week 20Change at Week 24Change at Week 28Change at Week 32Change at Week 36Change at Week 40Change at Week 44Change at Week 48Change at Week 52
Tocilizumab-1.30-3.26-4.97-5.82-6.39-7.03-7.72-7.91-8.38-8.28-8.22-8.63-8.26-8.75

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Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score

FACIT-Fatigue total score is sum of FACIT-General subscale score and FACIT-Fatigue (additional concerns) subscale score. FACT-General consists of 27 questions grouped in 4 domains of general health-related quality of life: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-General score ranges between 0-108. FACIT-Fatigue subscale is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). For all items, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue subscale score for a total possible score of 0 (worse score) to 52 (better score). FACIT-Fatigue total score (FACT-G plus FACT-F subscale scores) ranges from 0 (better score) to 160 (worse score). (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionunits on a scale (Mean)
Week 1Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab89.6891.83100.38103.16106.39110.17112.60114.21114.85117.01116.50116.59119.67119.83121.82

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HAQ-DI Score

"The Stanford HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Responses in each component set were scored from 0 (without any difficulty) to 3 (unable to do). The highest score recorded for any question in a category determines the score for the category, unless aids, devices, or help from another person was required. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3. Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 as moderate to severe disability, and 2 to 3 as severe to very severe disability." (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionunits on a scale (Mean)
Week 1Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab1.311.221.090.910.820.720.680.660.660.590.630.600.590.560.54

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Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation

Reasons for corticosteroid dose reduction included: Safety Reasons (including elevated liver function test results, respiratory infections, infections and infestations, gastrointestinal disorders etc.); Other Reasons (disease remission, improvement etc.); and Unknown Reasons (including no reason). Number of participants by reasons (Safety, Other, Unknown) for corticosteroid dose reduction or discontinuation were reported. (NCT01941095)
Timeframe: From Baseline up to Week 52

Interventionparticipants (Number)
SafetyOtherUnknown
Tocilizumab6102

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Number of Participants With American College of Rheumatology 20 (ACR20) Response

ACR20 response was defined as >/=20% improvement from baseline in both TJC28 and SJC28 as well as in 3 out of 5 additional parameters: Separate patient and physician's global assessment of disease activity on VAS (0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS), patient's assessment of pain on VAS (0 mm=no pain to 100 mm=unbearable pain, displayed on the 100 mm horizontal VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without any difficulty to 3=unable to do), and acute phase response (ESR in mm/hr, for a total possible score of 0 to 10). (NCT01941095)
Timeframe: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionparticipants (Number)
Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab19192391316913101110121315

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Number of Participants With Anti-Tocilizumab Antibodies (ATA)

All samples were tested using a screening assay and, if positive, by a confirmation assay to determine specificity and a neutralizing assay to test for the ability to inhibit the activity of tocilizumab. Number of participants with a positive assay result for screening assay (ATA - Screen), confirmatory assay (ATA - Confirmatory), and neutralizing assay (ATA - Neutralizing) was reported separately. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

Interventionparticipants (Number)
Week 1: ATA - ScreenWeek 1: ATA - ConfirmatoryWeek 1: ATA - NeutralizingWeek 12: ATA - ScreenWeek 12: ATA - ConfirmatoryWeek 12: ATA - NeutralizingWeek 24: ATA - ScreenWeek 24: ATA - ConfirmatoryWeek 24: ATA - NeutralizingWeek 36: ATA - ScreenWeek 36: ATA - ConfirmatoryWeek 36: ATA - NeutralizingWeek 52: ATA - ScreenWeek 52: ATA - ConfirmatoryWeek 52: ATA - NeutralizingWeek 60: ATA - ScreenWeek 60: ATA - ConfirmatoryWeek 60: ATA - Neutralizing
Tocilizumab740300311200200110

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Patient Assessment of Pain, Using VAS Score

"The participant's level of pain was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no pain and the extreme right end = 100 mm, and was described as unbearable pain. Higher values correspond to worst state of participant (higher level of pain)." (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionmm (Mean)
Week 1Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab46.4052.0449.8742.7237.2134.2431.0029.5729.6325.5026.7827.5026.8823.6123.98

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Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score <2.6 represents DAS28-ESR remission. DAS28-ESR score greater than or equal to (>/=) 2.6 and <3.2 represents LDA. (NCT01941095)
Timeframe: Weeks 28, 32, 36, 40, 44, 48, 52

Interventionpercentage of participants (Number)
Week 28: RemissionWeek 32: RemissionWeek 36: RemissionWeek 40: RemissionWeek 44: RemissionWeek 48: RemissionWeek 52: RemissionWeek 28: LDAWeek 32: LDAWeek 36: LDAWeek 40: LDAWeek 44: LDAWeek 48: LDAWeek 52: LDA
Tocilizumab5.18.14.19.56.98.567.61.46.86.86.94.29

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Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24

DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = [0.56 * √TJC28 + [0.28*√SJC28]+[0.70*ln ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score <2.6 represents DAS28-ESR remission. The percentage reported for Week 24 is based on confirmation on switching to SC tocilizumab monotherapy. (NCT01941095)
Timeframe: Weeks 24, 28, 32, 36, 40, 44, 48, 52

Interventionpercentage of participants (Number)
Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab38.734.236.536.536.535.235.738.8

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Percentage of Participants Who Received All Planned Study Medication (Compliance)

Compliance (in terms of percentage of participants who received all planned study medication) was assessed on the basis of participant diary cards and return records. (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionpercentage of participants (Number)
Week 1Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab6697.910010098.997.698.8100100100100100100100100

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Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria

Response to treatment was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the baseline visit. Participants with a score lesser than or equal to () 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score 0.6 to 5.1 with reduction of >0.6 to NCT01941095)
Timeframe: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionpercentage of participants (Number)
Week 2: Good responseWeek 2: Moderate responseWeek 2: No responseWeek 4: Good responseWeek 4: Moderate responseWeek 4: No responseWeek 8: Good responseWeek 8: Moderate responseWeek 8: No responseWeek 12: Good responseWeek 12: Moderate responseWeek 12: No responseWeek 16: Good responseWeek 16: Moderate responseWeek 16: No responseWeek 20: Good responseWeek 20: Moderate responseWeek 20: No responseWeek 24: Good responseWeek 24: Moderate responseWeek 24: No responseWeek 28: Good responseWeek 28: Moderate responseWeek 28: No responseWeek 32: Good responseWeek 32: Moderate responseWeek 32: No responseWeek 36: Good responseWeek 36: Moderate responseWeek 36: No responseWeek 40: Good responseWeek 40: Moderate responseWeek 40: No responseWeek 44: Good responseWeek 44: Moderate responseWeek 44: No responseWeek 48: Good responseWeek 48: Moderate responseWeek 48: No responseWeek 52: Good responseWeek 52: Moderate responseWeek 52: No response
Tocilizumab9.444.845.89.538.951.610.823.665.69.220.770.15.915.378.86.126.867.16.221.272.66.311.482.3018.981.11.314.983.85.417.6772.813.983.35.711.482.99460

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PGA, Using VAS Score

"PGA was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end = 100 mm, and was described as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity)." (NCT01941095)
Timeframe: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Interventionmm (Mean)
Week 1Week 2Week 4Week 8Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Tocilizumab28.2627.5728.3632.2828.7324.4028.1532.6326.0227.0830.7930.5025.7923.8623.08

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Soluble Interleukin-6 Receptor (sIL-6R) Levels

(NCT01941095)
Timeframe: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)

Interventionnanograms per milliliter (ng/mL) (Mean)
Week 1Week 12Week 24Week 36Week 52Week 60
Tocilizumab39450553.43572.03570.78537.7342850

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Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab

AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). (NCT02057250)
Timeframe: Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85

,,,
Interventionmg*day/L (Mean)
Week 0-2Week 10-12
Sarilumab 150 mg by AID (AID Assessment Phase)131205
Sarilumab 150 mg by PFS (AID Assessment Phase)152220
Sarilumab 200 mg by AID (AID Assessment Phase)235455
Sarilumab 200 mg by PFS (AID Assessment Phase)227405

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Number of Validated AID Associated Product Technical Failures (PTFs)

"A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each participant was given a diary having questions related to participant's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Participants were asked to answer the questions each time they self-inject the sarilumab. If the response was no to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF." (NCT02057250)
Timeframe: Baseline up to Week 12

InterventionPTFs (Number)
Sarilumab 150 mg by AID (AID Assessment Phase)0
Sarilumab 200 mg by AID (AID Assessment Phase)0

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Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

"Criteria for potentially clinically significant vital sign abnormalities:~Systolic blood pressure (SBP) supine: <=95 mmHg and decrease from baseline (DFB) >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg~Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB ≥10 mmHg~SBP (Orthostatic): <=-20 mmHg~DBP (Orthostatic): <=-10 mmHg~Heart rate (HR) supine: <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm~Weight: >=5% DFB; >=5% IFB" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
SBP (supine) <=95 mmHg and DFB >=20 mmHgSBP (supine) >=160 mmHg and IFB >=20 mmHgDBP (supine) <=45 mmHg and DFB >=10 mmHgDBP (supine) >=110 mmHg and IFB >=10 mmHgSBP (orthostatic) <=-20 mmHgDBP (orthostatic) <=-10 mmHgHR (supine) <=50 bpm and DFB >= 20 bpmHR (supine) >=120 bpm and IFB >=20 bpmWeight >=5% DFBWeight >=5% IFB
Sarilumab 150 mg q2w01005510212
Sarilumab 150 mg q2w + DMARDs0100830013
Sarilumab 200 mg q2w01009101007
Sarilumab 200 mg q2w + DMARDs0100530012

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Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52

ACR response is a composite rating scale that includes 7 variables: tender joints count (TJC [68 joints]); swollen joints count (SJC [66 joints]); levels of an acute phase reactant (high sensitivity C-reactive protein [hs-CRP level]); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] visual analog scale [VAS]); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by Health Assessment Question-Disability Index [HAQ-DI], with scoring range of 0 [better health] - 3 [worst health]). ACR20/50/70 response is defined as at least 20/50/70% improvement in both TJC and SJC, and at least 20/50/70% improvement in at least 3 of the 5 other assessments, respectively. (NCT02373202)
Timeframe: Week 52

,,,
Interventionpercentage of participants (Number)
ACR20ACR50ACR70
Sarilumab 150 mg q2w76.756.726.7
Sarilumab 150 mg q2w + DMARDs73.360.053.3
Sarilumab 200 mg q2w74.254.825.8
Sarilumab 200 mg q2w + DMARDs40.033.326.7

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Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Adverse event (AE) was defined as any untoward medical occurrence in a participant who received IMP and did not necessary have to had a causal relationship with treatment. All AEs that occurred from the first dose of the IMP administration up to 6 weeks after last dose of treatment (up to Week 58) were considered as TEAEs. SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. TEAEs included both SAEs and non-SAEs. (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
Any TEAESAE
Sarilumab 150 mg q2w251
Sarilumab 150 mg q2w + DMARDs140
Sarilumab 200 mg q2w282
Sarilumab 200 mg q2w + DMARDs133

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Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52

HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each items's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. (NCT02373202)
Timeframe: Baseline, Week 52

Interventionunits on a scale (Mean)
Sarilumab 150 mg q2w + DMARDs-0.52
Sarilumab 200 mg q2w + DMARDs-0.34
Sarilumab 150 mg q2w-0.48
Sarilumab 200 mg q2w-0.38

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Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP)

DAS28-CRP is a composite score that contains 4 variables: TJC (based on 28 joints), SJC (based on 28 joints), participant's assessment of general health on VAS (range 0 [very well] to 100 mm [extremely bad]) and CRP (mg/L). DAS28-CRP total score ranges from 2-10 with a lower score indicating less disease activity. A DAS28-CRP above 5.1 indicates high disease activity, whereas below 3.2 indicates low disease activity and below 2.6 as disease remission. (NCT02373202)
Timeframe: Baseline, Week 52

Interventionunits on a scale (Mean)
Sarilumab 150 mg q2w + DMARDs-2.90
Sarilumab 200 mg q2w + DMARDs-2.47
Sarilumab 150 mg q2w-2.62
Sarilumab 200 mg q2w-2.64

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Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities

"Criteria for potentially clinically significant ECG abnormalities:~PR Interval: >200 milliseconds (ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%~QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%~QT Interval: >500 ms~QTc Bazett (QTc B): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms, IFB >60 ms~QTc Fridericia (QTc F): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
PR >200 msPR >200 ms and IFB >=25%PR >220 msPR >220 ms and IFB >=25%PR >240 msPR >240 ms and IFB >=25%QRS >110 msQRS >110 ms and IFB >=25%QRS >120 msQRS >120 ms and IFB >=25%QT >500 msQTc B >450 msQTc B >480 msQTc B >500 msQTc B IFB >30 and <=60 msQTc B IFB >60 msQTc F >450 msQTc F >480 msQTc F >500 msQTc F IFB >30 and <=60 msQTc F IFB >60 ms
Sarilumab 150 mg q2w000000000006002020000
Sarilumab 150 mg q2w + DMARDs000000000002000020000
Sarilumab 200 mg q2w1010001000110101061000
Sarilumab 200 mg q2w + DMARDs000000202001101010000

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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes

"Criteria for potentially clinically significant abnormalities:~Sodium: <=129 mmol/L; >=160 mmol/L~Potassium: <3 mmol/L; >=5.5 mmol/L~Chloride: <80 mmol/L; >115 mmol/L" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
Sodium <=129 mmol/LSodium >=160 mmol/LPotassium <3 mmol/LPotassium >=5.5 mmol/LChloride <80 mmol/LChloride >115 mmol/L
Sarilumab 150 mg q2w000000
Sarilumab 150 mg q2w + DMARDs000000
Sarilumab 200 mg q2w000000
Sarilumab 200 mg q2w + DMARDs000000

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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters

"Criteria for potentially clinically significant abnormalities:~Hemoglobin: <=115 g/L (Male[M]) or <=95 g/L (Female[F]); >=185 g/L (M) or >=165 g/L (F); DFB >=20 g/L~Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F); >=0.55 v/v (M) or >=0.5 v/v (F)~Red blood cells (RBC): >=6 Tera/L~Platelets: <50 Giga/L; >=50 and <100 Giga/L; >=700 Giga/L~White blood cells (WBC): <3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]); >=16.0 Giga/L~Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); <1.0 Giga/L~Lymphocytes: <0.5 Giga/L; >=0.5 Giga/L and 4.0 Giga/L~Monocytes: >0.7 Giga/L~Basophils: >0.1 Giga/L~Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L)" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
Hemoglobin <=115 g/L (M) or <=95 g/L (F)Hemoglobin >=185 g/L (M) or >=165 g/L (F)Hemoglobin DFB >=20 g/LHematocrit <=0.37 v/v (M) or <=0.32 v/v (F)Hematocrit >0.55 v/v (M) or >=0.5 v/v (F)RBC >=6 Tera/LPlatelets <50 Giga/LPlatelets >=50 and <100 Giga/LPlatelets >=700 Giga/LWBC <3.0 Giga/L (NB) or <2.0 Giga/L (B)WBC >=16.0 Giga/LNeutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)Neutrophils <1.0 Giga/LLymphocytes <0.5 Giga/LLymphocytes >=0.5 Giga/L and Lymphocytes >4.0 Giga/LMonocytes >0.7 Giga/LBasophils >0.1 Giga/LEosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L)
Sarilumab 150 mg q2w1002000107082030302
Sarilumab 150 mg q2w + DMARDs0000000106085030110
Sarilumab 200 mg q2w30260000090134180252
Sarilumab 200 mg q2w + DMARDs10030001090113041000

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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

"Criteria for potentially clinically significant abnormalities:~Alanine Aminotransferase (ALT): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN~Aspartate aminotransferase (AST): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN~Alkaline phosphatase: >1.5 ULN~Total bilirubin (TBILI): >1.5 ULN; >2 ULN~Conjugated bilirubin(CBILI): >1.5 ULN~Unconjugated bilirubin: >1.5 ULN~ALT >3 ULN and TBILI >2 ULN~CBILI >35% TBILI and TBILI >1.5 ULN~Albumin: <=25 g/L" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
ALT >1 ULN and <=1.5 ULNALT >1.5 ULN and <=3 ULNALT >3 ULN and <=5 ULNALT >5 ULN and <=10 ULNALT >10 ULN and <=20 ULNALT >20 ULNAST >1 ULN and <=1.5 ULNAST >1.5 ULN and <=3 ULNAST >3 ULN and <=5 ULNAST >5 ULN and <=10 ULNAST >10 ULN and <=20 ULNAST >20 ULNAlkaline Phosphatase >1.5 ULNTBILI >1.5 ULNTBILI >2 ULNCBILI >1.5 ULNUnconjugated Bilirubin >1.5 ULNALT> 3 ULN and TBILI >2ULNCBILI >35% TBILI and TBILI >1.5 ULNAlbumin <=25 g/L
Sarilumab 150 mg q2w73100082000000000000
Sarilumab 150 mg q2w + DMARDs32110061100001000000
Sarilumab 200 mg q2w62400043100000000000
Sarilumab 200 mg q2w + DMARDs41000050000001000000

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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

"Criteria for potentially clinically significant abnormalities:~Glucose: <=3.9 mmol/L and =11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas])~Hemoglobin A1c (HbA1c): >8%~Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L~LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L~Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
Glucose <=3.9 mmol/L and Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)HbA1c >8%Total Cholesterol >=6.2 mmol/LTotal Cholesterol >=7.74 mmol/LLDL Cholesterol >=4.1 mmol/LLDL Cholesterol >=4.9 mmol/LTriglycerides >=4.6 mmol/LTriglycerides >=5.6 mmol/L
Sarilumab 150 mg q2w1001216200
Sarilumab 150 mg q2w + DMARDs000611000
Sarilumab 200 mg q2w1211323111
Sarilumab 200 mg q2w + DMARDs010713100

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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters

"Criteria for potentially clinically significant abnormalities:~Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline~Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min~Blood urea nitrogen: >=17 mmol/L~Uric acid: <120 micromol/L; >408 micromol/L" (NCT02373202)
Timeframe: Baseline up to Week 58

,,,
Interventionparticipants (Number)
Creatinine >=150 micromol/L (Adults)Creatinine >=30% change from baselineCreatinine >=100% change from baselineCreatinine Clearance <15 mL/minCreatinine clearance >=15 to <30 mL/minCreatinine clearance >=30 to <60 mL/minCreatinine clearance >=60 to <90 mL/minBlood Urea Nitrogen >=17 mmol/LUric acid <120 micromol/LUric acid >408 micromol/L
Sarilumab 150 mg q2w06000615002
Sarilumab 150 mg q2w + DMARDs0300068001
Sarilumab 200 mg q2w15000517004
Sarilumab 200 mg q2w + DMARDs0300067011

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Response Duration

Median and range of nine patients with Complete Response (CR) (NCT02509052)
Timeframe: Assessed up to 48 months

Interventiondays (Median)
Arm 1: 20 mg Leflunomide336
Arm 2: 40 mg Leflunomide112
Arm 3: 60 mg Leflunomide54

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MTD, Defined as the Highest Dose in Which =< 1/6 Patients Experience a Dose-limiting Toxicity, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03

Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome. (NCT02509052)
Timeframe: 28 days

Interventionmg (Number)
All Participants60

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Clinical Benefit Response Rate (sCR/CR/VGPR/Partial Response [PR]/Minimal Response [MR] or Stable Disease [SD]), Assessed by IMWG Criteria

Clinical benefit response rate (sCR/CR/VGPR/partial response [PR]/minimal response [MR] or stable disease [SD]), assessed by International Myeloma Working Group (IMWG) criteria (NCT02509052)
Timeframe: From the start of treatment until disease progression/recurrence, assessed up to 48 months

InterventionParticipants (Count of Participants)
Arm 1: 20 mg Leflunomide3
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide3

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Best Overall Response Rate: Proportion of Patients Reaching CR by IMWG Criteria

Stringent complete response [sCR]/complete response [CR]/very good partial response [VGPR]/or partial response [PR]), assessed by International Myeloma Working Group (IMWG) criteria. (NCT02509052)
Timeframe: From the start of treatment until disease progression/recurrence, assessed up to 48 months

InterventionParticipants (Count of Participants)
Arm 1: 20 mg Leflunomide3
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide3

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Response Duration

Number of patients with Stable Disease greater than or equal to 90 days (NCT02509052)
Timeframe: Assessed at ninety days.

InterventionParticipants (Count of Participants)
Arm 1: 20 mg Leflunomide2
Arm 2: 40 mg Leflunomide3
Arm 3: 60 mg Leflunomide0

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Indian Health Assessment Questionnaire (iHAQ)

Indian version of Health assessment Questionnaire (iHAQ) Comprises of 12 questions relating to functional activity iHAQ score ranges from 0 to 3 (minimum 0, maximum 3) Higher scores indicate more disability (NCT02930343)
Timeframe: 12 weeks

Interventionscore on a scale (Median)
Group 1- MTX+LEF+HCQ0.7
Group 2- MTX+SSZ+HCQ0.5

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Number of Participants With Adverse Drug Reactions

Infections, transaminitis, nausea, vomiting, derranged renal function tests etc (NCT02930343)
Timeframe: 24 weeks

,
InterventionParticipants (Count of Participants)
Total number of any adverse eventsSerious adverse eventsAny gastrointestinal adverse reactionNauseaDiarrheaSwitch to parenteral MethotrexateRaised liver enzymes > 2 times upper limit normalHerpes labialisupper respiratory tract infectionurinary tract infectionHypertensionhairfallCytopenia
Group 1- MTX+LEF+HCQ150114151051120
Group 2- MTX+SSZ+HCQ2101661141250020

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Disease Activity as Per Ultrasound-7 (US-7) Score

Ultrasound 7 score (US-7) Calculates ultrasound score in 7 joints using greyscale and power doppler to evaluate for disease activity (synovitis, tenosynovitis) and damage (erosions) Score minimum value= 0 Maximum value = 108 Higher score indicates worse disease (NCT02930343)
Timeframe: 12 weeks

Interventionunits on a scale (Median)
Group 1- MTX+LEF+HCQ3.5
Group 2- MTX+SSZ+HCQ4

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Number of Patients Achieving Good EULAR Response at the End of 12 Weeks

"EULAR response criteria for Rheumatoid arthritis includes- estimation of DAS 28 ESR, that includes-~Tender joint count 28~Swollen joint count 28~ESR~Patient global assessment of health" (NCT02930343)
Timeframe: 12 weeks

Interventionparticipants (Number)
Group 1- MTX+LEF+HCQ40
Group 2- MTX+SSZ+HCQ37

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Multidimensional Assessment of Thymic States (MAThyS) Scale Total Score at Baseline, Weeks 4, 12 and 24

MAThyS was a multi-dimensional self-administered questionnaire comprised of five dimensions (emotional reactivity, cognition speed, psychomotor function, motivation and sensory perception) divided into 20 items relating to individual states as perceived by participants for the preceding week (at each specified Week). Each item was measured on a visual analog scale (VAS; in centimeters [cm]) ranged from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state). Total MAThyS score was sum of the 20 items and that might vary from score range 0 to 200 with lower scores indicated general inhibition and higher scores indicated general excitation. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventioncm (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab88.489.694.890.9

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International Physical Activity Questionnaire (IPAQ) Total Score at Baseline, Weeks 4, 12 and 24

IPAQ was a 27-item self-reported questionnaire designed to measure physical activity of participant. The score was reported in metabolic equivalent (MET)-minutes per week. MET minutes represented the amount of energy expended to carry out physical activity. For IPAQ total score, the minimum value is zero and there is no maximum. Higher scores mean better levels of physical activity. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

InterventionMET minutes per week (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab1759.91881.12061.02089.5

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Hospital Anxiety and Depression Scale (HADS): Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Baseline, Weeks 4, 12, and 24

HADS questionnaire measures the presence and severity of anxiety and depression in both hospital and community settings. The questionnaire comprised of 14 items divided into 2 subscales: 7 items for anxiety subscale (HADS-A) and 7 items for depression subscale (HADS-D). Each item was scored on a 0 to 3 rating scale. The anxiety and depression subscales each ranged from 0 to 21 (0-7: normal, 8-10: borderline abnormal and 11-21: abnormal), where higher scores indicated greater severity of anxiety/depression. The subscales were independent for each result of depression and anxiety. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
HADS-A: BaselineHADS-A: Week 4HADS-A: Week 12HADS-A: Week 24HADS-D: BaselineHADS-D: Week 4HADS-D: Week 12HADS-D: Week 24
Sarilumab8.17.26.16.67.06.65.75.5

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Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Scores at Baseline, Weeks 4, 12 and 24

FACIT-F was a 13-item questionnaire that assess fatigue in participants under chronic illness therapy. Participants scored each item on a 5-point Likert scale ranged from 0 to 4 (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The scores of each item were reversed during score calculations, so that higher score values indicated more favorable conditions. Total score was the sum of score from each item and resulted in a score range from 0 to 52, with higher score indicated better participant health status (lower level of fatigue). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab25.521.018.817.9

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Erythrocyte Sedimentation Rate (ESR) at Baseline, Weeks 4, 12, and 24

ESR was a laboratory test to provide non-specific measure of inflammation in the body. The test assessed the rate at which red blood cells fell in a test tube and was measured in millimeter per hour (mm/h). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionmm/h (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab28.810.59.28.4

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Duration of Morning Stiffness at Baseline, Weeks 4, 12, and 24

Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. At each specified time point, duration of morning stiffness was reported by the participant during the visit. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionminutes (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab72.334.728.921.3

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Change From Baseline in Stanford Health Assessment Questionnaire Disability Index Total Score at Weeks 4, 12 and 24

HAQ-DI was a participant-oriented questionnaire developed specifically to assess the extent of a RA participant's functional ability. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week (at each specified visit) rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, and ranged from 0 to 3, where 0 = no disability and 3 = completely disabled, higher score indicated more disability. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
Week 4Week 12Week 24
Sarilumab-0.2-0.4-0.5

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Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Week 24

RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological well-being, • sleep disturbance, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status. (NCT03449758)
Timeframe: Baseline, Week 24

Interventionscore on a scale (Mean)
Sarilumab-2.4

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Change From Baseline in Clinical Disease Activity Index Total Score at Weeks 4, 12, and 24

CDAI was a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment of disease (in cm). CDAI total score ranges from 0 to 76 with a lower score indicating less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
Week 4Week 12Week 24
Sarilumab-9.8-12.2-14.6

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Change From Baseline in Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24

DAS28-ESR was a composite score that included 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score <= 3.2 indicated LDA, > 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
Week 4Week 12Week 24
Sarilumab-1.8-2.3-2.7

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Change From Baseline in Duration of Morning Stiffness at Weeks 4, 12, and 24

Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. At each specified time point, duration of morning stiffness was reported by the participant during the visit. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionminutes (Mean)
Week 4Week 12Week 24
Sarilumab-39.9-47.9-52.8

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Number of Participants Achieving Clinical Disease Activity Index: Low Disease Activity (CDAI Score <=10.0) and Remission (CDAI Score <=2.8) Weeks 12, and 24

CDAI was a composite index constructed to measure clinical remission in RA that does not included a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment (in cm). Total score ranged from 0 to 76 with a lower score indicated less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA. (NCT03449758)
Timeframe: Weeks 12 and 24

InterventionParticipants (Count of Participants)
LDA: Week 12LDA: Week 24Remission: Week 12Remission: Week 24
Sarilumab29291820

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Change From Baseline in Erythrocyte Sedimentation Rate at Weeks 4, 12, and 24

ESR was a laboratory test to provide non-specific measure of inflammation in the body. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/h. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionmm/h (Mean)
Week 4Week 12Week 24
Sarilumab-18.1-19.5-22.0

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Number of Tender Joints at Baseline, Weeks 4, 12, and 24

Number of joints with tenderness are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionjoints (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab7.34.73.52.5

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Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Total Scores at Weeks 4, 12 and 24

FACIT-F was a 13-item questionnaire that assess fatigue in participants under chronic illness therapy. Participants scored each item on a 5-point Likert scale ranged from 0 to 4 (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The scores of each item were reversed during score calculations, so that higher score values indicated more favorable conditions. Total score was the sum of score from each item and resulted in a score range from 0 to 52, with higher score indicated better participant health status (lower level of fatigue). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
Week 4Week 12Week 24
Sarilumab-4.8-6.4-7.6

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Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety (HADS-A) and Depression (HADS-D) Subscale Scores at Weeks 4, 12 and 24

HADS questionnaire measures the presence and severity of anxiety and depression in both hospital and community settings. The questionnaire comprised of 14 items divided into 2 subscales: 7 items for anxiety subscale (HADS-A) and 7 items for depression subscale (HADS-D). Each item was scored on a 0 to 3 rating scale. The anxiety and depression subscales each ranged from 0 to 21 (0-7: normal, 8-10: borderline abnormal and 11-21: abnormal), where higher scores indicated greater severity of anxiety/depression. The subscales were independent for each result of depression and anxiety. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
HADS-A: Week 4HADS-A: Week 12HADS-A: Week 24HADS-D: Week 4HADS-D: Week 12HADS-D: Week 24
Sarilumab-1.0-2.1-1.9-0.4-1.2-1.7

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Change From Baseline in International Physical Activity Questionnaire Total Score at Weeks 4, 12 and 24

IPAQ was a 27-item self-reported questionnaire designed to measure physical activity of participant. The score was reported in MET minutes per week. MET minutes represented the amount of energy expended to carry out physical activity. For IPAQ total score, the minimum value is zero and there is no maximum. Higher scores mean better levels of physical activity. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

InterventionMET minutes per week (Mean)
Week 4Week 12Week 24
Sarilumab175.6533.4382.0

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Change From Baseline in Multidimensional Assessment of Thymic States Scale Total Score at Weeks 4, 12 and 24

MAThyS was a multi-dimensional self-administered questionnaire comprised of five dimensions (emotional reactivity, cognition speed, psychomotor function, motivation and sensory perception) divided into 20 items relating to individual states as perceived by participants for the preceding week (at each specified Week). Each item was measured on a VAS (in cm) ranging from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state). Total MAThyS score was sum of the 20 items and that might vary from score range 0 to 200 with lower scores indicated general inhibition and higher scores indicated general excitation. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventioncm (Mean)
Week 4Week 12Week 24
Sarilumab-0.22.9-1.1

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Change From Baseline in Number of Swelling Joints at Weeks 4, 12, and 24

Number of joints with swelling are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionjoints (Mean)
Week 4Week 12Week 24
Sarilumab-3.9-4.1-4.7

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Change From Baseline in Number of Tender Joints at Weeks 4, 12, and 24

Number of joints with tenderness are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionjoints (Mean)
Week 4Week 12Week 24
Sarilumab-2.5-3.7-4.8

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Change From Baseline in Patient Global Assessment of Disease Activity Score by Visual Analog Scale at Weeks 4, 12, and 24

PtGA of disease activity was measured using a 100 mm horizontal VAS ranged from 0=no pain to 100=maximum pain imaginable, where higher score indicated more disease activity. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionmm (Mean)
Week 4Week 12Week 24
Sarilumab-17.2-24.3-26.7

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Change From Baseline in Rheumatoid Arthritis Impact of Disease Total Score at Weeks 4 and 12

RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological wellbeing, • sleep disturbance, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status. (NCT03449758)
Timeframe: Baseline, Weeks 4 and 12

Interventionscore on a scale (Mean)
Week 4Week 12
Sarilumab-1.2-1.8

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Disease Activity Score-28 for Rheumatoid Arthritis With Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline, Weeks 4, 12, and 24

DAS28-ESR was a composite score that included 4 variables: tender joint count (TJC) (based on 28 joints); swollen joint count (SJC) (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score less than or equal to (<=) 3.2 indicated low disease activity (LDA), greater than (>) 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab5.03.12.62.3

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Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 4, 12 and 24

HAQ-DI was a participant-oriented questionnaire developed specifically to assess the extent of a RA participant's functional ability. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week (at each specified visit) rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, and ranged from 0 to 3, where 0 = no disability and 3 = completely disabled, higher score indicated more disability. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab1.31.10.80.8

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Rheumatoid Arthritis Impact of Disease Total Score at Baseline, Weeks 4, 12 and 24

RAID was a participant reported outcome measure used to evaluate the impact of RA on participant's quality of life which comprised 7 domains: • pain, • function, • fatigue, • physical and psychological well-being, • sleep disturbances, and • coping. Each domain was a single question scored on a 0 to 10 continuous NRS. The values for each of these domains were weighed by participant assessment of relative importance and combined in a single value. Total RAID score range was 0 (not affected, very good) to 10 (most affected), where higher value indicated worse status. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
Week 4Week 12Week 24
Sarilumab4.63.93.3

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Patient Global Assessment (PtGA) of Disease Activity Score by Visual Analog Scale (VAS) at Baseline, Weeks 4, 12 and 24

PtGA of disease activity was measured using a 100 millimeters (mm) horizontal VAS ranged from 0=no pain to 100=maximum pain imaginable, where higher score indicated more disease activity. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionmm (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab61.144.136.634.6

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Clinical Disease Activity Index (CDAI) Total Score at Baseline, Weeks 4, 12, and 24

CDAI was a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global disease activity (in cm), and physician's global assessment of disease (in cm). CDAI total score ranges from 0 to 76 with a lower score indicating less disease activity. A CDAI score of <=2.8 represents clinical remission and a score of <=10.0 represents LDA. (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionscore on a scale (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab22.512.69.98.1

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Number of Swollen Joints at Baseline, Weeks 4, 12, and 24

Number of joints with swelling are reported. Joints which were assessed included 28 joints (which included shoulders, elbows, wrists, knees and 2 joints in each finger and thumb). (NCT03449758)
Timeframe: Baseline, Weeks 4, 12 and 24

Interventionjoints (Mean)
BaselineWeek 4Week 12Week 24
Sarilumab6.32.51.91.6

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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the study treatment. SAE: Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that occurred in the time from the first injection of study drug up to 39.7 weeks. (NCT03449758)
Timeframe: Baseline up to end of study (up to 39.7 weeks)

InterventionParticipants (Count of Participants)
SAETEAEAE leading to death
Sarilumab10760

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Number of Participants Achieving Low Disease Activity (DAS28 ESR Score <=3.2) and Remission (DAS28 ESR Score <2.6) at Weeks 12, and 24

DAS28-ESR was a composite score that included 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable) marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score ranged from 0-10, higher score indicated more disease activity. The DAS28-ESR score provided a number indicating the current disease activity of the RA. A DAS28-ESR score above 5.1 indicated high disease activity, DAS28-ESR score <= 3.2 indicated LDA, > 3.2 to <=5.1 implied moderate disease activity and DAS28-ESR score below 2.6 indicated disease remission. (NCT03449758)
Timeframe: Weeks 12 and 24

InterventionParticipants (Count of Participants)
LDA: Week 12LDA: Week 24Remission: Week 12Remission: Week 24
Sarilumab1244045

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Number of Participants Who Are Eligible, Consent, and Complete the 48 Weeks Study

To establish acceptability of this treatment approach assessing proportion of patients who are eligible, consent and complete the 48 week study. We will examine how many patients in the MONITOR cohort are eligible per year. All eligible patients in the MONITOR cohort will be approached and invited to join the study. We will then review how many patients complete the 48 week study period attending all visits from baseline to 48 weeks (0, 12, 24, 36 and 48). (NCT03797872)
Timeframe: 48 weeks

InterventionParticipants (Count of Participants)
Standard Care0

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Overall Response Rate

Defined as the proportion of patients with a documented response (complete response [CR] or partial [PR]) any time during study treatment. Response will be categorized by modified severity weighted assessment tool (mSWAT). Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals. The treatment response was assessed after each 28-day cycle treatment. (NCT04463615)
Timeframe: Up to 42 days from the start time of the initial study treatment. Patient received one 28-day cycle treatment and then was off treatment on Day 14 of the second cycle due to disease progression.

Interventionpercentage of participants (Number)
Treatment (Leflunomide)0

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Complete Response Rate

Defined as the proportion of patients with a documented CR any time during study treatment. Response will be assessed by mSWAT. Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals. The treatment response was assessed after each 28-day cycle treatment. (NCT04463615)
Timeframe: Up to 42 days from the start time of the initial study treatment. Patient received one 28-day cycle treatment and was off treatment on Day 14 of the second cycle due to disease progression.

Interventionpercentage of participants (Number)
Treatment (Leflunomide)0

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