Page last updated: 2024-11-08

dimethyl fumarate

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Cross-References

ID SourceID
PubMed CID637568
CHEMBL ID2107333
CHEBI ID76004
SCHEMBL ID41835
SCHEMBL ID41836
MeSH IDM0157348

Synonyms (141)

Synonym
bg 00012
bg00012
bg 12 compound
fag 201
fag201
dimethylfumarate
tecfidera
2-butenedioic acid, (2e)-, dimethyl ester
dimethyl fumarate [usan]
4-02-00-02205 (beilstein handbook reference)
fo2303mni2 ,
bg 12 [fumarate]
2-butenedioic acid (2e)-, 1,4-dimethyl ester
azl o 211089
unii-fo2303mni2
bg-12 [fumarate]
hsdb 7725
dimethylester kyseliny fumarove
LS-13141
HY-17363
BRD-K31111078-001-01-8
nsc25942
nsc-25942
2-butenedioic acid, dimethyl ester, (e)-
brn 0774590
einecs 210-849-0
ai3-07872
nsc 25942
2-butenedioic acid, dimethyl ester
fumaderm
nsc 167432
2-butenedioic acid (2e)-, dimethyl ester
dimethyl 2-butenedioate
ethylene, 1,2-bis(methoxycarbonyl)-, trans-
tl 353
dimethylester kyseliny fumarove [czech]
tecfidera (tn)
dimethyl fumarate (jan/usan)
D03846
dimethyl (e)-but-2-enedioate
2-butenedioic acid, dimethyl ester, (2e)-
dimethyl (2e)-2-butenedioate
allomaleic acid dimethyl ester
nsc-167432
624-49-7
ethylene,2-bis(methoxycarbonyl)-, trans-
2-butenedioic acid (e)-, dimethyl ester
dimethyl fumarate ,
methyl fumarate
trans-1,2-ethylenedicarboxylic acid dimethyl ester
fumaric acid dimethyl ester
wln: 1ov1u1vo1 -t
fumaric acid, dimethyl ester
dimethyl trans-ethylenedicarboxylate
trans-butenedioic acid dimethyl ester
nsc167432
boletic acid dimethyl ester
dimethyl fumarate, 97%
STK039379
dimethyl (2e)-but-2-enedioate
bg-00012
panaclar
azl-o-211089
fag-201
bg-12
F0069
AKOS000121333
23055-10-9
HMS3264D14
(e)-but-2-enedioic acid dimethyl ester
pharmakon1600-01506154
nsc760139
nsc-760139
dimethyl fumar
las41008
azl 0 211089
fp187
las-41008
bg 12
fp-187
azl-0211089
chebi:76004 ,
CHEMBL2107333
bis-methyl ester
dimethyl fumarate [who-dd]
dimethyl fumarate [orange book]
dimethyl fumarate [jan]
dimethyl fumarate [vandf]
dimethyl fumarate [hsdb]
dimethyl fumarate [mi]
CS-0909
S2586
1,2-bis(methoxycarbonyl)-trans-ethylene
gtpl7045
CCG-213618
SCHEMBL41835
SCHEMBL41836
1,4-dimethyl but-2-enedioate
DTXSID4060787
2(e)-butenedioic acid 1,4-dimethyl ester
(e)-dimethyl fumarate
but-2-enedioic acid, dimethyl ester
AB00172980_03
AB00172980_04
F0001-1675
fumarate, dimethyl
SR-01000944222-1
sr-01000944222
dimethyl fumarate, certified reference material, tracecert(r)
bdbm50504654
H11241
dimethyl fumarate, vetec(tm) reagent grade, 97%
fumaric acid-dimethyl ester
Z49500377
(e)-ch3oc(o)ch=chc(o)och3
dimethyl ester(e)-2-butenedioic acid
dimethyl ester(2e)-2-butenedioic acid
dimethyl fumarate (usan)
fumaric acid, dimethyl ester (8ci)
trans-1, 2-ethylenedicarboxylic acid dimethyl ester
SW219154-1
DB08908
Q418123
dimethyl trans-butenedioate
12287-98-8
fumaric acid-dimethyl ester 1000 microg/ml in acetonitrile
dimethyl (~{e})-but-2-enedioate
eou ,
dimethyl-fumarate
but-2-enedioic aciddimethyl ester
CS-0369103
(e/z)-dimethyl fumarate
EN300-16090
1,4-dimethyl (2e)-but-2-enedioate
EN300-305306
dimethyl (e)-butenedionate
(e)-2-butenedioic acid, dimethyl ester
bg-12 (fumarate)
dimethyl (e)-butenedioate
bg 12 (fumarate)
2-butenedioic acid, dimethylester

Research Excerpts

Overview

Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS) It is a fumaric acid ester used in the treatment of psoriasis. Its mechanism of action is unclear, it possesses anti-inflammatory and anti-oxidant properties and also impacts on cell metabolism.

ExcerptReferenceRelevance
"Dimethyl fumarate (DMF) is an oral MS medication with unknown mechanism of action."( Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients.
Baharnoori, M; Chitnis, T; Gonzalez, CT; Healy, BC; Keyhanian, K; Saxena, S; Sotiropoulos, MG; Wilson, R, 2021
)
1.6
"Dimethyl fumarate is an efficient therapy used widely in patients with relapsing-remitting multiple sclerosis (RRMS). "( Immunological effects of dimethyl fumarate treatment in blood and CSF of patients with primary progressive MS.
Holm Hansen, R; Højsgaard Chow, H; Sellebjerg, F; Talbot, J; von Essen, MR, 2021
)
2.37
"Dimethyl fumarate (DMF) is an oral disease-modifying drug for MS in adults with relatively stable disease; however, its use in young children has not been heavily documented in the current literature."( Successful treatment with dimethyl fumarate in a child with relapsing-remitting multiple sclerosis.
Abe, Y; Endo, W; Numata-Uematsu, Y; Oikawa, Y; Okubo, Y; Saijo, N; Takahashi, T; Uematsu, M, 2022
)
1.74
"Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). "( Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate.
Balusha, A; Berger, W; Casserly, C; Chu, L; Morrow, SA, 2022
)
2.38
"Dimethyl fumarate (DMF) is a fumaric acid ester used in the treatment of psoriasis and relapsing remitting multiple sclerosis and, while its mechanism of action is unclear, it possesses anti-inflammatory and anti-oxidant properties and also impacts on cell metabolism."( The Modulatory Effects of DMF on Microglia in Aged Mice Are Sex-Specific.
Bechet, S; Lynch, MA; Mela, V; O'Neill, E; Sayd Gaban, A; Walsh, A, 2022
)
1.44
"Dimethyl fumarate (DMF) is a drug currently in use in oral therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS) due to its immunomodulatory and neuroprotective effects. "( Effects Mediated by Dimethyl Fumarate on In Vitro Oligodendrocytes: Implications in Multiple Sclerosis.
Di Marino, T; Guerriero, C; Puliatti, G; Tata, AM, 2022
)
2.49
"Dimethyl fumarate (DMF) is an antioxidative and anti-inflammatory drug approved for treatment of multiple sclerosis and psoriasis; however, beneficial effects of DMF have also been found in other inflammatory diseases and cancers. "( Dimethyl fumarate: A review of preclinical efficacy in models of neurodegenerative diseases.
Majkutewicz, I, 2022
)
3.61
"Dimethyl fumarate (DMF) is a fumaric acid derivative clinically approved for the treatment of some inflammatory diseases, but the underlying mechanism for its therapeutic effects remains incompletely understood. "( Dimethyl fumarate ameliorates autoimmune hepatitis in mice by blocking NLRP3 inflammasome activation.
Chen, SY; He, XH; Hu, B; Huang, XD; Liang, QQ; Liu, SY; Luo, SQ; Ni, ST; Ouyang, DY; Qiu, JH; Shi, FL; Xu, R; Zeng, B; Zha, QB, 2022
)
3.61
"Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear."( Dimethyl fumarate improves cognitive impairment by enhancing hippocampal brain-derived neurotrophic factor levels in hypothyroid rats.
Pan, H; Wang, X; Wang, Y; Yan, C, 2022
)
3.61
"Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS). "( High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis.
Becher, B; Benkert, P; Callegari, I; Cichon, S; Claassen, M; Derfuss, T; Diebold, M; Galli, E; Gonzalo Núñez, N; Herms, S; Ingelfinger, F; Kappos, L; Kopf, A; Kuhle, J; Sanderson, NSR, 2022
)
2.4
"Dimethyl fumarate (DMF) is an effective treatment for relapsing remitting Multiple Sclerosis (MS) and its mechanisms of action encompass immunomodulatory and cytoprotective effects. "( Evidence for novel cell defense mechanisms sustained by dimethyl fumarate in multiple sclerosis patients: the HuR/SOD2 cascade.
Bergamaschi, R; Boschi, F; Campagnoli, LIM; Fahmideh, F; Fusco, S; Govoni, S; Mallucci, G; Marchesi, N; Pascale, A; Tavazzi, E, 2022
)
2.41
"Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS."( Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.
Aladro-Benito, Y; Álvarez-Lafuente, R; Fernández-Miranda, I; García-Hernández, R; García-Merino, A; la Fuente, OR; Posada-Ayala, M; Romero, J; Royuela, A; Sabín-Muñoz, J; Sánchez-López, AJ; Sánchez-Sanz, A, 2022
)
1.66
"Dimethyl fumarate (DMF) is a first-line prodrug for the treatment of relapsing-remitting multiple sclerosis (RRMS) that is completely metabolized to monomethyl fumarate (MMF), the active metabolite, before reaching the systemic circulation. "( Alcohol inhibits the metabolism of dimethyl fumarate to the active metabolite responsible for decreasing relapse frequency in the treatment of multiple sclerosis.
Laizure, SC; Meibohm, B; Parker, RB; Srivastava, A; Temrikar, ZH; Yang, B, 2022
)
2.44
"Dimethyl fumarate (DMF) is a small molecule currently approved and used in the treatment of psoriasis and multiple sclerosis due to its immuno-modulatory, anti-inflammatory, and antioxidant properties. "( The Challenge of Dimethyl Fumarate Repurposing in Eye Pathologies.
Amadio, M; Govoni, S; Manai, F, 2022
)
2.5
"Dimethyl fumarate (DMF) is an immune-modulating drug used in the treatment of multiple sclerosis and psoriasis shows antioxidant, anti-inflammatory, and antifibrotic effects."( Dimethyl fumarate attenuates paraquat-induced pulmonary oxidative stress, inflammation and fibrosis in mice.
Kalantar, H; Khodayar, MJ; Mahmoudi, Z; Mansouri, E; Mohammadi, E, 2023
)
3.07
"Dimethyl fumarate (DMF) is a frequently prescribed oral DMT medication worldwide."( Medication adherence and health outcomes in persons with multiple sclerosis treated with dimethyl fumarate.
Brecl Jakob, G; Jožef, M; Kos, M; Locatelli, I; Rot, U, 2023
)
1.85
"Dimethyl fumarate (DMF) is a first-line oral therapy for relapsing-remitting multiple sclerosis (RRMS). "( Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.
Baeva, ME; Camara-Lemarroy, CR; Greenfield, J; Metz, LM, 2023
)
2.56
"Dimethyl fumarate (DMF) is an immunomodulatory drug currently approved for the treatment of multiple sclerosis and psoriasis. "( Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke.
Bayat, M; Borhani-Haghighi, A; Hooshmandi, E; Karimi, F; Karimlou, S; Mallahzadeh, A; Nabavizadeh, SA; Namavar, MR; Owjfard, M; Saadi, MI; Salehi, MS; Zafarmand, SS, 2023
)
2.61
"Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has been approved for treating multiple sclerosis (MS) and psoriasis due to anti-inflammatory effect. "( Dimethyl fumarate possesses antiplatelet and antithrombotic properties.
Chu, X; Geng, C; Gui, X; Ju, W; Li, Y; Li, Z; Qiao, J; Sun, Y; Wang, X; Xu, K; Xu, M; Yuan, K; Zeng, L; Zhang, J, 2023
)
3.8
"Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. "( Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders.
Amadio, M; Arfini, D; Comincini, S; Gjyzeli, A; Manai, F; Micco, SG; Zanoletti, L, 2023
)
3.8
"Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). "( Dimethyl fumarate-related immune and transcriptional signature is associated with clinical response in multiple sclerosis-treated patients.
Al-Shahrour, F; Brea-Álvarez, B; Elvira, V; García-Grande, A; García-Hernández, R; García-Martín, S; García-Merino, A; Moreno-Torres, I; Ramil, E; Rodríguez-De la Fuente, O; Sabín-Muñoz, J; Sánchez-López, AJ; Sánchez-Sanz, A, 2023
)
3.8
"Dimethyl fumarate (DMF) is an orally accessible methyl ester of fumaric acid with putative neuroprotective and immunomodulatory properties."( An RNAi-Mediated Reduction in Transcription Factor Nrf-2 Blocks the Positive Effects of Dimethyl Fumarate on Metabolic Stress in Alzheimer's Disease.
Basilotta, R; Bulzomì, M; Casili, G; Cuzzocrea, S; Esposito, E; Lanza, M; Oddo, S, 2023
)
1.85
"Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable."( Dimethyl fumarate modulates the dystrophic disease program following short-term treatment.
Apostolopoulos, V; Arthur, PG; Bagaric, RM; Bautista, AP; Campelj, DG; Dargahi, N; de Haan, JB; Debrincat, D; Debruin, DA; Fischer, D; Guven, N; Hafner, P; Kourakis, S; Pompeani, N; Ritenis, EJ; Rybalka, E; Sahakian, L; Stupka, N; Terrill, JR; Timpani, CA, 2023
)
3.07
"Dimethyl fumarate (DMF) is a Food and Drug Administration-approved antioxidant and anti-inflammatory agent."( Dimethyl Fumarate Ameliorated Cardiorenal Anemia Syndrome and Improved Overall Survival in Dahl/Salt-Sensitive Rats.
Arai, Y; Ito, S; Manabe, E; Tsujino, T; Yamatani, F, 2023
)
3.07
"Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. "( New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo.
Bernal, M; Cárdenas, C; Caro, C; DeBerardinis, RJ; Domínguez, A; García-Martín, ML; Martínez-Poveda, B; Medina, MÁ; Ocaña, MC; Quesada, AR; Vu, HS; Yang, C, 2023
)
2.62
"Dimethyl fumarate (DMF) is a disease-modifying therapy for patients with relapsing-remitting multiple sclerosis (RRMS). "( Dimethyl fumarate therapy reduces memory T cells and the CNS migration potential in patients with multiple sclerosis.
Christensen, JR; Holm Hansen, R; Højsgaard Chow, H; Sellebjerg, F; von Essen, MR, 2020
)
3.44
"Dimethyl fumarate (DMF) is an oral drug approved by the FDA for relapsing MS with unique immunomodulatory and cytoprotective effects."( An evaluation of dimethyl fumarate for the treatment of relapsing remitting multiple sclerosis.
Carter, JL; Valencia-Sanchez, C, 2020
)
1.62
"Dimethyl fumarate (DMF) is a potent activator of Nrf2 and has been shown to inhibit osteoclastogenesis."( Dimethyl fumarate prevents osteoclastogenesis by decreasing NFATc1 expression, inhibiting of erk and p38 MAPK phosphorylation, and suppressing of HMGB1 release.
Kawamoto, M; Nishioku, T; Okamoto, K; Okizono, R; Sakai, E; Tsukuba, T, 2020
)
2.72
"Dimethyl fumarate (DMF) is a fumaric acid diester which is used for the treatment of psoriasis and multiple sclerosis."( Dimethyl fumarate protects cardiomyocytes against oxygen-glucose deprivation/reperfusion (OGD/R)-induced inflammatory response and damages via inhibition of Egr-1.
Cheng, Z; Ding, Z; Quan, X; Xie, Z; Zhang, L; Zhao, J, 2020
)
2.72
"Dimethyl fumarate (DMF) is an approved anti-inflammatory drug already in clinical use for psoriasis and multiple sclerosis."( Dimethyl fumarate suppresses metastasis and growth of melanoma cells by inhibiting the nuclear translocation of NF-κB.
Asano, R; Imano, M; Itoh, T; Nishida, S; Satou, T; Takeda, T; Tsubaki, M, 2020
)
2.72
"Dimethyl fumarate (DMF) is a first line medication for multiple sclerosis. "( Dimethyl fumarate induced lymphopenia in multiple sclerosis: A review of the literature.
Dello Russo, C; Pirmohamed, M; Scott, KA, 2021
)
3.51
"Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an antioxidant and anti-inflammatory agent."( Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice.
Brito-Gitirana, L; Cattani-Cavalieri, I; da Maia Valença, H; Moraes, JA; Romana-Souza, B; Schmidt, M; Valença, SS, 2020
)
2.72
"Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. "( Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis.
Buscarinu, MC; Centonze, D; Conte, A; Cortese, A; Elia, G; Fantozzi, R; Ferraro, E; Gasperini, C; Ianniello, A; Landi, D; Lucchini, M; Marfia, GA; Mirabella, M; Nociti, V; Pozzilli, C; Prosperini, L; Salvetti, M; Tortorella, C, 2021
)
2.32
"Dimethyl fumarate (DMF) is a treatment for moderate-to-severe psoriasis and multiple sclerosis. "( Oral dimethyl fumarate induces changes within the peripheral neutrophil compartment of patients with psoriasis that are linked with skin improvement.
Gerdes, S; Morrison, PJ; Mrowietz, U; Suhrkamp, I, 2021
)
2.58
"Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. "( A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles.
Galindo, MF; García-Fernández, AE; García-Fernández, FJ; Ikuta, I; Jordan, J; Nava, E; Solis García Del Pozo, J, 2021
)
2.32
"Dimethyl fumarate is a medication approved for the treatment of relapsing-remitting multiple sclerosis. "( Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis.
Boullosa-Lale, S; Crespo-Diz, C; González-Freire, L; Martínez-Martínez, L, 2020
)
2.3
"Dimethyl fumarate (DMF) is a drug used for the treatment of multiple sclerosis and has shown a neuroprotective effect against other neurodegenerative diseases."( Dimethyl fumarate abridged tauo-/amyloidopathy in a D-Galactose/ovariectomy-induced Alzheimer's-like disease: Modulation of AMPK/SIRT-1, AKT/CREB/BDNF, AKT/GSK-3β, adiponectin/Adipo1R, and NF-κB/IL-1β/ROS trajectories.
Abd El-Fatah, IM; Abdallah, DM; Abdelrazek, HMA; El-Abhar, HS; Ibrahim, SM, 2021
)
2.79
"Dimethyl Fumarate is a disease-modifying medication used to treat RRMS patients that can induce lymphopenia."( Cross-sectional analysis of peripheral blood mononuclear cells in lymphopenic and non-lymphopenic relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.
Barilla, D; Blevins, G; Giuliani, F; Jiang, B; Lee, CH; Nakhaei-Nejad, M, 2021
)
1.54
"Dimethyl fumarate (DMF) is a fumaric acid esters derivate approved for plaque psoriasis as first-line systemic therapy. "( Dimethyl fumarate treatment for psoriasis in a real-life setting: A multicentric retrospective study.
Arginelli, F; Bardazzi, F; Borghi, A; Conti, A; Corazza, M; Di Lernia, V; Di Nuzzo, S; Filippi, F; Monti, A; Morotti, C; Motolese, A; Odorici, G; Valpiani, G, 2021
)
3.51
"Dimethyl fumarate (DMF) is a novel antioxidant that selectively reduces hydroxyl radicals. "( Activation of Nrf2 Pathway by Dimethyl Fumarate Attenuates Renal Ischemia-Reperfusion Injury.
Jindong, L; Sudong, L; Wei, G; Wei, J; Wei, Z; Yang, Z; Yashi, R; Zhen, X, 2021
)
2.35
"Dimethyl fumarate (DMF) is an anti-inflammatory drug that exerts its effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway."( Dimethyl fumarate prevents cytotoxicity and apoptosis mediated by oxidative stress in human adipose-derived mesenchymal stem cells.
Bahadori, MH; Roudkenar, MH; Roushandeh, AM; Shekarchi, S, 2021
)
2.79
"Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action."( Mechanism of action of three newly registered drugs for multiple sclerosis treatment.
Cudnoch-Jędrzejewska, A; Członkowski, A; Kasarełło, K; Mirowska-Guzel, D, 2017
)
1.18
"Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS)."( Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case-control study protocol for dimethyl fumarate-induced lymphopenia.
Bernatsky, S; Carleton, B; Carruthers, R; Kingwell, E; Kowalec, K; Marrie, RA; Ross, CJD; Traboulsee, A; Tremlett, H, 2017
)
1.37
"Dimethyl fumarate (DMF) is an orally administered drug with neuroprotective and immunomodulatory activities. "( Transdermal delivery of dimethyl fumarate for Alzheimer's disease: Effect of penetration enhancers.
Ameen, D; Michniak-Kohn, B, 2017
)
2.2
"Dimethyl fumarate (DMF) is an immunomodulatory compound to treat multiple sclerosis and psoriasis with neuroprotective potential. "( Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection.
Griemert, E; Grob, T; Hirnet, T; Krämer, T; Menzel, L; Methner, A; Radyushkin, K; Schaefer, MKE; Thal, SC, 2017
)
3.34
"Dimethyl fumarate is a frequent prescription for the management of numerous neurological disorders. "( Stearic acid based, systematically designed oral lipid nanoparticles for enhanced brain delivery of dimethyl fumarate.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
2.11
"Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. "( Donor variability may mask dimethyl fumarate's effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells.
Fiedler, SE; Kerns, AR; Love, HN; Salinthone, S; Tsang, C, 2017
)
2.19
"Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2)."( Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats.
Barichello, T; Bonfante, S; Cardoso, T; Danielski, LG; De Carli, RJ; de Oliveira, AN; Fileti, ME; Garbossa, L; Giustina, AD; Goldim, MP; Mathias, K; Petronilho, F; Zarbato, GF, 2018
)
2.64
"Dimethyl fumarate (DMF) is a new oral option for disease-modifying therapy (DMT) in patients with remitting multiple sclerosis as a first line treatment. "( [Dimethyl fumarate (tecfidera) is the first line treatment choice in patients with remitting multiple sclerosis].
Shmidt, TE,
)
2.48
"Dimethyl fumarate (DMF) is an oral treatment for relapsing-remitting multiple sclerosis (MS) with anti-inflammatory and possible neuroprotective properties. "( Effect of dimethyl fumarate on gray and white matter pathology in subjects with relapsing multiple sclerosis: a longitudinal study.
Bergsland, N; Hagemeier, J; Tavazzi, E; Weinstock-Guttman, B; Zivadinov, R, 2018
)
2.33
"Dimethyl fumarate (DMF) is a promising agent for MS treatment, although it is associated with concerns such as poor brain permeation, multiple dosing, and gastrointestinal flushing."( Preclinical Explorative Assessment of Dimethyl Fumarate-Based Biocompatible Nanolipoidal Carriers for the Management of Multiple Sclerosis.
Gupta, V; Kaur, R; Kaushal, N; Kumar, A; Kumar, P; Malik, R; Raza, K; Sharma, G; Thakur, K, 2018
)
1.47
"Dimethyl fumarate is an FDA-approved oral immunomodulatory drug with anti-inflammatory properties that induces the upregulation of the anti-oxidant transcription factor, nuclear factor erythroid-derived factor 2. "( Effect of dimethyl fumarate on renal disease progression in a genetic ortholog of nephronophthisis.
Luciuk, M; Mannix, C; Oey, O; Rangan, G; Rao, P; Rogers, NM; Sagar, P; Wong, A, 2018
)
2.33
"Dimethyl fumarate is a potential treatment for pediatric multiple sclerosis."( Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS).
Alroughani, R; Das, R; Eraly, S; Penner, N; Pultz, J; Taylor, C, 2018
)
1.47
"Dimethyl fumarate (DMF) is an important agent against inflammatory response and reactive species in CNS disorders."( Dimethyl Fumarate Limits Neuroinflammation and Oxidative Stress and Improves Cognitive Impairment After Polymicrobial Sepsis.
Barichello, T; da Rosa, N; Danielski, LG; de Oliveira Junior, AN; de Souza Goldim, MP; Florentino, D; Fortunato, JJ; Giustina, AD; Gomes, ML; Laurentino, AO; Mathias, K; Moreira, AP; Petronilho, F; Schuck, PF; Steckert, AV; Trombetta, T; Zarbato, GF, 2018
)
2.64
"Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood."( Relapsing-Remitting Multiple Sclerosis Is Characterized by a T Follicular Cell Pro-Inflammatory Shift, Reverted by Dimethyl Fumarate Treatment.
Andreu, V; Calles, C; Clemente, A; Cunill, V; Díaz, RM; Ferrer, JM; Jiménez, MLR; López-Gómez, A; Massot, M; Núñez, V; Pons, J; Vives-Bauzà, C, 2018
)
1.41
"Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis."( Dimethyl fumarate accelerates wound healing under diabetic condition.
Jiang, Z; Li, H; Li, Y; Ma, F; Song, Y; Wu, H; Zhang, H, 2018
)
2.64
"Dimethyl fumarate (DMF) is a new oral drug for the treatment of multiple sclerosis, and has neuroprotective effects via up-regulation of the nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response."( Dimethyl fumarate ameliorates chemotherapy agent-induced neurotoxicity in vitro.
Kawashiri, T; Kobayashi, D; Miyagi, A; Shigematsu, N; Shimazoe, T; Shimizu, S, 2018
)
2.64
"Dimethyl fumarate (DMF) is a disease-modifying therapy used for patients with relapsing-remitting multiple sclerosis (RRMS). "( Dimethyl fumarate therapy suppresses B cell responses and follicular helper T cells in relapsing-remitting multiple sclerosis.
Holm Hansen, R; Højsgaard Chow, H; Rode von Essen, M; Sellebjerg, F, 2019
)
3.4
"Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. "( Dimethyl fumarate-associated transient bone marrow oedema syndrome.
Kermode, A; Prince, R; Triplett, J; Vijayan, S, 2019
)
3.4
"Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. "( Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis.
Anvari, E; Baradaran, B; Ghalamfarsa, G; Hojjat-Farsangi, M; Hosseini, A; Jadidi-Niaragh, F; Masjedi, A, 2019
)
3.4
"Dimethyl fumarate (DMF) is a potent activator of (Nrf-2), its anti-inflammatory and antioxidant properties of DMF have been highlighted recently."( Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway.
Abdel-Rahman, N; Abdelrahman, RS, 2019
)
2.68
"Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). "( Dimethyl fumarate, a two-edged drug: Current status and future directions.
Alexandre, J; Batteux, F; Jacob, C; Kavian, N; Leroy, K; Nicco, C; Saidu, NEB, 2019
)
3.4
"Dimethyl fumarate (DMF) is an oral, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis (RRMS). "( Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis.
Dhib-Jalbut, S; Ito, K; Soin, D; Yadav, SK, 2019
)
2.22
"Dimethyl fumarate (DMF) is a prescribed treatment for multiple sclerosis and has also been used to treat psoriasis. "( Dimethyl Fumarate Disrupts Human Innate Immune Signaling by Targeting the IRAK4-MyD88 Complex.
Blewett, MM; Casanova, JL; Cravatt, BF; de la Torre, JC; Lazar, DC; Studer, S; Suciu, RM; Takaya, J; Teijaro, JR; Vinogradova, EV; Zaro, BW, 2019
)
3.4
"Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress."( Dimethyl Fumarate Attenuates Oxaliplatin-Induced Peripheral Neuropathy without Affecting the Anti-tumor Activity of Oxaliplatin in Rodents.
Kawashiri, T; Kobayashi, D; Miyagi, A; Shigematsu, N; Shimazoe, T; Shimizu, S, 2019
)
2.68
"Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). "( Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes.
Aeinehband, S; Al Nimer, F; Badam, TVS; Carlström, KE; Checa, A; Enoksson, SL; Ewing, E; Gomez-Cabrero, D; Granqvist, M; Gustafsson, M; Gyllenberg, A; Huang, J; Jagodic, M; Kockum, I; Olsson, T; Piehl, F; Wheelock, CE, 2019
)
2.26
"Dimethyl fumarate (DMF) is an effective inhibitor of mold growth. "( Footwear contact dermatitis from dimethyl fumarate.
Doležalová, A; Šimaljakova, M; Švecová, D, 2013
)
2.11
"Dimethyl fumarate is a new footwear allergen and was responsible for severe ACD in our patients. "( Footwear contact dermatitis from dimethyl fumarate.
Doležalová, A; Šimaljakova, M; Švecová, D, 2013
)
2.11
"Dimethyl fumarate (DMF) is an orally administered agent that has been used for over 40 years for the treatment of psoriasis. "( BG-12 in multiple sclerosis.
Fox, RJ; Phillips, JT, 2013
)
1.83
"Dimethyl fumarate is an orally available treatment option for relapsing-remitting multiple sclerosis (MS) in a new formulation with improved gastroenteric coating. "( Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects.
Gold, R; Linker, RA, 2013
)
3.28
"Dimethyl fumarate (DMF) is a recently approved first-line therapy for multiple sclerosis."( Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α).
Chen, Y; Fang, J; Gao, K; Li, H; Liu, Y; Zhao, G, 2014
)
2.57
"Dimethyl fumarate (Tecfidera®) is a novel oral therapy that has recently been approved for the treatment of relapsing forms of multiple sclerosis (MS) and relapsing-remitting MS (RRMS). "( Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis.
Burness, CB; Deeks, ED, 2014
)
3.29
"Dimethyl fumarate (DMF) is a medication approved by the US Food and Drug Administration (FDA) as an oral multiple sclerosis (MS) therapy."( Dimethyl fumarate protection against collagen II degradation.
Hu, Y; Li, Y; Tang, J, 2014
)
2.57
"Dimethyl fumarate (DMF) is a new drug used to treat multiple sclerosis (MS) patients. "( Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CD107a.
Fallang, LE; Gundersen, G; Holmøy, T; Høglund, RA; Maghazachi, AA; Sand, KL; Vego, H, 2016
)
1.88
"Dimethyl fumarate (DMF) is a fumaric acid ester that is used to treat psoriasis and multiple sclerosis. "( Dimethyl fumarate induces apoptosis of hematopoietic tumor cells via inhibition of NF-κB nuclear translocation and down-regulation of Bcl-xL and XIAP.
Fujita, A; Imano, M; Itoh, T; Nishida, S; Ogawa, N; Sakamoto, K; Satou, T; Shimaoka, H; Takeda, T; Tsubaki, M, 2014
)
3.29
"Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. "( Dimethyl fumarate suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway.
Ichikawa, M; Inaba, Y; Kim, BS; Kobayashi, K; Koh, CS; Tomiki, H, 2015
)
3.3
"Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). "( [Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate].
Matolcsi, J; Rózsa, C, 2015
)
2.09
"Dimethyl fumarate (DMF) is a chemical compound which has been added to silica gel bags used for preserving leather products during shipment. "( Quantitative determination of dimethyl fumarate in silica gel by solid-phase microextraction/gas chromatography/mass spectrometry and ultrasound-assisted extraction/gas chromatography/mass spectrometry.
Bocchini, P; Galletti, GC; Ghetti, F; Pinelli, F; Pozzi, R, 2015
)
2.15
"Dimethyl fumarate (DMF) is a newly approved drug for the treatment of relapsing forms of multiple sclerosis and relapsing-remitting multiple sclerosis. "( Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway.
Dong, DL; Gao, JL; Jin, J; Li, N; Ma, CY; Shen, X; Sun, ZJ; Wang, CG; Xie, X; Xu, XM; Zhang, YQ; Zhao, Y, 2015
)
3.3
"Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). "( The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.
Berger, J; Dukic, M; Garland, J; Khatri, BO; Kramer, J; Olapo, T; Rehn, E; Sershon, L; Sesing, J, 2015
)
2.22
"Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. "( Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.
Ambrosius, B; Gold, R; Meyer, D; Pitarokoili, K; Schrewe, L, 2015
)
3.3
"Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. "( Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells.
Altman, A; Backus, KM; Blewett, MM; Cravatt, BF; Teijaro, JR; Xie, J; Zaro, BW, 2016
)
2.18
"Dimethyl fumarate (DMF) is an approved drug for the management of relapsing multiple sclerosis. "( Enhanced Brain Delivery of Dimethyl Fumarate Employing Tocopherol-Acetate-Based Nanolipidic Carriers: Evidence from Pharmacokinetic, Biodistribution, and Cellular Uptake Studies.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
2.19
"Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis."( Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase.
Albrecht, P; Dietrich, M; Herrmann, AK; Hoffmann, C; Methner, A; Schacht, T, 2017
)
2.62
"Dimethyl Fumarate (DMF) is an FDA approved anti-oxidative and anti-inflammatory agent with a favorable safety record."( Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways.
Browning, JL; Czajka, CA; Grzegorzewska, AP; Han, R; Isenberg, JS; Makino, K; Seta, F; Stawski, L; Trojanowska, M, 2017
)
2.62
"Dimethyl fumarate is a fumaric acid ester. "( [Contact dermatitis due to dimethyl fumarate].
Giménez-Arnau, AM; Mercader, P; Silvestre, JF, 2010
)
2.1
"Dimethyl fumarate (DMFu) is a substance with remarkable hygroscopicity and fungicidal power, which has recently showed to be a strong sensitizer to humans. "( Survey of dimethyl fumarate in desiccant products during 2009 in Italy.
Dommarco, R; Girolimetti, S; Santilio, A; Stefanelli, P, 2011
)
2.21
"Dimethyl fumarate (DMF) is an effective novel treatment for multiple sclerosis in clinical trials. "( Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor κB (NF-κB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling.
Guerau-de-Arellano, M; Huss, DJ; Lovett-Racke, AE; Mehta, VB; Papenfuss, TL; Peng, H; Racke, MK; Yang, Y, 2012
)
3.26
"Dimethyl fumarate is a promising novel oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis."( Effects of dimethyl fumarate on neuroprotection and immunomodulation.
Albrecht, P; Bouchachia, I; Goebels, N; Hartung, HP; Henke, N; Hofstetter, HH; Issberner, A; Kovacs, Z; Lewerenz, J; Lisak, D; Maher, P; Mausberg, AK; Methner, A; Quasthoff, K; Zimmermann, C, 2012
)
1.49
"Dimethyl fumarate is a potent contact sensitizer and is commonly found in sachets inside furniture and footwear boxes."( Allergic contact dermatitis from dimethyl fumarate after contact with a Chinese sofa.
Doumit, J; Gavigan, G; Pratt, M,
)
1.86

Effects

Dimethyl fumarate (DMF) has been licensed for the treatment of multiple sclerosis (MS) and psoriasis; however, its role in RA is unknown. Dimethylfumarate has a long-term impact on lymphocyte biology, even after its discontinuation.

ExcerptReferenceRelevance
"Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after dimethyl fumarate."( Delayed and recurrent dimethyl fumarate induced-lymphopenia in patients with multiple sclerosis.
Borrelli, S; Goff, GL; Mathias, A; Pasquier, RD; Pot, C; Théaudin, M, 2022
)
2.48
"Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway."( Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration.
Han, H; Li, Z; Luo, D; Wang, R, 2021
)
2.79
"Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. "( Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation.
Pan, H; Wang, X; Wang, Y; Yan, C, 2021
)
3.51
"Dimethyl fumarate (DMF) has been approved for clinical treatment of multiple sclerosis based on its antioxidant and anti-inflammatory effects by activating the Nrf2 pathway. "( Dimethyl Fumarate is a Potential Therapeutic Option for Alzheimer's Disease.
Dou, Y; Sun, X; Suo, X; Xia, X; Yu, C, 2022
)
3.61
"Dimethyl fumarate (DMF) has several effects in cancer cells, including cell signaling, proliferation and cell death."( Dimethyl Fumarate Induces Apoptosis
Asano, K; Ito, S; Maeta, T; Sato, T, 2022
)
2.89
"Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after dimethyl fumarate."( Delayed and recurrent dimethyl fumarate induced-lymphopenia in patients with multiple sclerosis.
Borrelli, S; Goff, GL; Mathias, A; Pasquier, RD; Pot, C; Théaudin, M, 2022
)
2.48
"Dimethyl fumarate (DMF) has been licensed for the treatment of multiple sclerosis (MS) and psoriasis; however, its role in RA is unknown."( Dimethyl Fumarate Inhibits Fibroblast Like Synoviocytes-mediated Inflammation and Joint Destruction in Rheumatoid Arthritis.
Faramarzi, F; Rafiei, A; Rajabinejad, M; Taghadosi, M; Zafari, P, 2023
)
3.07
"Dimethyl fumarate (DMF) has antioxidant and anti-inflammatory properties and is used for multiple sclerosis treatment."( Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats.
Grembecka, B; Kurowska-Rucińska, E; Majkutewicz, I; Myślińska, D; Ruciński, J; Wrona, D, 2022
)
2.89
"Dimethyl fumarate (DMF) has shown anti-inflammatory and antioxidant activities. "( Dimethyl fumarate attenuates MSU-induced gouty arthritis by inhibiting NLRP3 inflammasome activation and oxidative stress.
Cao, Y; Hu, Y; Jin, XF; Liu, Y; Zou, JM, 2023
)
3.8
"Dimethyl fumarate (DMF) has been approved by the U.S. "( Dimethyl fumarate mitigates optic neuritis.
Berkley, C; Georgescu, C; Larabee, CM; Plafker, SM; Reyna, T; Zyla, K, 2019
)
3.4
"Dimethyl fumarate (DMF) has emerged as a first-line treatment for the relapsing-remitting multiple sclerosis (RRMS) subtype. "( A novel fumarate, isosorbide di-(methyl fumarate) (IDMF), replicates astrocyte transcriptome responses to dimethyl fumarate (DMF) but specifically down-regulates genes linked to a reactive phenotype.
Bojanowski, K; Chaudhuri, RK; Swindell, WR, 2020
)
2.21
"Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. "( Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.
Aladro, Y; Andreu-Vázquez, C; Ayuso, L; Blasco, R; Borrego, L; Casanova, I; Castro, A; Costa-Frossard, L; Díaz-Díaz, J; Galán, V; García-Domínguez, JM; García-Merino, JA; Gómez-Moreno, M; López de Silanes, C; Lozano-Ros, A; Martín, H; Meca-Lallana, V; Muñoz, C; Oreja-Guevara, C; Pilo de la Fuente, B; Rodríguez-García, E; Sabín, J; Sainz de la Maza, S; Sánchez, P; Thuissard, I, 2020
)
2.29
"Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple sclerosis treatment (Tecfidera®). "( Nanoformulations for dimethyl fumarate: Physicochemical characterization and in vitro/in vivo behavior.
Boschi, F; Calderan, L; Cortesi, R; Drechsler, M; Esposito, E; Fan, J; Fu, BM; Mannucci, S; Nastruzzi, C, 2017
)
2.22
"Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective characteristics that can be used for treatment of acute ischemic stroke."( Therapeutic effects of oral dimethyl fumarate on stroke induced by middle cerebral artery occlusion: An animal experimental study.
Borhani-Haghighi, A; Fazeli, M; Jafari, P; Namavar, MR; Safari, A; Tanideh, N, 2017
)
2.19
"Dimethyl fumarate (DMF) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases."( Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signalling by augmented antioxidation.
Fukaya, S; Itohiya, K; Kanzaki, H; Katsumata, Y; Miyamoto, Y; Nakamura, Y; Narimiya, T; Wada, S; Yamaguchi, Y, 2018
)
2.64
"Dimethyl fumarate (DMF) has been registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). "( Real-life persistence and tolerability with dimethyl fumarate.
Illes, Z; Nybo, M; Petersen, T; Sejbaek, T, 2018
)
2.18
"Dimethyl fumarate (DMF) has recently been shown to reduce the frequency of memory B cells in blood, but it is not known whether the drug influences the cellular composition in the cerebrospinal fluid (CSF)."( B-cell composition in the blood and cerebrospinal fluid of multiple sclerosis patients treated with dimethyl fumarate.
Holmøy, T; Høglund, RA; Lossius, A; Polak, J; Vartdal, F, 2018
)
1.42
"Dimethyl fumarate (DMF) has been applied for decades in the treatment of psoriasis and now also multiple sclerosis. "( Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases.
Andersen, JL; Arthur, JSC; Funder, ED; Gesser, B; Gotfred-Rasmussen, H; Gothelf, KV; Iversen, L; Nielsen, CJF; Nissen, P; Rasmussen, MK; Toth, R, 2018
)
3.37
"Dimethyl fumarate (DMF) has been recently approved for first-line monotherapy of Multiple Sclerosis (MS). "( Acute exacerbation of Hashimoto's thyroiditis in a patient treated with dimethyl fumarate for multiple sclerosis: A case report.
Bramanti, P; Ciurleo, R; D'Aleo, G; Marino, S; Rifici, C; Sessa, E, 2019
)
2.19
"Dimethyl fumarate (DMF) has been used as fungicide, but oral DMF activates anti-inflammatory and anti-oxidative pathways that are beneficial in the treatment of psoriasis. "( Dimethyl fumarate : a Janus-faced substance?
Kees, F, 2013
)
3.28
"Dimethyl fumarate has recently been approved in the USA for the treatment of relapsing-remitting MS."( Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects.
Gold, R; Linker, RA, 2013
)
2.55
"Dimethyl fumarate (DMF) has several pharmacological benefits including immunomodulation and prevention of fibrosis, which are dependent on the NF-E2-related factor 2 (Nrf2) antioxidant pathways. "( Activation of Nrf2 by dimethyl fumarate improves vascular calcification.
Bae, KH; Choi, YK; Ha, CM; Jeong, JY; Jun, do Y; Kim, JH; Lee, IK; Lee, SJ; Oh, CJ; Park, KG; Park, S, 2014
)
2.16
"Dimethyl fumarate (DMF) has been identified as being responsible for an outbreak of shoe contact dermatitis in Europe. "( Correlation between lesion site and concentration of dimethyl fumarate in different parts of shoes in patients with contact dermatitis caused by dimethyl fumarate in footwear.
Borrego, L; Cuesta, L; Pérez, M; Silvestre, JF; Toledo, F, 2011
)
2.06
"Dimethyl fumarate (DMF) has been recognized as an extremely potent irritant and sensitizer found in sachets inside furniture. "( Dimethyl fumarate contact dermatitis of the foot: an increasingly widespread disease.
Bassi, A; D'Erme, AM; Gola, M; Lotti, T, 2012
)
3.26
"Dimethyl fumarate has been successfully used in the treatment of psoriasis in the past. "( Allergic contact dermatitis from dimethyl fumarate after contact with a Chinese sofa.
Doumit, J; Gavigan, G; Pratt, M,
)
1.86

Actions

ExcerptReferenceRelevance
"Dimethyl fumarate (DMF) promotes an IL-17A"( Dimethyl fumarate-induced IL-17
Brück, J; Geisel, J; Ghoreschi, K; Glocova, I; Kellerer, C; Röcken, M, 2018
)
3.37

Treatment

Dimethyl fumarate (DMF) is a treatment for moderate-to-severe psoriasis and multiple sclerosis. It exerts pleiotropic effects on immune cells as well as CNS resident cells. Treatment reversed mechanical allodynia and hyperalgesia induced by nerve injury.

ExcerptReferenceRelevance
"Dimethyl fumarate (DMF), a treatment for multiple sclerosis, may cause leukopenia and infection. "( Interventions to Increase Leukocyte Testing during Treatment with Dimethyl Fumarate.
Burk, ML; Cunningham, FE; Gholami, P; Glassman, PA; Heidenreich, PA; Lin, S; Moore, VR; Sahay, A, 2021
)
2.3
"Dimethyl fumarate, an approved treatment for relapsing-remitting multiple sclerosis, exerts pleiotropic effects on immune cells as well as CNS resident cells. "( Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity.
Albrecht, S; Bittner, S; Derfuss, T; Diebold, M; Eveslage, M; Gross, CC; Herrmann, AM; Janoschka, C; Klotz, L; König, S; Korn, L; Kovac, S; Kuhlmann, T; Lauks, S; Liebmann, M; Luessi, F; Meuth, SG; Schmidt, S; Schneider-Hohendorf, T; Schulte-Mecklenbeck, A; Schwab, N; Wiendl, H; Wildemann, B; Zipp, F, 2021
)
3.51
"Dimethyl fumarate treatment is approved in Europe for patients with relapsing-remitting multiple sclerosis (MS) and in the US for relapsing forms of MS. "( Dimethyl fumarate treatment of primary progressive multiple sclerosis: results of an open-label extension study.
Bach Søndergaard, H; Bredahl Hansen, M; Gøbel Madsen, C; Højsgaard Chow, H; Lundell, H; Marstrand, L; Sellebjerg, F; Siebner, HR; Solberg Sørensen, P; Talbot, J, 2023
)
3.8
"Dimethyl fumarate treatment showed no effects on neither clinical nor MRI outcomes or changes in serum concentrations of NFL. "( Dimethyl fumarate treatment of primary progressive multiple sclerosis: results of an open-label extension study.
Bach Søndergaard, H; Bredahl Hansen, M; Gøbel Madsen, C; Højsgaard Chow, H; Lundell, H; Marstrand, L; Sellebjerg, F; Siebner, HR; Solberg Sørensen, P; Talbot, J, 2023
)
3.8
"Dimethyl fumarate treatment reversed mechanical allodynia (injury-vehicle, 0.45 ± 0.06 g [mean ± SD]; injury-dimethyl fumarate, 8.2 ± 0.16 g; P < 0.001) and hyperalgesia induced by nerve injury (injury-vehicle, 2 of 6 crossed noxious probes; injury-dimethyl fumarate, 6 of 6 crossed; P = 0.013). "( Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling.
Grace, PM; Kavelaars, A; Lacagnina, MJ; Li, J; Lorca, S; Ma, J; Odem, MA; Walters, ET, 2020
)
2.51
"Dimethyl fumarate (DMF) is a treatment for moderate-to-severe psoriasis and multiple sclerosis. "( Oral dimethyl fumarate induces changes within the peripheral neutrophil compartment of patients with psoriasis that are linked with skin improvement.
Gerdes, S; Morrison, PJ; Mrowietz, U; Suhrkamp, I, 2021
)
2.58
"Dimethyl fumarate treatment for 48 weeks had no effect on any of the investigated efficacy measures in patients with PPMS. "( Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis: A Randomized, Controlled Trial.
Blinkenberg, M; Buhelt, S; Gøbel Madsen, C; Holm Hansen, R; Højsgaard Chow, H; Lange, T; Lundell, H; Mahler, MR; Marstrand, L; Rode von Essen, M; Romme Christensen, J; Sellebjerg, F; Siebner, HR; Soelberg Sørensen, P; Talbot, J, 2021
)
3.51
"Dimethyl fumarate (DMF) treatment in multiple sclerosis (MS) increased the proportion of immunoregulatory CD56"( Dimethyl fumarate treatment alters NK cell function in multiple sclerosis.
Bhargava, P; Calabresi, PA; Smith, MD, 2018
)
3.37
"Dimethyl fumarate treatment was associated with a reduction in magnetic resonance imaging activity in pediatric patients; pharmacokinetic and safety profiles were consistent with those in adults. "( Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS).
Alroughani, R; Das, R; Eraly, S; Penner, N; Pultz, J; Taylor, C, 2018
)
2.19
"Treatment with dimethyl fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). "( Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia.
Becher, B; Benkert, P; Callegari, I; Claassen, M; Derfuss, T; Diebold, M; Galli, E; Ingelfinger, F; Kappos, L; Kopf, A; Kuhle, J; Núñez, NG; Sanderson, N, 2022
)
1.37

Toxicity

Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS. Infusion reactions (105 events [40·9 per 100 patient-years]) in the rituximab group were the most prevalent adverse events.

ExcerptReferenceRelevance
" Thus the toxic effects after acute GSH depletion to approximately equal to 5% of control by BSO plus dimethylfumarate (DMF) were evaluated in these same 66 cells to determine if this anti-proliferative effect could be minimized."( Toxic effects of acute glutathione depletion by buthionine sulfoximine and dimethylfumarate on murine mammary carcinoma cells.
Biaglow, JE; Dethlefsen, LA; Lehman, CM; Peck, VM, 1988
)
0.27
" Adverse events in were noted in 62% of the patients (mainly flushing and gastrointestinal complaints)."( [Efficacy and safety profile of fumaric acid esters in oral long-term therapy with severe treatment refractory psoriasis vulgaris. A study of 83 patients].
Altmeyer, P; Hartwig, R; Matthes, U, 1996
)
0.29
"It has previously been shown that rats pre-treated with butylated hydroxyanisole (BHA), a well-known inducer of the enzyme DT-diaphorase, are protected against the toxic effects of 2-methyl-1,4-naphthoquinone but are made more susceptible to the harmful action of 2-hydroxy-1,4-naphthoquinone."( Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats.
Munday, CM; Munday, R; Smith, BL, 1999
)
0.3
" It is not possible to generalize with regard to the effects of modulation of tissue levels of DT-diaphorase on naphthoquinone toxicity in vivo, since this may change not only the severity of the toxic effects, but also the target organ specificity."( Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats.
Munday, CM; Munday, R; Smith, BL, 2005
)
0.33
" Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain, flushing, and hot flush."( Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.
Dawson, KT; Eraksoy, M; Gold, R; Havrdova, E; Kappos, L; Limmroth, V; Macmanus, DG; Meluzinova, E; Miller, DH; O'Neill, GN; Polman, CH; Rektor, I; Sandrock, AW; Schmierer, K; Yang, M; Yousry, TA, 2008
)
0.35
"Fumaric acid esters (FAE) are used as an effective and safe oral treatment for plaque psoriasis in adult patients, but little is known about their efficacy and safety in children with psoriasis."( Effectiveness and safety of fumaric acid esters in children with psoriasis: a retrospective analysis of 14 patients from The Netherlands.
Arnold, WP; Balak, DM; Bousema, MT; Oostveen, AM; Seyger, MM; Thio, HB; Venema, AW, 2013
)
0.39
" No serious adverse events occurred."( Effectiveness and safety of fumaric acid esters in children with psoriasis: a retrospective analysis of 14 patients from The Netherlands.
Arnold, WP; Balak, DM; Bousema, MT; Oostveen, AM; Seyger, MM; Thio, HB; Venema, AW, 2013
)
0.39
"In this retrospective case series FAE seemed to be an effective and safe treatment for children with psoriasis."( Effectiveness and safety of fumaric acid esters in children with psoriasis: a retrospective analysis of 14 patients from The Netherlands.
Arnold, WP; Balak, DM; Bousema, MT; Oostveen, AM; Seyger, MM; Thio, HB; Venema, AW, 2013
)
0.39
" BG-12 was generally well tolerated and had an acceptable safety profile, with a similar incidence of adverse events across treatment groups."( BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety.
Cohan, SL; Dawson, KT; Fox, RJ; Henson, LJ; Kita, M; Novas, M; O'Gorman, J; Phillips, JT; Scannevin, RH; Zambrano, J, 2014
)
0.86
" Safety outcome was defined as incidences of (serious) adverse events."( Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Balak, D; Lijnen, R; Otters, E; Thio, B, 2016
)
0.43
" A total of 152 patients reported one or more adverse events, such as gastrointestinal complaints and flushing."( Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Balak, D; Lijnen, R; Otters, E; Thio, B, 2016
)
0.43
"High-dose DMF monotherapy is an effective and safe treatment option in moderate to severe psoriasis."( Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Balak, D; Lijnen, R; Otters, E; Thio, B, 2016
)
0.43
" Our study corroborates that DMF is an overall safe and effective drug that reduces relapse rate as well as disability progression in MS patients."( Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study.
Gold, R; Hartung, HP; Hoepner, R; Leussink, VI; Miclea, A, 2016
)
0.74
" Seven percent of patients experienced adverse events."( Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).
Bräu, B; Gomez, NN; Griemberg, W; Gröschel, C; Merten, K; Reich, K; Taipale, K; Weisenseel, P; Zschocke, I, 2017
)
0.46
" Adverse events associated with DMF included flushing and gastrointestinal events."( Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM.
Fernández, Ó; Fox, RJ; Giovannoni, G; Gold, R; Marantz, JL; Okwuokenye, M; Phillips, JT; Potts, J, 2017
)
0.72
"In this post hoc analysis in patients with previous IFN treatment, DMF demonstrated significant efficacy over 2 years versus placebo and an adverse event profile consistent with the overall population of DEFINE/CONFIRM."( Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM.
Fernández, Ó; Fox, RJ; Giovannoni, G; Gold, R; Marantz, JL; Okwuokenye, M; Phillips, JT; Potts, J, 2017
)
0.72
" Adverse effects of teriflunomide are well characterized and can be considered manageable."( Comparison of efficacy and safety of oral agents for the treatment of relapsing-remitting multiple sclerosis.
Bramanti, P; Guarnera, C; Mazzon, E, 2017
)
0.46
"DMF appeared generally safe and no carryover PML among investigated cases was observed."( Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events.
Bajrami, A; Calabrese, M; Castellaro, M; Farina, G; Magliozzi, R; Monaco, S; Pitteri, M, 2017
)
1.9
" Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests."( Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.
Barr, P; Elmor, R; Ernst, FR; Wong, SL, 2017
)
0.65
"One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37)."( Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.
Barr, P; Elmor, R; Ernst, FR; Wong, SL, 2017
)
0.65
" Secondary end points were pharmacokinetic parameters and adverse event incidence."( Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS).
Alroughani, R; Das, R; Eraly, S; Penner, N; Pultz, J; Taylor, C, 2018
)
0.75
" Adverse events (most commonly gastrointestinal events and flushing) and pharmacokinetic parameters were consistent with adult findings."( Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS).
Alroughani, R; Das, R; Eraly, S; Penner, N; Pultz, J; Taylor, C, 2018
)
0.75
" Most frequent adverse events (AEs) were flushing (37."( Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.
Annovazzi, P; Balgera, R; Bergamaschi, R; Bertolotto, A; Cavalla, P; Cavarretta, R; Costantini, G; D'Ambrosio, V; Ghezzi, A; La Gioia, S; Mallucci, G; Mantero, V; Matta, M; Miante, S; Montomoli, C; Perini, P; Rossi, S; Rottoli, MR; Rovaris, M; Torri-Clerici, V; Zaffaroni, M, 2018
)
0.73
"Our post-market study corroborated that DMF is a safe and effective drug."( Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.
Annovazzi, P; Balgera, R; Bergamaschi, R; Bertolotto, A; Cavalla, P; Cavarretta, R; Costantini, G; D'Ambrosio, V; Ghezzi, A; La Gioia, S; Mallucci, G; Mantero, V; Matta, M; Miante, S; Montomoli, C; Perini, P; Rossi, S; Rottoli, MR; Rovaris, M; Torri-Clerici, V; Zaffaroni, M, 2018
)
0.73
" We first evaluated DMF discontinuation rates and the incidence of adverse events and side effects."( Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study.
Boffa, L; Borriello, G; Buscarinu, MC; Centonze, D; Cortese, A; De Fino, C; De Giglio, L; Elia, G; Fantozzi, R; Ferraro, E; Francia, A; Galgani, S; Gasperini, C; Haggiag, S; Landi, D; Lucchini, M; Marfia, GA; Millefiorini, E; Mirabella, M; Monteleone, F; Nociti, V; Pozzilli, C; Prosperini, L; Salvetti, M; Sgarlata, E, 2018
)
0.79
" Adverse events (AEs) reported throughout the study period were recorded."( 72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label Extension.
Hase, M; Hiramatsu, K; Matta, A; Niino, M; Ochi, H; Onizuka, Y; Torii, S; Yun, J, 2018
)
0.76
" Adverse events (AEs) occurred in 84."( Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study.
Arnold, DL; Bidollari, I; Chen, H; Freedman, MS; Gudesblatt, M; Hanna, J; Kandinov, B; LaGanke, C; Leigh-Pemberton, R; Liu, S; Lopez-Bresnahan, M; Miller, C; Naismith, RT; Nangia, N; Obradovic, D; Rezendes, D; Wolinsky, JS; Wundes, A; Yang, L; Ziemssen, T, 2020
)
0.56
"Gastrointestinal (GI) adverse events (AEs) are commonly encountered with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing multiple sclerosis (MS)."( Nursing Management of Gastrointestinal Adverse Events Associated With Delayed-Release Dimethyl Fumarate: A Global Delphi Approach.
Campbell, TL; Edwards, M; Lefaux, BJ; Mayer, LL; Minor, C; Namey, M; Riemer, G; Robles-Sanchez, MA; White, S, 2020
)
1
" A specific database was elaborated to collect data on most frequent adverse events (AE)."( Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population.
Aladro, Y; Ayuso, L; Borrega, L; Casanova, I; Castro, A; Costa-Frossard, L; Díaz-Díaz, J; Galan, V; García-Merino, JA; Gómez-Moreno, M; López de Silanes, C; Lozano, A; Martín, H; Martínez-Ginés, ML; Meca-Lallana, V; Moreno, I; Muñoz, C; Oreja-Guevara, C; Pilo, B; Rodriguez-García, E; Sabin, J; Sainz de la Maza, S; Sanchez, P; Thuissard, I; Urtiaga, S, 2020
)
0.86
" Demographic, clinical, and imagiological characteristics were analyzed, including annualized relapse rate (ARR), Expanded Disability Status Scale, "No Evidence of Disease Activity 3," previous treatment, adverse events, treatment duration, and reason for discontinuation."( Real-Word Effectiveness and Safety of Dimethyl Fumarate in a Multiple Sclerosis Portuguese Population.
Barros, A; Brum, M; Capela, C; de Sousa, A; Parra, J; Pedrosa, R; Sequeira, J,
)
0.4
" Thirty patients (17%) discontinued treatment because of adverse drug reactions, and 21 (11."( Real-Word Effectiveness and Safety of Dimethyl Fumarate in a Multiple Sclerosis Portuguese Population.
Barros, A; Brum, M; Capela, C; de Sousa, A; Parra, J; Pedrosa, R; Sequeira, J,
)
0.4
"In this real-world audit, DMF appeared to be effective and safe for RRMS."( Real-Word Effectiveness and Safety of Dimethyl Fumarate in a Multiple Sclerosis Portuguese Population.
Barros, A; Brum, M; Capela, C; de Sousa, A; Parra, J; Pedrosa, R; Sequeira, J,
)
0.4
"To systematically review the literature for adverse events (AE) associated with DMF for MS."( Safety of dimethyl fumarate for multiple sclerosis: A systematic review and meta-analysis.
Chai, J; Liang, G; Ng, HS; Tremlett, H, 2020
)
0.96
" We examined laboratory test abnormalities and adverse health conditions in new users."( Short-term laboratory and related safety outcomes for the multiple sclerosis oral disease-modifying therapies: an observational study.
Carruthers, R; Evans, C; Kingwell, E; Marrie, RA; Tremlett, H; Walld, R; Zhang, T; Zhu, F, 2021
)
0.62
"The short-term, real-world incidences of abnormal laboratory results or adverse events were consistent with the pivotal clinical trial findings."( Short-term laboratory and related safety outcomes for the multiple sclerosis oral disease-modifying therapies: an observational study.
Carruthers, R; Evans, C; Kingwell, E; Marrie, RA; Tremlett, H; Walld, R; Zhang, T; Zhu, F, 2021
)
0.62
" The most common adverse events were lymphopenia (27),  rubefaction (16), digestive symptoms (11), fatigue (9), headache (3) and  sleep disturbances (2)."( Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis.
Boullosa-Lale, S; Crespo-Diz, C; González-Freire, L; Martínez-Martínez, L, 2020
)
0.86
"The adverse events observed in the present study are in line with those reported in previous analyses."( Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis.
Boullosa-Lale, S; Crespo-Diz, C; González-Freire, L; Martínez-Martínez, L, 2020
)
0.86
"0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs."( Comparative Efficacy and Safety of Ozanimod and Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis Using Matching-Adjusted Indirect Comparison.
Arndorfer, S; Cohan, S; Kumar, J; Tencer, T; Zhu, X; Zivkovic, M, 2021
)
0.88
"The number of psoriatic elderly patients is steadily increasing in the Western world, nevertheless they are frequently excluded from clinical trials and described as a high-risk group for adverse events."( Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study.
Bardazzi, F; Buggiani, G; Burlando, M; Campione, E; Corazza, M; Cuccia, A; Dapavo, P; Filippi, F; Parodi, A; Prignano, F; Ricceri, F; Zichichi, L, 2022
)
0.72
"Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS."( Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study.
Henderson, RD; Kiernan, MC; Mathers, S; Needham, M; Schultz, D; Vucic, S, 2021
)
2.37
" DRF has a safety/efficacy profile similar to DMF but with improved gastrointestinal (GI) tolerability and low (< 1%) treatment discontinuation due to GI adverse events (AEs)."( Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study.
Arnold, DL; Bowen, JD; Chen, H; Drulovic, J; Gudesblatt, M; Hunter, SF; Jasinska, E; Kapadia, S; Lyons, J; Mendoza, JP; Naismith, RT; Negroski, D; Shankar, SL; Singer, BA; Then Bergh, F; Wray, S; Wundes, A, 2022
)
0.72
" Infusion reactions (105 events [40·9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47·4 per 100 patient-years]) and flush (65 events [47·4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events."( Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial.
Axelsson, M; Ayad, A; Burman, J; de Flon, P; Fink, K; Frisell, T; Gilland, E; Gunnarsson, M; Hallberg, S; Hambraeus, J; Johansson, R; Lindeberg, J; Lycke, J; Mellergård, J; Nimer, FA; Piehl, F; Risedal, A; Rosenstein, I; Salzer, J; Shawket, F; Sjöblom, I; Sundström, P; Svenningsson, A, 2022
)
1.17
" However, patients taking certain oral DMTs may experience gastrointestinal (GI)-related adverse events (AEs), particularly at dose titration."( The Patient and Clinician Assessment of Gastrointestinal (GI) Related Adverse Events Associated with Oral Disease-Modifying Therapies in Multiple Sclerosis: A Qualitative Study.
Cano, S; Elliott, E; Jivraj, F; Kang, S; Kapadia, S; Reedie, S; Rock, M; Strzok, S, 2022
)
0.72
"There is a lack of safety information about the post-marketing adverse effects of several disease-modifying drugs (DMDs) used to control multiple sclerosis (MS)."( Post marketing new adverse effects of oral therapies in multiple sclerosis: A systematic review.
Ataei, S; Esfahani, ME; Jenabi, E; Sahraian, MA; Salehi, AM, 2022
)
0.72
"The oral therapies have some significant post-marketing adverse effects that have been diagnosed in numerous case reports."( Post marketing new adverse effects of oral therapies in multiple sclerosis: A systematic review.
Ataei, S; Esfahani, ME; Jenabi, E; Sahraian, MA; Salehi, AM, 2022
)
0.72
" This retrospective study aims to determine the utility of routine complete blood counts (CBC) in predicting lymphopenia, adverse effects and efficacy in a real-world clinical setting."( Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.
Baeva, ME; Camara-Lemarroy, CR; Greenfield, J; Metz, LM, 2023
)
1.12
" Higher baseline eosinophil counts predicted flushing/gastrointestinal adverse effects, and higher baseline monocyte counts were predictive of breakthrough disease activity."( Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.
Baeva, ME; Camara-Lemarroy, CR; Greenfield, J; Metz, LM, 2023
)
1.12
" Our novel findings that baseline eosinophil and monocyte counts could offer insights into usual adverse effects and efficacy, respectively, should be further investigated as a potentially new set of biomarkers."( Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.
Baeva, ME; Camara-Lemarroy, CR; Greenfield, J; Metz, LM, 2023
)
1.12
" This study aims to investigate and compare adherence, adverse event (AE) profiles, and frequencies, main reasons for treatment discontinuation under Teriflunomide (TERI), Dimethyl Fumarate (DMF), and Fingolimod (FNG) for relapsing-remitting MS (RRMS) patients."( Real-life outcomes for oral disease-modifying treatments of relapsing-remitting multiple sclerosis patients: Adherence and adverse event profiles from Marmara University.
Engin, E; Günal, D; Sünter, G; Vural, E; Yıldırım, KA, 2023
)
1.1
" The most common reasons for treatment discontinuation in order of frequency were adverse events, the progression of the disease, and the persistence of relapses."( Real-life outcomes for oral disease-modifying treatments of relapsing-remitting multiple sclerosis patients: Adherence and adverse event profiles from Marmara University.
Engin, E; Günal, D; Sünter, G; Vural, E; Yıldırım, KA, 2023
)
0.91
" Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF."( Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study.
Arnold, DL; Castro-Borrero, W; Chen, H; Drulovic, J; Freedman, MS; Gold, R; Gudesblatt, M; Hernandez Perez, MA; Jasinska, E; LaGanke, CC; Levin, S; Naismith, RT; Negroski, D; Oh, J; Scaramozza, M; Selmaj, K; Shankar, SL; Singer, BA; Then Bergh, F; Wang, T; Wray, S; Wundes, A; Ziemssen, T, 2023
)
0.91
"To compare adverse effects of immunotherapies for people with MS or clinically isolated syndrome (CIS), and to rank these treatments according to their relative risks of adverse effects through network meta-analyses (NMAs)."( Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.
Benedetti, MD; Capobussi, M; Castellini, G; Featherstone, R; Filippini, G; Frau, S; Gonzalez-Lorenzo, M; Lucenteforte, E; Perduca, V; Tramacere, I; Virgili, G, 2023
)
0.91
" Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions."( Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.
Benedetti, MD; Capobussi, M; Castellini, G; Featherstone, R; Filippini, G; Frau, S; Gonzalez-Lorenzo, M; Lucenteforte, E; Perduca, V; Tramacere, I; Virgili, G, 2023
)
0.91

Pharmacokinetics

ExcerptReferenceRelevance
" Moreover, in whole blood the half-life of DMF was dramatically reduced as compared to serum."( In vitro pharmacokinetics of anti-psoriatic fumaric acid esters.
Litjens, NH; Mattie, H; Nibbering, PH; Thio, HB; van Dissel, JT; van Gulpen, C; van Strijen, E, 2004
)
0.32
"The purpose of this study was to evaluate the tolerability and pharmacokinetic (PK) profile of DR-DMF with or without concomitant acetylsalicylic acid (aspirin), a cyclooxygenase inhibitor."( Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers.
Dawson, KT; Huang, R; Milne, GL; Nestorov, I; Novas, M; O'Gorman, J; Russell, H; Scannevin, RH; Sheikh, SI, 2013
)
0.64
" They were applied to a pharmacokinetic study in rats by a single oral dose."( Comparison of LC-UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: application to rat pharmacokinetic study.
Raja, RK; Suneetha, A, 2016
)
0.66
" Recent data suggest that a primary pharmacodynamic response to DMF treatment is activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway; however, the gene targets modulated downstream of NRF2 that contribute to DMF-dependent effects are poorly understood."( Pharmacodynamics of Dimethyl Fumarate Are Tissue Specific and Involve NRF2-Dependent and -Independent Mechanisms.
Allaire, N; Bista, P; Brennan, MS; Cullen, P; Huang, R; Lukashev, M; Patel, H; Rhodes, KJ; Ryan, S; Scannevin, RH; Thai, A, 2016
)
0.76
" Cellular uptake studies on Caco-2 and SH-SY5Y monolayers confirmed better intestinal absorption and neuronal uptake of the developed system, which was further corroborated by the pharmacokinetic and biodistribution studies."( Enhanced Brain Delivery of Dimethyl Fumarate Employing Tocopherol-Acetate-Based Nanolipidic Carriers: Evidence from Pharmacokinetic, Biodistribution, and Cellular Uptake Studies.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
0.75
"PK data showed CSF MMF concentration 11% of plasma with Tmax of plasma at 5 hr and Tmax of CSF at 7 hr."( A pharmacokinetic and biomarker study of delayed-release dimethyl fumarate in subjects with secondary progressive multiple sclerosis: evaluation of cerebrospinal fluid penetration and the effects on exploratory biomarkers.
Button, J; Edwards, KR; Kamath, A; Kamath, V; Mendoza, JP; Penner, N; Plavina, T; Woodward, C; Zhu, B, 2021
)
0.87
"PK data showed that the Tmax of CSF MMF peaked only 2 hours later than that of plasma with 11% measured in the CSF so that MMF readily crossed the blood brain barrier allowing potential direct penetration into the brain."( A pharmacokinetic and biomarker study of delayed-release dimethyl fumarate in subjects with secondary progressive multiple sclerosis: evaluation of cerebrospinal fluid penetration and the effects on exploratory biomarkers.
Button, J; Edwards, KR; Kamath, A; Kamath, V; Mendoza, JP; Penner, N; Plavina, T; Woodward, C; Zhu, B, 2021
)
0.87

Compound-Compound Interactions

ExcerptReferenceRelevance
" This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg)."( Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.
Kam, J; Leahy, M; Meka, V; Nestorov, I; Sheikh, SI; Zhao, G; Zhu, B, 2017
)
0.69

Bioavailability

ExcerptReferenceRelevance
" The developed systems not only enhanced the oral bioavailability of the drug, but also offered substantially elevated brain drug levels to that of plain drug."( Vitamin-Derived Nanolipoidal Carriers for Brain Delivery of Dimethyl Fumarate: A Novel Approach with Preclinical Evidence.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
0.7
" Our aim was to enhance the oral bioavailability and increase the brain concentrations of dimethyl fumarate."( Stearic acid based, systematically designed oral lipid nanoparticles for enhanced brain delivery of dimethyl fumarate.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
0.89

Dosage Studied

Dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans.

ExcerptRelevanceReference
"3), but the 5 mM DMF in hypoxia results in nearly a complete collapse of the hypoxic dose-response curve to the same level as seen in air with DMF."( Effect of dimethyl fumarate on the radiation sensitivity of mammalian cells in vitro.
Biaglow, JE; Clark, EP; Epp, ER; Held, KD, 1988
)
0.68
" Rats were dosed with BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), dimethyl fumarate (DMF) or disulfiram (DIS) and then challenged with a toxic dose of the naphthoquinones."( Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats.
Munday, CM; Munday, R; Smith, BL, 1999
)
0.53
" Group A received FAE tablets (Fumaderm) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle."( Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris.
Altmeyer, P; Christophers, E; Gollnick, H; Kaufmann, R; Pavel, S; Ring, J; Ziegler, J, 2002
)
0.31
" Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients."( Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters.
Altmeyer, P; Gambichler, T; Hanefeld, C; Kastner, U; Nowack, U, 2002
)
0.31
" Dosage of FAE was given according to the standard therapy regimen for psoriasis."( Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study.
Altmeyer, P; Gambichler, T; Knierim, C; Kreuter, A; Pawlak, F; Rotterdam, S; Stücker, M, 2005
)
0.33
" Additionally, acute hemodynamic and electrophysiologic effects of DMF were determined in dose-response experiments in isolated perfused rat hearts."( Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats.
Barbosa, V; Brink, M; Buser, PT; Butz, N; Fasler-Kan, E; John, D; Meili-Butz, S; Niermann, T; Zaugg, CE, 2008
)
1.79
" The median duration of FAE treatment was 10 months (range 1-80 months), and the median maintenance dosage per day was 360 mg dimethylfumarate (range 240-600 mg)."( Effectiveness and safety of fumaric acid esters in children with psoriasis: a retrospective analysis of 14 patients from The Netherlands.
Arnold, WP; Balak, DM; Bousema, MT; Oostveen, AM; Seyger, MM; Thio, HB; Venema, AW, 2013
)
0.39
" BG-12 also reduced the risk of disability progression at two years compared with placebo in most subgroups of patients treated with the BID dosing regimen and in all subgroups treated with the TID regimen."( Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study.
Arnold, DL; Bar-Or, A; Dawson, KT; Giovannoni, G; Gold, R; Kappos, L; O'Gorman, J; Selmaj, K; Stephan, M, 2013
)
0.68
" From these data, the optimal BG-12 dosage for the treatment of RRMS is 240 mg twice daily."( The fumaric acid ester BG-12: a new option in MS therapy.
Gold, R; Lee, DH; Linker, RA; Stangel, M, 2013
)
0.39
"Healthy volunteers (N = 56) were randomized to receive different dosing regimens of DR-DMF or matching placebo with or without pretreatment with 325 mg aspirin for 4 days."( Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers.
Dawson, KT; Huang, R; Milne, GL; Nestorov, I; Novas, M; O'Gorman, J; Russell, H; Scannevin, RH; Sheikh, SI, 2013
)
0.64
"This observational study recorded data on quality of life, treatment efficacy and drug dosing in patients suffering from psoriasis treated with Fumaderm under conditions of daily practice in 78 dermatological centres."( Fumaderm® in daily practice for psoriasis: dosing, efficacy and quality of life.
Adamczyk, A; Belge, K; Berner, T; Brück, J; Ghoreschi, K; Kellerer, C; Merten, K; Neureither, M; Núnez Gómez, N; Röcken, M; Walker, F, 2014
)
0.4
" At baseline and after 3, 6 and 12 months the dosing regimen under daily conditions, Dermatology Life Quality Index (DLQI) and clinical efficacy with the Psoriasis Area and Severity Index (PASI) were documented."( Fumaderm® in daily practice for psoriasis: dosing, efficacy and quality of life.
Adamczyk, A; Belge, K; Berner, T; Brück, J; Ghoreschi, K; Kellerer, C; Merten, K; Neureither, M; Núnez Gómez, N; Röcken, M; Walker, F, 2014
)
0.4
"A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010."( New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.
Aloi, JJ; English, C, 2015
)
0.42
" The DMF without ASA group (n = 43) and the DMF with ASA group (n = 43) received placebo ASA or ASA, respectively, 30 minutes before DMF (weeks 1-4), then DMF alone (weeks 5-8); in both groups, DMF was dosed at 120 mg BID (week 1) and 240 mg BID (weeks 2-8)."( Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl Fumarate.
Kurukulasuriya, NC; Li, J; O'Gorman, J; Phillips, G; Russell, HK; Viglietta, V, 2015
)
0.62
" The median daily maintenance dosage of 480 mg was reached after a median of 8 months."( Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Balak, D; Lijnen, R; Otters, E; Thio, B, 2016
)
0.43
" We compared 2 year efficacy of DMF versus fingolimod at the approved dosage using a matching-adjusted indirect approach."( Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis.
Chan, A; Edwards, MR; Fox, RJ; Levison, D; Lewin, JB; Marantz, JL; Xiao, J; Zhang, A, 2017
)
0.67
"In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period."( Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).
Bräu, B; Gomez, NN; Griemberg, W; Gröschel, C; Merten, K; Reich, K; Taipale, K; Weisenseel, P; Zschocke, I, 2017
)
0.46
" We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans."( Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans.
Brescia Morra, V; Cortopassi, G; Filla, A; Hayashi, G; Jasoliya, M; Lanzillo, R; Marsili, A; Pane, C; Puorro, G; Saccà, F; Sahdeo, S, 2017
)
2.23
" Data for DMF 240 mg BID (approved dosing regimen) are reported."( Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM.
Fernández, Ó; Fox, RJ; Giovannoni, G; Gold, R; Marantz, JL; Okwuokenye, M; Phillips, JT; Potts, J, 2017
)
0.72
" Despite immense promises, DMF is associated with various problems such as multiple dosing (2-3 oral doses daily) and lower brain permeability."( Stearic acid based, systematically designed oral lipid nanoparticles for enhanced brain delivery of dimethyl fumarate.
Katare, OP; Kumar, P; Kumar, R; Malik, R; Raza, K; Sharma, G; Singh, B, 2017
)
0.67
" Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients."( Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count.
Baharnoori, M; Chitnis, T; Chua, A; Diaz-Cruz, C; Gonzalez, CT; Healy, BC; Stankiewicz, J; Weiner, HL, 2018
)
0.7
" The studies proved the efficacy of lipid-based nanoparticles containing DMF in a once-a-day dosage regimen over that of thrice-a-day plain DMF administration on crucial parameters like motor coordination, grip strength, mortality, body weight, and locomotor activity."( Preclinical Explorative Assessment of Dimethyl Fumarate-Based Biocompatible Nanolipoidal Carriers for the Management of Multiple Sclerosis.
Gupta, V; Kaur, R; Kaushal, N; Kumar, A; Kumar, P; Malik, R; Raza, K; Sharma, G; Thakur, K, 2018
)
0.75
" While the clinical efficacy of this FAE mixture is well established, the combination of esters on which it is based, and its dosing regimen, was determined empirically."( Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data.
Amasuno, A; Asadullah, K; Landeck, L; Mrowietz, U; Pau-Charles, I, 2018
)
1.92
" Comparator DMTs were chosen to reflect different dosing regimens."( When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing-remitting multiple sclerosis.
Adlard, NE; Kroes, MA; Montgomery, SM; Noon, KM, 2018
)
0.48
" DMF was dosed twice-daily (BID) at 120 mg (week 1) and 240 mg (weeks 2-8)."( Effect of Bismuth Subsalicylate on Gastrointestinal Tolerability in Healthy Volunteers Receiving Oral Delayed-release Dimethyl Fumarate: PREVENT, a Randomized, Multicenter, Double-blind, Placebo-controlled Study.
Chalkias, S; Edwards, MR; Koulinska, I; Riester, K, 2018
)
0.69
" Lastly, DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%."( Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich's Ataxia.
Brescia Morra, V; Chedin, F; Cortopassi, G; Filla, A; Jasoliya, M; Pane, C; Pook, M; Sacca, F; Sahdeo, S, 2019
)
1.96
" Dimethyl fumarate (DMF) poses unique challenges to adherence including being the only twice-daily dosing DMT."( Assessing Barriers to Adherence with the Use of Dimethyl Fumarate in Multiple Sclerosis.
Aungst, A; Casady, L; Dixon, C; Maldonado, J; Moreo, N; Pearsall, L; Robertson, D, 2020
)
1.72
" DMF creates its own barriers to adherence with our study highlighting some, including twice-daily dosing and AEs experienced following treatment initiation."( Assessing Barriers to Adherence with the Use of Dimethyl Fumarate in Multiple Sclerosis.
Aungst, A; Casady, L; Dixon, C; Maldonado, J; Moreo, N; Pearsall, L; Robertson, D, 2020
)
0.81
" However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic."( The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.
Amor, S; Baker, D; Giovannoni, G; Kang, AS; Schmierer, K, 2020
)
0.56
" We first dosed DMF at 0-320 mg/kg in C57BL6 mice and observed significant toxicity above 160 mg/kg orally, defining the maximum tolerated dose."( Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich's ataxia model mice.
Cortopassi, G; Dedkova, EN; Hui, CK; Montgomery, C, 2021
)
2.06
" Our observation suggests prolonged and possibly irreversible lymphopenia as a possible adverse event of DMF, and it emphasizes the need for monitoring lymphocyte numbers, and to cease dosing promptly after onset of grade III lymphopenia."( Persistent severe lymphopenia 5 years after dimethyl fumarate discontinuation.
Caldito, NG; O'Leary, S; Stuve, O, 2021
)
0.88
" Blood samples were obtained prior to dosing and at prespecified time points through 24 h post-dose to determine plasma concentrations of MMF."( Pharmacokinetics and Bioavailability of Monomethyl Fumarate Following a Single Oral Dose of Bafiertam™ (Monomethyl Fumarate) or Tecfidera
Lategan, TW; Rousseau, FS; Sprague, TN; Wang, L, 2021
)
0.62
" Frequent dosing (52."( Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews.
Gudesblatt, M; Kapadia, S; Lyons, J; Roman, C; Schmidt, H; Shankar, SL; Singer, BA; Thomas, J, 2022
)
0.72
" While the oral dosing of DRF was more convenient than injectable or infusion therapy options, about half of the respondents preferred a less frequent treatment regimen than the twice daily dosing of DRF which needs to be taken with food."( Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews.
Gudesblatt, M; Kapadia, S; Lyons, J; Roman, C; Schmidt, H; Shankar, SL; Singer, BA; Thomas, J, 2022
)
0.72
" dosed drugs, including monoclonal antibodies."( Using an animal model to predict the effective human dose for oral multiple sclerosis drugs.
Benet, LZ; Liu, W; Wang, Z; Waubant, EL; Yu, Z; Zhai, S, 2023
)
0.91
" Consistent with the incubation studies, the mouse pharmacokinetic study demonstrated that alcohol decreased the maximum concentration and area-under-the-curve of MMF in the plasma and the brain after dosing with DMF."( Alcohol inhibits the metabolism of dimethyl fumarate to the active metabolite responsible for decreasing relapse frequency in the treatment of multiple sclerosis.
Laizure, SC; Meibohm, B; Parker, RB; Srivastava, A; Temrikar, ZH; Yang, B, 2022
)
1
" Oral disease-modifying therapy (DMT) offers a simple dosage form, good efficacy and safety."( Medication adherence and health outcomes in persons with multiple sclerosis treated with dimethyl fumarate.
Brecl Jakob, G; Jožef, M; Kos, M; Locatelli, I; Rot, U, 2023
)
1.13
"Eosinophilia is rare in patients with multiple sclerosis treated with DMF and usually does not require dosage adjustments."( Dimethyl fumarate induced Wells syndrome. A case report.
Aparicio-Castro, E; Candeliere-Merlicco, A; Escobar-Arias, FH; Hidalgo-Pérez, PV; Lastres-Arias, MC; Villaverde-González, R, 2023
)
2.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
immunomodulatorBiologically active substance whose activity affects or plays a role in the functioning of the immune system.
antipsoriaticA drug used to treat psoriasis.
[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
enoate esterAn alpha,beta-unsaturated carboxylic ester of general formula R(1)R(2)C=CR(3)-C(=O)OR(4) (R(4) =/= H) in which the ester C=O function is conjugated to a C=C double bond at the alpha,beta position.
methyl esterAny carboxylic ester resulting from the formal condensation of a carboxy group with methanol.
diesterA diester is a compound containing two ester groups.
[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]

Pathways (1)

PathwayProteinsCompounds
HMOX1 pathway (COVID-19 Disease Map)3630

Protein Targets (2)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Kelch-like ECH-associated protein 1Homo sapiens (human)EC50 (µMol)5.11000.87002.76005.1100AID1519148
Nuclear factor erythroid 2-related factor 2Homo sapiens (human)EC50 (µMol)5.11000.06002.61679.9000AID1519148
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (53)

Processvia Protein(s)Taxonomy
in utero embryonic developmentKelch-like ECH-associated protein 1Homo sapiens (human)
ubiquitin-dependent protein catabolic processKelch-like ECH-associated protein 1Homo sapiens (human)
regulation of autophagyKelch-like ECH-associated protein 1Homo sapiens (human)
protein ubiquitinationKelch-like ECH-associated protein 1Homo sapiens (human)
positive regulation of proteasomal ubiquitin-dependent protein catabolic processKelch-like ECH-associated protein 1Homo sapiens (human)
cellular response to oxidative stressKelch-like ECH-associated protein 1Homo sapiens (human)
negative regulation of DNA-binding transcription factor activityKelch-like ECH-associated protein 1Homo sapiens (human)
regulation of epidermal cell differentiationKelch-like ECH-associated protein 1Homo sapiens (human)
cellular response to interleukin-4Kelch-like ECH-associated protein 1Homo sapiens (human)
negative regulation of response to oxidative stressKelch-like ECH-associated protein 1Homo sapiens (human)
response to ischemiaNuclear factor erythroid 2-related factor 2Homo sapiens (human)
regulation of transcription by RNA polymerase IINuclear factor erythroid 2-related factor 2Homo sapiens (human)
inflammatory responseNuclear factor erythroid 2-related factor 2Homo sapiens (human)
response to oxidative stressNuclear factor erythroid 2-related factor 2Homo sapiens (human)
proteasomal ubiquitin-independent protein catabolic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of gene expressionNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of cardiac muscle cell apoptotic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of neuron projection developmentNuclear factor erythroid 2-related factor 2Homo sapiens (human)
protein ubiquitinationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of blood coagulationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
endoplasmic reticulum unfolded protein responseNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to oxidative stressNuclear factor erythroid 2-related factor 2Homo sapiens (human)
PERK-mediated unfolded protein responseNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to glucose starvationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of blood vessel endothelial cell migrationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
regulation of innate immune responseNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cell redox homeostasisNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of angiogenesisNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of transcription by RNA polymerase IINuclear factor erythroid 2-related factor 2Homo sapiens (human)
regulation of embryonic developmentNuclear factor erythroid 2-related factor 2Homo sapiens (human)
aflatoxin catabolic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of glucose importNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to hydrogen peroxideNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to copper ionNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to tumor necrosis factorNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to hypoxiaNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to xenobiotic stimulusNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to fluid shear stressNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to laminar fluid shear stressNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of ferroptosisNuclear factor erythroid 2-related factor 2Homo sapiens (human)
integrated stress response signalingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of cellular response to hypoxiaNuclear factor erythroid 2-related factor 2Homo sapiens (human)
regulation of cellular response to oxidative stressNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of hematopoietic stem cell differentiationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathwayNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of glutathione biosynthetic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of ERAD pathwayNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cellular response to angiotensinNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of vascular associated smooth muscle cell migrationNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of ubiquitin-dependent protein catabolic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
regulation of removal of superoxide radicalsNuclear factor erythroid 2-related factor 2Homo sapiens (human)
negative regulation of endothelial cell apoptotic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
positive regulation of reactive oxygen species metabolic processNuclear factor erythroid 2-related factor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (17)

Processvia Protein(s)Taxonomy
protein bindingKelch-like ECH-associated protein 1Homo sapiens (human)
identical protein bindingKelch-like ECH-associated protein 1Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingKelch-like ECH-associated protein 1Homo sapiens (human)
disordered domain specific bindingKelch-like ECH-associated protein 1Homo sapiens (human)
ubiquitin-like ligase-substrate adaptor activityKelch-like ECH-associated protein 1Homo sapiens (human)
transcription factor bindingKelch-like ECH-associated protein 1Homo sapiens (human)
transcription cis-regulatory region bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificNuclear factor erythroid 2-related factor 2Homo sapiens (human)
transcription coregulator bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificNuclear factor erythroid 2-related factor 2Homo sapiens (human)
DNA bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
DNA-binding transcription factor activityNuclear factor erythroid 2-related factor 2Homo sapiens (human)
protein bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
protein domain specific bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
ubiquitin protein ligase bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
sequence-specific DNA bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
molecular condensate scaffold activityNuclear factor erythroid 2-related factor 2Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingNuclear factor erythroid 2-related factor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (18)

Processvia Protein(s)Taxonomy
nucleoplasmKelch-like ECH-associated protein 1Homo sapiens (human)
cytoplasmKelch-like ECH-associated protein 1Homo sapiens (human)
endoplasmic reticulumKelch-like ECH-associated protein 1Homo sapiens (human)
cytosolKelch-like ECH-associated protein 1Homo sapiens (human)
actin filamentKelch-like ECH-associated protein 1Homo sapiens (human)
inclusion bodyKelch-like ECH-associated protein 1Homo sapiens (human)
midbodyKelch-like ECH-associated protein 1Homo sapiens (human)
centriolar satelliteKelch-like ECH-associated protein 1Homo sapiens (human)
Cul3-RING ubiquitin ligase complexKelch-like ECH-associated protein 1Homo sapiens (human)
mediator complexNuclear factor erythroid 2-related factor 2Homo sapiens (human)
non-membrane-bounded organelleNuclear factor erythroid 2-related factor 2Homo sapiens (human)
nucleusNuclear factor erythroid 2-related factor 2Homo sapiens (human)
nucleoplasmNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cytoplasmNuclear factor erythroid 2-related factor 2Homo sapiens (human)
Golgi apparatusNuclear factor erythroid 2-related factor 2Homo sapiens (human)
centrosomeNuclear factor erythroid 2-related factor 2Homo sapiens (human)
cytosolNuclear factor erythroid 2-related factor 2Homo sapiens (human)
plasma membraneNuclear factor erythroid 2-related factor 2Homo sapiens (human)
RNA polymerase II transcription regulator complexNuclear factor erythroid 2-related factor 2Homo sapiens (human)
chromatinNuclear factor erythroid 2-related factor 2Homo sapiens (human)
protein-DNA complexNuclear factor erythroid 2-related factor 2Homo sapiens (human)
nucleusNuclear factor erythroid 2-related factor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (68)

Assay IDTitleYearJournalArticle
AID1822759Inhibition of wild type Candida albicans Fructose-1,6-Bisphosphate Aldolase transfected in Escherichia coli BL21 (DE3) at 50 uM incubated for 3 mins in presence of NADH by spectrophotometric analysis relative to control2022Journal of medicinal chemistry, 02-10, Volume: 65, Issue:3
Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of
AID1728770Anti-necroptotic activity in human HT-29 cells assessed as inhibition of TNFalpha/SM-164/Z-VAD-fmk (TSZ)-induced necroptosis by measuring increase in cell viability at 10 uM measured after 12 hrs by celltiter-glo luminescent cell viability assay2021European journal of medicinal chemistry, Feb-15, Volume: 212Discovery of bardoxolone derivatives as novel orally active necroptosis inhibitors.
AID1432752Cytotoxicity against mouse BALB/3T3 cells assessed as reduction in cell proliferation after 72 hrs by SRB assay2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1687067Inhibition of recombinant cathepsin B (unknown origin) endopeptidase activity expressed in Escherichia coli assessed as residual activity at 100 uM using Z-RR-AMC as substrate preincubated for 30 mins under shaking in presence of 5 mM cysteine followed by2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1687062Inhibition of Escherichia coli MurA using UNAG and PEP as substrate preincubated for 30 mins in presence of UNAG followed by PEP addition and measured after 15 mins by malachite green colorimetric assay2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1687065Inhibition of Escherichia coli MurA assessed as residual activity at 100 uM using UNAG and PEP as substrate preincubated for 30 mins in presence of UNAG followed by PEP addition and measured after 15 mins by malachite green colorimetric assay relative to 2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1063372Inhibition of human HPGD in human ME180 cells assessed as downregulation of TNFalpha-induced NF-kappaB expression at 647 pM to 38.2 uM incubated for 15 mins prior to TNFalpha addition measured after 4 to 24 hrs by beta-lactamase reporter gene assay2014Bioorganic & medicinal chemistry letters, Jan-15, Volume: 24, Issue:2
Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors.
AID1230966Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 160 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID1136542Antifungal activity against Aspergillus niger ATCC 1004 at <100 ug/ml at pH 5.6 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1763200Inhibition of TET in human THP-1 cells assessed as reduction in 5hmc/5mc level at 50 uM incubated for 12 hrs by dot blot analysis relative to control2021Bioorganic & medicinal chemistry, 06-01, Volume: 39SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates.
AID1726792GSH reactivity assessed as pseudo first order rate constant at 1 mM in presence of glutathione2021RSC medicinal chemistry, Jun-23, Volume: 12, Issue:6
Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach.
AID1726793GSH reactivity assessed as half life at 1 mM in presence of glutathione2021RSC medicinal chemistry, Jun-23, Volume: 12, Issue:6
Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach.
AID1136549Antifungal activity against Mucor mucedo ATCC 7941 at pH 5.6 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1517970Inhibition of human FBPase expressed in Escherichia coli BL21 (DE3) at 500 uM using FBP as substrate incubated for 5 mins by malachite green dye based spectrophotometry relative to control2019European journal of medicinal chemistry, Dec-15, Volume: 184Discovery of novel allosteric site and covalent inhibitors of FBPase with potent hypoglycemic effects.
AID1447613Inhibition of recombinant human NLRP3 ATPase assessed as hydrolysis of ATP at 100 uM preincubated for 15 mins followed by addition of ATP measured after 40 mins by ADP-Glo assay2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1687068Inhibition of recombinant cathepsin B (unknown origin) exopeptidase activity expressed in Escherichia coli assessed as residual activity at 100 uM using Abz-GIVRAK(Dnp)-OH as substrate preincubated for 30 mins under shaking in presence of 5 mM cysteine fo2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1230961Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 0.2 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID1136567Antifungal activity against Candida albicans ATCC 10231 at pH 7 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1519148Activation of NRF2 in human U2OS cells co-expressing Keap1 (unknown origin) assessed as induction of NRF2 translocation to nucleus incubated for 6 hrs by beta-galactosidase based chemiluminescent assay2020European journal of medicinal chemistry, Jan-01, Volume: 185A novel chalcone derivative as Nrf2 activator attenuates learning and memory impairment in a scopolamine-induced mouse model.
AID757415Activation of Nrf2 in human DLD1 cells after 24 to 48 hrs by luciferase reporter gene assay2013Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
AID1136565Antifungal activity against Candida albicans ATCC 10231 at pH 5.6 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136546Antifungal activity against Aspergillus niger ATCC 1004 at <100 ug/ml at pH 7 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1432760Inhibition of Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production by measuring steady state enzyme-inhibitor complex using urea as substrate measured for 120 mins by phenol-hypochlorite method2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1348750Cytotoxicity against human MCF7 cells assessed as decrease in cell viability at 15 uM by MTT assay2018Journal of natural products, 03-23, Volume: 81, Issue:3
Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.
AID1432755Competitive inhibition of Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production preincubated with enzyme followed by addition of varying levels of urea as substrate measured for 120 mins by Lineweaver-Burk plot analysis2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1687064Inhibition of Staphylococcus aureus MurA expressed in Escherichia coli assessed as residual activity at 100 uM using UNAG and PEP as substrate preincubated for 30 mins in presence of UNAG followed by PEP addition and measured after 15 mins by malachite gr2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1432763Glutathione reactivity in pH 7.4 PBS measured after 6 to 36 hrs in presence of 1.375 mmol GSH by DTNB reagent based spectrophotometric method2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1230964Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 40 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID757417Binding affinity to human recombinant Kelch-DC domain of Keap1 (321 to 609) expressed in HEK293T cells assessed as covalent adduct formation with cysteines at 1 mM after 15 hrs by 2D-FIDA assay2013Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
AID1687071Inhibition of Escherichia coli MurA assessed as residual activity at 1 mM using UNAG and PEP as substrate preincubated for 30 mins in presence of UNAG followed by PEP addition and measured after 15 mins by malachite green colorimetric assay relative to co2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1432756Reversible inhibition of Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production by measuring recovery of enzyme activity at 10 times IC50 preincubated for 60 mins followed by 100-fold dilution in to PBS containing urea as subst2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1230963Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 2 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID757416Activation of Nrf2 in human DLD1 cells assessed as stabilization of Nrf2 protein at 20 uM after 48 hrs by Western blot analysis2013Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
AID1136544Antifungal activity against Aspergillus niger ATCC 1004 at <100 ug/ml at pH 7 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136561Antifungal activity against Trichophyton mentagrophytes ATCC 9129 at pH 7 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1447676Inhibition of NLRP3 inflammasome in LPS-primed C57BL/6 mouse bone marrow derived macrophages assessed as reduction in ATP-induced pyroptosis at 1 to 100 uM preincubated for 1 hr followed by stimulation with ATP measured after 30 mins by LDH release assay2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1136557Antifungal activity against Trichophyton mentagrophytes ATCC 9129 at pH 5.6 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1348749Activation of Keap1/Nrf2 in human MCF7 cells assessed as Nrf2 stabilization at 15 uM incubated overnight by luciferase reporter gene based luminescence assay2018Journal of natural products, 03-23, Volume: 81, Issue:3
Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.
AID1432761Glutathione reactivity up to 15 mins in presence of 10 mM GSH by 1H NMR analysis2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1763199Inhibition of TET in human THP-1 cells assessed as reduction in 5hmc/5mc level at 25 uM incubated for 12 hrs by dot blot analysis relative to control2021Bioorganic & medicinal chemistry, 06-01, Volume: 39SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates.
AID1230965Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 80 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID1136553Antifungal activity against Mucor mucedo ATCC 7941 at pH 7 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136551Antifungal activity against Mucor mucedo ATCC 7941 at pH 7 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1447677Inhibition of NLRP3 inflammasome in LPS-primed C57BL/6 mouse bone marrow derived macrophages assessed as reduction in nigericin-induced pyroptosis at 1 to 100 uM preincubated for 1 hr followed by stimulation with ATP measured after 30 mins by LDH release 2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1447621Inhibition of NLRP3 inflammasome in LPS-primed C57BL/6 mouse bone marrow derived macrophages assessed as reduction in nigericin-induced IL-1beta production at 1 to 100 uM preincubated for 1 hr followed by stimulation with nigericin measured after 30 mins 2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1900358Cytotoxicity against HEK293T cells assessed as reduction in cell viability at 20 uM measured after 16 hrs by MTT assay2022Journal of medicinal chemistry, 02-10, Volume: 65, Issue:3
Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis.
AID1136569Antifungal activity against Candida albicans ATCC 10231 at pH 7 after 5 days in presence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136555Antifungal activity against Trichophyton mentagrophytes ATCC 9129 at pH 5.6 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136559Antifungal activity against Trichophyton mentagrophytes ATCC 9129 at pH 7 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1447611Cytotoxicity against human THP1 cells assessed as reduction in cell viability after 72 hrs by MTT assay2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1432759Inhibition of Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production by measuring initial state enzyme-inhibitor complex using urea as substrate measured for 120 mins by phenol-hypochlorite method2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1230962Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 0.02 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID1763201Inhibition of TET in human THP-1 cells assessed as reduction in 5hmc/5mc level at 100 uM incubated for 12 hrs by dot blot analysis relative to control2021Bioorganic & medicinal chemistry, 06-01, Volume: 39SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates.
AID1136547Antifungal activity against Mucor mucedo ATCC 7941 at pH 5.6 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1136572Antifungal activity against Aspergillus niger ATCC 1004 at <100 ug/ml at pH 5.6 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1230959Activation of Nrf2 in human HepG2-ARE-C8 cells assessed as upregulation of ARE level at 20 uM after 12 hrs by luciferase reporter gene assay relative to control2015Journal of medicinal chemistry, Jul-23, Volume: 58, Issue:14
Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure-Activity Relationship Study.
AID1432754Time-dependent Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production using urea as substrate by phenol-hypochlorite method2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1687066Inhibition of Escherichia coli MurA assessed as residual activity at 100 uM using UNAG and PEP as substrate preincubated for 30 mins in presence of UNAG followed by PEP addition and measured after 15 mins in presence of 5 mM cysteine by malachite green co2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID757414Activation of Nrf2 in human DLD1 cells assessed as increase of NQO1 protein level at 20 uM after 48 hrs by Western blot analysis2013Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14
Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
AID1900359Cytotoxicity against HEK293T cells assessed as reduction in cell viability at 60 uM measured after 16 hrs by MTT assay2022Journal of medicinal chemistry, 02-10, Volume: 65, Issue:3
Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis.
AID1447605Cysteamine reactivity of the compound in PBS assessed as second order rate constant for free cysteamine release at 250 uM and pH 7.4 after 90 mins by DTNB reagent based RP-UHPLC analysis2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1136563Antifungal activity against Candida albicans ATCC 10231 at pH 5.6 after 5 days in absence of 10% beef serum1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
AID1447620Inhibition of NLRP3 inflammasome in LPS-primed C57BL/6 mouse bone marrow derived macrophages assessed as reduction in ATP-induced IL-1beta production at 1 to 100 uM preincubated for 1 hr followed by stimulation with ATP measured after 30 mins by ELISA2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1432751Inhibition of Sporosarcina pasteurii CCM 2056 urease assessed as reduction in ammonia production using urea as substrate measured for 120 mins by phenol-hypochlorite method2017Bioorganic & medicinal chemistry letters, 03-15, Volume: 27, Issue:6
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling.
AID1447615Inhibition of NLRP3 in PMA-differentiated and LPS-primed human THP1 cells assessed as decrease in ATP-induced pyroptosis measured as LDH activity at 10 uM preincubated for 1 hr followed by ATP addition measured after 1 hr by colorimetric assay relative to2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
AID1687069Inhibition of recombinant cathepsin X (unknown origin) expressed in Pichia pastoris assessed as residual activity at 100 uM using Abz-Fek(Dnp)-OH as substrate preincubated for 30 mins under shaking in presence of 5 mM cysteine followed by substrate additi2018European journal of medicinal chemistry, Dec-05, Volume: 160A road map for prioritizing warheads for cysteine targeting covalent inhibitors.
AID1447614Inhibition of recombinant human NLRP3 ATPase assessed as hydrolysis of ATP at 50 uM preincubated for 15 mins followed by addition of ATP measured after 40 mins by ADP-Glo assay2017Journal of medicinal chemistry, 05-11, Volume: 60, Issue:9
Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,020)

TimeframeStudies, This Drug (%)All Drugs %
pre-19904 (0.39)18.7374
1990's27 (2.65)18.2507
2000's81 (7.94)29.6817
2010's550 (53.92)24.3611
2020's358 (35.10)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 70.95

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 Index70.95 (24.57)
Research Supply Index7.02 (2.92)
Research Growth Index5.86 (4.65)
Search Engine Demand Index123.09 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (70.95)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials71 (6.78%)5.53%
Reviews144 (13.75%)6.00%
Case Studies98 (9.36%)4.05%
Observational45 (4.30%)0.25%
Other689 (65.81%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (97)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized, Controlled, Multicenter, Open Label Study With Blinded Assessment of the Efficacy of the Humanized Anti-IL-23p19 Risankizumab Compared to FUMADERM® in Subjects With Moderate to Severe Plaque Psoriasis Who Are Naïve to and Candidates for Syst [NCT03255382]Phase 3120 participants (Actual)Interventional2017-08-22Completed
A Pharmacokinetics Profile Determination of BG00012 Standard Formulation and the BG00012 Active Pharmaceutical Ingredient (API) After a Single Oral Dose Administered to Healthy Male Volunteers [NCT01069913]Phase 114 participants (Actual)Interventional2009-10-31Completed
Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry [NCT05658497]908 participants (Anticipated)Observational [Patient Registry]2023-10-27Recruiting
A Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Pharmacokinetics of BG00012 Administered With and Without 325 mg Aspirin in Healthy Adult Volunteers [NCT01281111]Phase 156 participants (Actual)Interventional2011-02-01Completed
Open-Label Rater-Blind Randomized Multi-Center Parallel-Arm Active- Comparator Study to Assess the Efficacy and Tolerability of Ofatumumab 20mg SC Monthly vs. First Line DMT - Physician's Choice in the Treatment of Newly Diagnosed RMS [NCT04788615]Phase 3186 participants (Anticipated)Interventional2021-07-23Recruiting
A Phase 3 Study in Subjects With Relapsing Remitting Multiple Sclerosis to Evaluate the Tolerability of ALKS 8700 and Dimethyl Fumarate [NCT03093324]Phase 3506 participants (Actual)Interventional2017-03-15Completed
Randomised Evaluation of COVID-19 Therapy [NCT04381936]Phase 2/Phase 350,000 participants (Anticipated)Interventional2020-03-19Recruiting
A Double-blinded, Placebo-controlled Pilot Study of Dimethyl Fumarate (DMF) in Pulmonary Arterial Hypertension (PAH) Associated With Systemic Sclerosis (SSc-PAH): The Effect of DMF on Clinical Disease and Biomarkers of Oxidative Stress. [NCT02981082]Phase 16 participants (Actual)Interventional2016-12-31Terminated(stopped due to Low recruitment)
A Single-Dose, Randomized, Open-Label, 2-Way Crossover, Comparative Bioavailability Study of BLS-11 (Monomethyl Fumarate) 190 mg and Tecfidera (Dimethyl Fumarate) 240 mg in Healthy Male and Female Subjects Under Fasting Conditions [NCT04570670]Phase 150 participants (Actual)Interventional2017-01-06Completed
A Multicenter, Open-Label Study to Evaluate Fatigue in Subjects With Relapsing-Remitting Multiple Sclerosis During Treatment With Tecfidera® (Dimethyl Fumarate) Gastro-Resistant Hard Capsules (TECNERGY) [NCT02090348]Phase 40 participants (Actual)Interventional2015-06-30Withdrawn(stopped due to The study was withdrawn for business reasons. The decision to stop the TECNERGY study was not a result of any safety or efficacy concerns.)
Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms: a Double Blind Randomized Controlled Trail [NCT05959759]Phase 460 participants (Anticipated)Interventional2023-07-31Not yet recruiting
Long-Term Analysis of DImethyl Fumarate, to Slow the Growth of Areas of Geographic Atrophy [NCT04292080]Phase 260 participants (Anticipated)Interventional2022-02-07Recruiting
Phase IV, Interventional, multicenteR, Double-blind, Randomized, Placebo-controlled Study tO Explore the Onset of Efficacy on Magnetic Resonance Disease Activity of BG00012 (Dimethyl Fumarate) in Patients With relapsingremitTing Multiple Sclerosis [NCT02472938]Phase 40 participants (Actual)Interventional2015-07-31Withdrawn(stopped due to Sponsor Decision)
A Multicenter, Open-Label, 12-Month Observational Study Evaluating the Clinical Effectiveness and Impact on Patient-Reported Outcomes of Oral Tecfidera™ (Dimethyl Fumarate) Delayed-Release Capsules in Patients With Relapsing-Remitting Multiple Sclerosis, [NCT02323269]24 participants (Actual)Observational2015-05-31Terminated(stopped due to 109MS415 ImPROve study was terminated due to patient enrollment challenges and feasibility . The decision was not a result of safety concerns.)
Czech Pharmaco-epidemiological Real World Data Study Focused on Effectiveness of Different Disease Modifying Drugs [NCT05762003]17,478 participants (Actual)Observational2019-01-01Completed
Phase I Clinical Trial to Evaluate Dimethylfumarate (DMF) in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. [NCT02784834]Phase 12 participants (Actual)Interventional2016-06-30Terminated(stopped due to lack of funding)
A Randomized, Double-Blind, Crossover Study in Healthy Volunteers to Establish the Bioequivalence of BG00012 Supplied by 2 Different Commercial Manufacturers (Vifor SA and Biogen Idec OSD) [NCT02171208]Phase 180 participants (Actual)Interventional2014-06-30Completed
Effect of Teriflunomide on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective Observational Case-control Pilot Study [NCT03526224]120 participants (Actual)Observational2018-06-14Completed
A Multicentric Randomized PRAGmatic Trial to Compare the Effectiveness of Fingolimod Versus Dimethyl-Fumarate on Patient Overall Disease Experience in Relapsing Remitting Multiple Sclerosis: Novel Data to Inform Decision-makers [NCT03345940]Phase 455 participants (Actual)Interventional2017-04-30Terminated(stopped due to termination of the study due to the slowness of the recruitment activity, according to the contract signed with the Sponsor)
A Randomized, Double Blind, Placebo-controlled Proof-of-concept Study of FP187 in Patients With Mild to Moderate Psoriatic Arthritis [NCT02475304]Phase 20 participants (Actual)Interventional2015-05-31Withdrawn(stopped due to Difficulties to enrol patients)
The Effect of Tecfidera® (Dimethyl Fumarate, BG00012) on the Gut Microbiota as a Causal Factor for Gastro Intestinal Associated Adverse Events. [NCT02471560]Phase 436 participants (Actual)Interventional2015-11-06Completed
Efficacy and Safety of Fumaric Acid Esters (Fumaderm®) in the Treatment of Patients With Cutaneous Lupus Erythematosus: A Mono-Centre, Open-Label, Prospective Pilot Study [NCT01352988]Phase 211 participants (Actual)Interventional2011-07-31Completed
An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis [NCT02683863]Phase 420 participants (Anticipated)Interventional2015-08-31Completed
A Phase I/II Dose Escalation/Adaptive Design Study to Evaluate the Safety and Efficacy of IMCY-0141 in Patients With Relapsing Remitting-Multiple Sclerosis (RR-MS) [NCT05417269]Phase 1/Phase 2150 participants (Anticipated)Interventional2022-04-12Recruiting
Chi3L1: A Marker of Efficacy of Platform Treatments in Relapsing-onset Multiple Sclerosis: A Prognostic Study on Existing Clinical Data and Biological Samples [NCT04289675]63 participants (Actual)Observational [Patient Registry]2012-01-01Completed
A Multicenter, Retrospective, Observational Study Evaluating Real-world Clinical Outcomes in Relapsing-remitting Multiple Sclerosis Patients Who Transition From Tysabri® (Natalizumab) to Tecfidera® (Dimethyl Fumarate) [NCT02159573]530 participants (Actual)Observational2014-07-31Completed
Multi-center, Randomized, Double-blinded Assessment of Tecfidera® in Extending the Time to a First Attack in Radiologically Isolated Syndrome (RIS) (ARISE) [NCT02739542]Phase 487 participants (Actual)Interventional2016-03-19Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of BG00012 in Delaying Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis [NCT02430532]Phase 358 participants (Actual)Interventional2015-05-31Terminated(stopped due to Sponsor Decision)
Combination of the Immune Modulator Dimethyl Fumarate With Intraarterial Treatment in Acute Ischemic Stroke [NCT04891497]Phase 20 participants (Actual)Interventional2021-06-01Withdrawn(stopped due to There are no suitable patients)
Dimethyl Fumarate for the Treatment of Intracerebral Hemorrhage [NCT04890379]Phase 20 participants (Actual)Interventional2021-06-01Withdrawn(stopped due to There are no sufficient patients in the hospital.)
Impact of an Immune Modulator Dimethyl Fumarate on Acute Ischemic Stroke [NCT04890353]Phase 1/Phase 22 participants (Actual)Interventional2021-12-01Terminated(stopped due to The interim analysis of another associated study is not very effective)
Single Country Study Assessing Cognition in Relapsing Remitting Multiple Sclerosis Patients Treated With BG00012 [NCT02579681]Phase 3221 participants (Actual)Interventional2014-04-30Completed
A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 3-Arm, Parallel Group Study in Pediatric Subjects Aged 10 Through 17 Years to Evaluate the Efficacy and Safety of BG00012 and BIIB017 for the Treatment of Relapsing-Remitting Multiple Sclerosis [NCT03870763]Phase 311 participants (Actual)Interventional2019-03-19Terminated(stopped due to Decision to stop the trial was based on long-term difficulties in fulfilling our enrolment commitments and changes in paediatric MS landscape which no longer support placebo-controlled trials.Decision to stop study was not based on safety concerns.)
A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biologica [NCT02975349]Phase 2267 participants (Actual)Interventional2017-03-07Active, not recruiting
Modulation of Cerebral Grey Matter High Energy Phosphate Metabolites in Multiple Sclerosis by Dimethyl Fumarate [NCT02644083]4 participants (Actual)Observational2016-02-29Terminated
A Retrospective Analysis in Real World on Lymphocyte Reconstitution After Lymphopenia in Patients Treated by Tecfidera and Description of Management Strategies in France [NCT04756687]1,507 participants (Actual)Observational2021-03-10Completed
Monitoring of Patients Followed for a Multiple Sclerosis and Treated by Dimethyl-fumarate SURV-SEP [NCT02901106]Phase 411 participants (Actual)Interventional2017-05-23Terminated(stopped due to Another surveillance protocol was initiated by the OFSEP (OFSEP cohort) which allows to follow all the patients, whatever their treatment.)
A 24-Hour Pharmacokinetic Determination of BG00012 After Single-Day Oral Administration in Subjects With Multiple Sclerosis [NCT00837785]Phase 148 participants (Actual)Interventional2009-02-28Completed
Double-Blind, Placebo-Controlled, Dose-Ranging Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis [NCT00168701]Phase 2260 participants (Actual)Interventional2004-10-01Completed
Effectiveness and Safety of Generic Delayed-Release Dimethyl Fumarate (Sclera® or Marovarex ®, Hikma) in Routine Medical Practice in the Treatment of Relapsing-Remitting Multiple Sclerosis in MENA Region [NCT04468165]160 participants (Actual)Observational2021-02-23Completed
A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis [NCT00835770]Phase 31,736 participants (Actual)Interventional2009-02-03Completed
Mechanisms of Action of Dimethyl Fumarate in Relapsing MS [NCT02675413]Phase 40 participants (Actual)Interventional2016-04-30Withdrawn(stopped due to Principal Investigator decided to withdraw.)
RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis. A Randomized Phase 3 Study Comparing Rituximab With Dimethyl Fumarate in Early Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome. [NCT02746744]Phase 3200 participants (Actual)Interventional2016-05-31Completed
Biogen Idec Multiple Sclerosis Pregnancy Exposure Registry [NCT01911767]408 participants (Actual)Observational [Patient Registry]2013-10-30Completed
Patient Real-world Clinical, Neurological, Tolerability, and Safety Outcomes for Tecfidera® and Rebif®: A Retrospective Study (PROTRACT) [NCT02823951]479 participants (Actual)Observational2016-02-29Completed
Measuring the Impact of Tecfidera on the Gut Microbiota: Does a Change in the Gut Flora Correlate With Gastrointestinal Disturbances Following Therapy Initiation? [NCT02736279]25 participants (Anticipated)Observational2015-05-31Recruiting
A Multicenter, Open-Label Study Evaluating the Effectiveness of Oral Tecfidera™ (Dimethyl Fumarate) on MS Disease Activity and Patient-Reported Outcomes in Subjects With Relapsing-Remitting Multiple Sclerosis in the Real-World Setting [NCT01930708]Phase 41,114 participants (Actual)Interventional2013-10-31Completed
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study to Evaluate the Efficacy, Safety and Tolerability of BG00012 When Given With Methotrexate to Subjects With Active RA Who Have Had an Inadequate Response to Conventional Disease-Mo [NCT00810836]Phase 2153 participants (Actual)Interventional2008-12-31Completed
Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients [NCT03092544]Phase 457 participants (Actual)Interventional2015-02-28Active, not recruiting
A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis [NCT00420212]Phase 31,234 participants (Actual)Interventional2007-01-31Completed
A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis [NCT00451451]Phase 31,417 participants (Actual)Interventional2007-06-30Completed
A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral ALKS 8700 in Healthy Adults [NCT02201849]Phase 1104 participants (Actual)Interventional2014-07-31Completed
A Multicenter, Open-Label, 12-Month Observational Study Evaluating the Clinical Effectiveness and Impact on Patient-Reported Outcomes of Oral Tecfidera™ (Dimethyl Fumarate) Delayed-Release Capsules in Patients With Relapsing Forms of Multiple Sclerosis Af [NCT01903291]333 participants (Actual)Observational2013-08-31Completed
A Multicenter, Double Blind, Placebo-Controlled Study of Pepto-Bismol® (Bismuth Subsalicylate) on Gastrointestinal Tolerability in Healthy Volunteers Receiving Oral TECFIDERA™ (Dimethyl Fumarate) Delayed-Release Capsules Twice Daily [NCT01915901]Phase 1175 participants (Actual)Interventional2013-08-31Completed
Study on the Dimethyl Fumarate (DMF, Tecfidera®) Persistence of Remitting-relapsing Multiple Sclerosis (RR-MS) Patients Included in the French Patient Support Program (PSP) OroSEP [NCT04221191]353 participants (Actual)Observational2019-08-19Completed
The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial. [NCT04260711]130 participants (Anticipated)Interventional2020-07-01Recruiting
An Open-label, Observational, Single-blinded, Longitudinal Study to Evaluate the Effect of Dimethyl Fumarate on Gray and White Matter Pathology in Subjects With Relapsing Multiple Sclerosis [NCT02686684]115 participants (Actual)Observational2015-11-30Completed
Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis [NCT03535298]Phase 4800 participants (Anticipated)Interventional2019-01-03Recruiting
Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis [NCT02959658]Phase 254 participants (Actual)Interventional2016-12-31Completed
Combination of the Immune Modulator Dimethyl Fumarate With Alteplase in Acute Ischemic Stroke [NCT04890366]Phase 1/Phase 250 participants (Anticipated)Interventional2021-12-01Recruiting
Study to Investigate the Pharmacokinetics, Safety, and Tolerability of BG00012 (Dimethyl Fumarate) When Delivered to Different Regions of the Gastrointestinal Tract in Healthy Subjects [NCT01924832]Phase 132 participants (Actual)Interventional2013-08-31Completed
An Open-Label, Multicenter Study in Subjects With Relapsing-Remitting Multiple Sclerosis to Evaluate the Safety of 240 mg BG00012 TID Administered as Add-On Therapy to Beta Interferons (IFNβ) or Glatiramer Acetate (GA) [NCT01156311]Phase 2108 participants (Actual)Interventional2010-06-30Completed
Randomized, Open-label, Single-center, Four-way Crossover, Single Dose Study to Investigate the Pharmacokinetics of LAS41008 120 mg Gastro-resistant Tablet and Fumaderm® 120 mg Gastro-resistant Tablet Under Fasting and Fed Conditions in Healthy Subjects [NCT02955693]Phase 132 participants (Actual)Interventional2016-09-30Completed
Claims Database Study of Utilization Patterns of Dimethyl Fumarate in Germany [NCT02969304]930 participants (Actual)Observational2016-12-30Completed
A Multi-center, Randomized, Double-blind, Three-arm, 16 Week, Adaptive Phase III Clinical Study to Investigate the Efficacy and Safety of LAS41008 vs LASW1835 and vs Placebo in Patients With Moderate to Severe Chronic Plaque Psoriasis [NCT01726933]Phase 3839 participants (Actual)Interventional2012-11-30Completed
Restoring Glutathione Synthesis With Tecfidera: An in Vivo H-MRS Single-Arm Study at 7T in Patients With Relapsing-Remitting Multiple Sclerosis [NCT02218879]7 participants (Actual)Observational2014-08-31Terminated
An Observational Study Utilising Data From Big MS Data Registries to Evaluate the Long-Term Safety of Vumerity and Tecfidera [NCT05767736]10,500 participants (Anticipated)Observational2024-02-29Not yet recruiting
An Open-Label, Randomised, Phase IV Study, to Assess the Efficacy and Safety of Tildrakizumab in Patients With Moderate-to-Severe Chronic Plaque Psoriasis Who Are Non-Responders to Dimethyl Fumarate Therapy (TRANSITION) [NCT04263610]Phase 4190 participants (Actual)Interventional2019-09-04Completed
Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme [NCT02337426]Phase 112 participants (Actual)Interventional2015-02-13Completed
A Randomised, Double Blind, Double Dummy, Active Comparator and Placebo Controlled Confirmative Non-inferiority Trial of FP187 Compared to Fumaderm® in Moderate to Severe Plaque Psoriasis [NCT01815723]Phase 30 participants (Actual)Interventional2016-06-30Withdrawn
A Multicenter, Double- Blind, Placebo- Controlled Study of Montelukast on Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera® (Dimethyl Fumarate) Delayed Release Capsules [NCT02410278]Phase 4102 participants (Actual)Interventional2015-03-12Completed
Open-Label, Multicenter, Multiple-Dose Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With Relapsing-Remitting Multiple Sclerosis Aged 10 to 17 Years [NCT02410200]Phase 222 participants (Actual)Interventional2015-09-30Completed
Phase IIA Study on Therapy With the NF-κB Inhibiting and Apoptosis Inducing Drug Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL) [NCT02546440]Phase 225 participants (Actual)Interventional2015-09-30Completed
[NCT02419638]0 participants (Actual)Observational2015-05-31Withdrawn(stopped due to Collaborative decision between study PI and sponsor.)
A Multicenter, Open-label Phase IV Study to Evaluate Whether a Medication Event Monitoring System (MEMS®) Can Improve Adherence to Tecfidera® (Delayed-release Dimethyl Fumarate) Treatment in Multiple Sclerosis Patients. [NCT02343159]Phase 484 participants (Actual)Interventional2015-02-28Terminated(stopped due to Sponsor Decision)
A Multicenter Extension Study to Determine the Long-Term Safety and Efficacy of BG00012 in Pediatric Subjects With Relapsing-Remitting Multiple Sclerosis [NCT02555215]Phase 320 participants (Actual)Interventional2016-02-22Completed
COMparison Between All immunoTherapies for Multiple Sclerosis. An Observational Long-term Prospective Cohort Study of Safety, Efficacy and Patient's Satisfaction of MS Disease Modulatory Treatments in Relapsing-remitting Multiple Sclerosis [NCT03193866]3,526 participants (Actual)Observational [Patient Registry]2017-06-02Active, not recruiting
Open-Label, Randomized, Multicenter, Multiple-Dose,Active-Controlled, Parallel-Group, Efficacy and Safety Study of BG00012 in Children From 10 to Less Than 18 Years of Age With Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension [NCT02283853]Phase 3156 participants (Actual)Interventional2014-08-28Active, not recruiting
A Multicenter, Global, Observational Study to Collect Information on Safety and to Document the Drug Utilization of Tecfidera™ (Dimethyl Fumarate) When Used in Routine Medical Practice in the Treatment of Multiple Sclerosis (ESTEEM) [NCT02047097]5,487 participants (Actual)Observational [Patient Registry]2013-11-19Completed
A Real Life, Non-interventional, Multicentre Study to Assess Resource Utilization and Quality of Life of Patients With Relapsing Forms of Multiple Sclerosis Treated With Dimethyl Fumarate in Greece - the FIDELITY Study [NCT03101735]455 participants (Actual)Observational2016-09-23Completed
An Open-Label, Parallel-Group, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BG00012 in Chinese, Japanese, and Caucasian Adult Healthy Volunteers [NCT01453426]Phase 171 participants (Actual)Interventional2012-01-31Completed
A Multicenter, Postmarketing Study of Dimethyl Fumarate (Tecfidera; BG00012) in Relapsing Forms of Multiple Sclerosis (RMS) Participants in China [NCT05658484]Phase 460 participants (Anticipated)Interventional2023-06-09Recruiting
A Multicenter, Open-Label, Single-Arm Study of Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera™ (Dimethyl Fumarate) Delayed-release Capsules [NCT01873417]Phase 4237 participants (Actual)Interventional2013-05-31Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of BG00012 in Subjects From the Asia-Pacific Region and Other Countries With Relapsing-Remitting Multiple Sclerosis [NCT01838668]Phase 3225 participants (Actual)Interventional2013-03-28Completed
An Open-Label Study to Assess the Effects of BG00012 on Lymphocyte Subsets in Subjects With Relapsing-Remitting Multiple Sclerosis [NCT02525874]Phase 3218 participants (Actual)Interventional2015-08-11Completed
Effects of Dimethyl Fumarate on Cognitive Performances and Gray Matter and Thalamic Pathology in Multiple Sclerosis: a Correlation Study. [NCT05811949]52 participants (Anticipated)Observational2021-02-24Recruiting
A Randomized, Double-Blind, Phase 3b Study to Evaluate Effects of Aspirin or Dose Titration on Flushing and Gastrointestinal Events Following Oral Administration of BG00012 Dosed at 240 mg BID [NCT01568112]Phase 3173 participants (Actual)Interventional2012-04-30Completed
A Retrospective, Multi-Center, Observational Study to Assess the Effect of Tecfidera® Delayed-Release Capsules on Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis (REALIZE) [NCT02519413]483 participants (Actual)Observational2015-07-31Completed
A Randomized, Double-Blind Study to Compare Gastrointestinal Tolerability Following Oral Administration of Bafiertam™ (Monomethyl Fumarate) or Tecfidera® (Dimethyl Fumarate) to Healthy Male and Female Volunteers [NCT04022473]Phase 1210 participants (Actual)Interventional2019-07-07Completed
A Multicenter, Open-Label, Single-Arm Study to Evaluate Gastrointestinal Tolerability in Subjects With Relapsing-Remitting Multiple Sclerosis Receiving Dimethyl Fumarate (TOLERATE) [NCT02125604]Phase 4214 participants (Actual)Interventional2014-06-30Completed
A Phase 4, Randomized, Double-Blind Study With a Safety Extension Period to Evaluate the Effect of Aspirin on Flushing Events in Subjects With Relapsing-Remitting Multiple Sclerosis Treated With Tecfidera® (Dimethyl Fumarate) Delayed-Release Capsules [NCT02090413]Phase 4241 participants (Actual)Interventional2014-05-31Completed
STATURE: A Prospective Observational Study of the relationShip beTween Oral DMT bURden and adhErence in People With MS [NCT04676204]323 participants (Anticipated)Observational2020-09-25Enrolling by invitation
A Multicenter, Treatment-Blind Phase 3b Study to Evaluate Whether 6-Week Up-Titration in Tecfidera® Dose is Effective in Reducing the Incidence of Gastrointestinal Adverse Events in Patients With Multiple Sclerosis [NCT02428231]Phase 362 participants (Actual)Interventional2015-04-30Terminated(stopped due to Sponsor decision)
A 24-week, Multicenter, Exploratory, Two Arm Study to Assess the Effect of Dimethyl Fumarate on Immune-Modulatory Action on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS) [NCT02461069]Phase 467 participants (Actual)Interventional2015-05-06Completed
An Open-Label Study to Assess the Immune Response to Vaccination in Tecfidera® (BG00012)-Treated Versus Interferon-Treated Subjects With Relapsing Forms of Multiple Sclerosis. [NCT02097849]Phase 271 participants (Actual)Interventional2015-02-28Completed
A Randomized, Placebo-Controlled, Parallel-Group Study in Pediatric Subjects Ages 10 Through 17 Years to Evaluate the Efficacy and Safety of BG00012 for the Treatment of Relapsing-Remitting Forms of Multiple Sclerosis [NCT02428218]Phase 30 participants (Actual)Interventional2016-05-31Withdrawn(stopped due to Feasibility)
A Randomized Clinical Trial of Dimethyl Fumarate as a Novel Therapeutic Agent for Obstructive Sleep Apnea [NCT02438137]Phase 265 participants (Actual)Interventional2015-05-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00420212 (6) [back to overview]Number of Subjects With Gadolinium (Gd)-Enhancing Lesions
NCT00420212 (6) [back to overview]Proportion of Subjects Relapsed
NCT00420212 (6) [back to overview]Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
NCT00420212 (6) [back to overview]Number of New or Newly Enlarging T2 Hyperintense Lesions
NCT00420212 (6) [back to overview]Number of Gadolinium-enhancing T1-weighted Lesions
NCT00420212 (6) [back to overview]Annualized Relapse Rate
NCT00451451 (5) [back to overview]Number of New T1 Hypointense Lesions
NCT00451451 (5) [back to overview]Number of New or Newly Enlarging T2 Hyperintense Lesions
NCT00451451 (5) [back to overview]Annualized Relapse Rate
NCT00451451 (5) [back to overview]Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
NCT00451451 (5) [back to overview]Proportion of Subjects Relapsed
NCT00835770 (16) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (AEs)
NCT00835770 (16) [back to overview]Percentage of Participants Who Had Relapses
NCT00835770 (16) [back to overview]Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384
NCT00835770 (16) [back to overview]Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384
NCT00835770 (16) [back to overview]Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384
NCT00835770 (16) [back to overview]Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384
NCT00835770 (16) [back to overview]Change From Baseline in Visual Function Test Scores at Week 384
NCT00835770 (16) [back to overview]Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Percent Change From Baseline in Brain Atrophy
NCT00835770 (16) [back to overview]Percent Change From Baseline in Magnetization Transfer Ratio (MTR)
NCT00835770 (16) [back to overview]Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
NCT00835770 (16) [back to overview]Annualized Relapse Rate (ARR)
NCT01156311 (8) [back to overview]Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy
NCT01156311 (8) [back to overview]Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average
NCT01156311 (8) [back to overview]Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average
NCT01156311 (8) [back to overview]Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy
NCT01156311 (8) [back to overview]Number of New or Newly Enlarging T2 Lesions
NCT01156311 (8) [back to overview]Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy
NCT01156311 (8) [back to overview]Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)
NCT01156311 (8) [back to overview]Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)
NCT01568112 (28) [back to overview]Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)
NCT01568112 (28) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)
NCT01568112 (28) [back to overview]Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results
NCT01568112 (28) [back to overview]Number of Participants With Abnormalities in Vital Signs
NCT01568112 (28) [back to overview]Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS
NCT01568112 (28) [back to overview]Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS
NCT01568112 (28) [back to overview]Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS
NCT01568112 (28) [back to overview]Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis
NCT01568112 (28) [back to overview]Clinical Laboratory Shifts From Baseline in Reported Values: Hematology
NCT01568112 (28) [back to overview]Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
NCT01568112 (28) [back to overview]Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
NCT01568112 (28) [back to overview]Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
NCT01568112 (28) [back to overview]Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)
NCT01568112 (28) [back to overview]Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS
NCT01568112 (28) [back to overview]Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS
NCT01568112 (28) [back to overview]Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS
NCT01568112 (28) [back to overview]Duration of Flushing Events During the Overall Treatment Period, Based on MFSS
NCT01568112 (28) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS
NCT01568112 (28) [back to overview]Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS
NCT01568112 (28) [back to overview]Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS
NCT01873417 (8) [back to overview]Summary of Use and Days on Symptomatic Therapy, by Category
NCT01873417 (8) [back to overview]Duration of GI-related Episodes in DMF-treated Participants
NCT01873417 (8) [back to overview]Participants' Use of Symptomatic Therapy, by Type and Category
NCT01873417 (8) [back to overview]Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy
NCT01873417 (8) [back to overview]Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale
NCT01873417 (8) [back to overview]Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS)
NCT01873417 (8) [back to overview]Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy
NCT01873417 (8) [back to overview]Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy
NCT02090413 (22) [back to overview]Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
NCT02090413 (22) [back to overview]Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Mental Component Summary (MCS)
NCT02090413 (22) [back to overview]Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48
NCT02090413 (22) [back to overview]Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS
NCT02090413 (22) [back to overview]Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS
NCT02090413 (22) [back to overview]Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
NCT02090413 (22) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
NCT02090413 (22) [back to overview]Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
NCT02090413 (22) [back to overview]Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
NCT02090413 (22) [back to overview]Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
NCT02090413 (22) [back to overview]Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Physical Component Summary (PCS)
NCT02090413 (22) [back to overview]Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) Questionnaire: Mobility
NCT02090413 (22) [back to overview]Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS
NCT02090413 (22) [back to overview]Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks
NCT02090413 (22) [back to overview]Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48
NCT02090413 (22) [back to overview]Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks
NCT02090413 (22) [back to overview]Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities
NCT02097849 (16) [back to overview]Number of Participants With Shifts From Baseline in Blood Chemistry
NCT02097849 (16) [back to overview]Number of Participants With Abnormalities in Vital Signs
NCT02097849 (16) [back to overview]Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs
NCT02097849 (16) [back to overview]Ratio of Serum Tetanus Level at Day 28 to Prevaccination
NCT02097849 (16) [back to overview]Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination
NCT02097849 (16) [back to overview]Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination
NCT02097849 (16) [back to overview]Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level
NCT02097849 (16) [back to overview]Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination
NCT02097849 (16) [back to overview]Number of Participants With Shifts From Baseline in Hematology
NCT02125604 (11) [back to overview]Percentage of Participants Who Discontinued Dimethyl Fumarate Due To Gastrointestinal-Related Treatment-Emergent Adverse Events
NCT02125604 (11) [back to overview]Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MAGISS
NCT02125604 (11) [back to overview]Worst Severity Of Gastrointestinal-Related Events In Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS
NCT02125604 (11) [back to overview]Percentage of Participants Who First Took Symptomatic Therapy for Gastrointestinal-Related Events at Weeks 4, 8, and 12
NCT02125604 (11) [back to overview]Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Overall Gastrointestinal Symptom Scale (MOGISS)
NCT02125604 (11) [back to overview]Number of Participants Who Utilized Symptomatic Therapy With Gastrointestinal-Related Events During the 12-Week Treatment Period: Modified Acute Gastrointestinal Symptom Scale (MAGISS)
NCT02125604 (11) [back to overview]Number of Participants Who Used Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category
NCT02125604 (11) [back to overview]Duration of Use of Symptomatic Therapies for Gastrointestinal-Related Events During the 12-Week Treatment Period, by Category
NCT02125604 (11) [back to overview]Duration of Gastrointestinal-Related Events in Participants Who Utilized Symptomatic Therapy During the 12-Week Treatment Period, MOGISS
NCT02125604 (11) [back to overview]Duration of Gastrointestinal-Related Events in Participants Who Utilize Symptomatic Therapy During the 12-Week Treatment Period, MAGISS
NCT02125604 (11) [back to overview]Percentage of Participants Who Required Dimethyl Fumarate Dose Reduction In Response To Gastrointestinal-Related Events
NCT02410200 (8) [back to overview]Maximum Observed Plasma Concentration (Cmax)
NCT02410200 (8) [back to overview]Apparent Clearance (CL/F)
NCT02410200 (8) [back to overview]Apparent Volume of Distribution (V/F)
NCT02410200 (8) [back to overview]Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)
NCT02410200 (8) [back to overview]Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period
NCT02410200 (8) [back to overview]Half-Life Lambda z
NCT02410200 (8) [back to overview]Time to Reach Maximum Observed Plasma Concentration (Tmax)
NCT02410200 (8) [back to overview]Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT02410278 (10) [back to overview]Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10
NCT02410278 (10) [back to overview]Average Change From Baseline in GSRS Overall Score at Day 1 to Week 10
NCT02410278 (10) [back to overview]Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10
NCT02410278 (10) [back to overview]Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8
NCT02410278 (10) [back to overview]Time to First Worsening From Baseline in GSRS Overall Score at Day 1 to Day 10
NCT02410278 (10) [back to overview]Percentage of Participants Who Required GI Symptomatic Therapy During the Study
NCT02410278 (10) [back to overview]Percentage of Participants Who Experienced AEs Related to Flushing
NCT02410278 (10) [back to overview]Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment
NCT02410278 (10) [back to overview]Percentage of Participants Who Discontinued DMF Therapy Due to GI-Related Adverse Events (AEs) From Day 0 to Week 10
NCT02410278 (10) [back to overview]Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8
NCT02438137 (2) [back to overview]Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values)
NCT02438137 (2) [back to overview]Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Very Late Antigen-4 (VLA-4/Lymphocyte Function-Associated Antigen-1 (LFA-1) Antigen
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK)
NCT02525874 (10) [back to overview]Change From Baseline in Immunoglobulin G (IgG) Subclasses up to 48 Weeks
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Myeloid and Natural Killer (NK) Cells
NCT02525874 (10) [back to overview]Change From Baseline in Immunoglobulin G (IgG) up to 48 Weeks
NCT02525874 (10) [back to overview]Change From Baseline in Immunoglobulin A (IgA) up to 48 Weeks
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cells Subsets
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cell Cytokines
NCT02525874 (10) [back to overview]Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: B-Cell Subsets
NCT02525874 (10) [back to overview]Change From Baseline in Immunoglobulin M (IgM) up to 48 Weeks
NCT02555215 (8) [back to overview]Number of Participants Experiencing Disability Progression
NCT02555215 (8) [back to overview]Percentage of Participants Experiencing One or More Relapses
NCT02555215 (8) [back to overview]Change From Baseline in the Degree of Disability
NCT02555215 (8) [back to overview]Total Number of New or Newly Enlarging T2 Hyperintense Lesions From Week 16 to Week 24
NCT02555215 (8) [back to overview]Total Number of New or Newly Enlarging T2 Hyperintense Lesions From Week 64 to Week 72
NCT02555215 (8) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT02555215 (8) [back to overview]Average Annualized Relapse Rate (ARR)
NCT02555215 (8) [back to overview]Number of Participants Discontinuing Treatment Due to an Adverse Event
NCT02739542 (6) [back to overview]The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)
NCT02739542 (6) [back to overview]Number of Newly Enlarging T2 Lesions
NCT02739542 (6) [back to overview]Number of New T2 Lesions
NCT02739542 (6) [back to overview]Number of Contrast Enhancing Lesions
NCT02739542 (6) [back to overview]Newly Enlarging T2 Lesions and New T2 Lesions Combined
NCT02739542 (6) [back to overview]Change in Lesion Volume on T2-weighted MRI
NCT02784834 (1) [back to overview]Incidence of Dose Limiting Toxicity
NCT02975349 (24) [back to overview]Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
NCT02975349 (24) [back to overview]Annualized Relapse Rate (ARR)
NCT02975349 (24) [back to overview]Annualized Relapse Rate (ARR) at Week 24
NCT02975349 (24) [back to overview]Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
NCT02975349 (24) [back to overview]Total Number of New or Enlarging T2 Lesions
NCT02975349 (24) [back to overview]Total Number of New Gadolinium-positive (Gd+) T1 Lesions
NCT02975349 (24) [back to overview]Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
NCT02975349 (24) [back to overview]Qualified Relapse-Free Status at Week 24
NCT02975349 (24) [back to overview]Qualified Relapse-free Status
NCT02975349 (24) [back to overview]Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
NCT02975349 (24) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
NCT02975349 (24) [back to overview]Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
NCT02975349 (24) [back to overview]Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
NCT02975349 (24) [back to overview]Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
NCT02975349 (24) [back to overview]Change From Baseline in Absolute B Cells (Active Treatment Period)
NCT02975349 (24) [back to overview]Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
NCT02975349 (24) [back to overview]Absolute Numbers of B Cells (Active Treatment Period)
NCT02975349 (24) [back to overview]Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
NCT02975349 (24) [back to overview]Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
NCT02975349 (24) [back to overview]Change From Week 24 in Volume of T2 Lesions at Week 48
NCT02975349 (24) [back to overview]Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
NCT02975349 (24) [back to overview]Total Number of Gadolinium-Enhancing T1 Lesions
NCT02975349 (24) [back to overview]Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
NCT02975349 (24) [back to overview]Change From Baseline in Volume of T2 Lesions at Week 24
NCT02981082 (1) [back to overview]6 Minute Walk Distance (6MWD)
NCT03093324 (9) [back to overview]Number of Participants With Adverse Events (AEs)
NCT03093324 (9) [back to overview]Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B
NCT03093324 (9) [back to overview]Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B
NCT03093324 (9) [back to overview]Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B
NCT03093324 (9) [back to overview]Number of Days With a Global GI Symptom and Impact Scale (GGISIS) Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B
NCT03093324 (9) [back to overview]Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B
NCT03093324 (9) [back to overview]Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B
NCT03093324 (9) [back to overview]Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B
NCT03093324 (9) [back to overview]Number of Days With Any Individual Gastrointestinal Symptom and Impact Scale (IGISIS) Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B
NCT03255382 (82) [back to overview]HADS Total Score-Depression: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]Hospital Anxiety & Depression Scale (HADS) Total Score-Anxiety: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Nail Psoriasis Severity Index (NAPSI): Change From Baseline to Week 16
NCT03255382 (82) [back to overview]NAPPA-CLIN Total Score: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]NAPSI: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]Participants With Baseline NAPSI ˃0: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Participants With Baseline NAPSI ˃0: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]PASI: Change From Baseline to Week 12
NCT03255382 (82) [back to overview]Palmoplantar Psoriasis Severity Index (PPASI): Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Body Surface Area (BSA) Affected by Psoriasis: Change From Baseline to Week 4
NCT03255382 (82) [back to overview]BSA Affected by Psoriasis: Change From Baseline to Week 12
NCT03255382 (82) [back to overview]BSA Affected by Psoriasis: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]BSA Affected by Psoriasis: Change From Baseline to Week 20
NCT03255382 (82) [back to overview]BSA Affected by Psoriasis: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]BSA Affected by Psoriasis: Change From Baseline to Week 8
NCT03255382 (82) [back to overview]Clinical Severity of Nail Psoriasis (NAPPA-CLIN) Total Score: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]DLQI Total Score: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]DLQI: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]EQ-5D-5L Total Score: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]EQ-5D-5L VAS: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]EQ-5D-5L Visual Analog Scale (VAS): Change From Baseline to Week 16
NCT03255382 (82) [back to overview]European Quality of Life 5 Dimensions (EQ-5D-5L) Total Score: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Summary of PBI at Week 24
NCT03255382 (82) [back to overview]Summary of Patient Benefit Index (PBI) at Week 16
NCT03255382 (82) [back to overview]Short Form Health Survey 36, Version 2 (SF-36 V2) Physical Component Summary (PCS) Score: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]SF-36 V2 PCS Score: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]SF-36 V2 Mental Component Summary (MCS) Score: Change From Baseline: to Week 16
NCT03255382 (82) [back to overview]SF-36 V2 MCS Score: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]PtGA: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]PSSI: Change From Baseline at Week 24
NCT03255382 (82) [back to overview]PSS Total Score: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]PSS Total Score: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Psoriasis Scalp Severity Index (PSSI): Change From Baseline at Week 16
NCT03255382 (82) [back to overview]Psoriasis Area and Severity Index (PASI): Change From Baseline to Week 4
NCT03255382 (82) [back to overview]PPASI: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]Percentage of Participants With PSS Score of 0 at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants With Psoriasis Symptoms Scale (PSS) Score of 0 at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 20
NCT03255382 (82) [back to overview]HADS Total Score-Anxiety: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 20
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear at Week 12
NCT03255382 (82) [back to overview]Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI90) at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 20
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 12
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 12
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 20
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 12
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 8
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 4
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 24
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 20
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 12
NCT03255382 (82) [back to overview]Patient's Global Assessment (PtGA): Change From Baseline to Week 16
NCT03255382 (82) [back to overview]PASI: Change From Baseline to Week 8
NCT03255382 (82) [back to overview]PASI: Change From Baseline to Week 24
NCT03255382 (82) [back to overview]PASI: Change From Baseline to Week 20
NCT03255382 (82) [back to overview]PASI: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]HADS Total Score-Depression: Change From Baseline to Week 16
NCT03255382 (82) [back to overview]Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 20
NCT03870763 (5) [back to overview]Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96
NCT03870763 (5) [back to overview]Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96
NCT03870763 (5) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT03870763 (5) [back to overview]Annualized Relapse Rate
NCT03870763 (5) [back to overview]Time to First Relapse
NCT04570670 (2) [back to overview]The Bioequivalent (BE) Comparison of AUC0-inf of Monomethyl Fumarate (MMF) Between Treatments
NCT04570670 (2) [back to overview]The BE Comparison of Cmax of Monomethyl Fumarate (MMF) Between Treatments

Number of Subjects With Gadolinium (Gd)-Enhancing Lesions

"Note: This outcome measure represents the categorical analysis for the previously listed secondary outcome measure Number of Gadolinium-enhancing T1-weighted lesions" (NCT00420212)
Timeframe: 2 years

,,
InterventionNumber of subjects (Number)
0 lesions1 lesion2 lesions3-4 lesions>=5 lesions
BG00012 240 mg 3 Times Daily (TID)13010237
BG00012 240 mg Twice Daily (BID)1428101
Placebo10316131518

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Proportion of Subjects Relapsed

A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurolgic evaluation committee. The proportion of subjects with a relapse was estimated using the Kaplan-Meier method, which was based on the time-to-first-relapse survival distribution. (NCT00420212)
Timeframe: 2 years

InterventionProportion of subjects,confirmed relapse (Number)
Placebo0.461
BG00012 240 mg Twice Daily (BID)0.270
BG00012 240 mg 3 Times Daily (TID)0.260

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Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)

The EDSS is based on a standardized neurological examination and focuses on symptoms that commonly occur in MS. EDSS scores range from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as ≥ 1.0 point increase in subjects with a baseline EDSS of ≥1.0, or a ≥1.5 point increase in subjects with a baseline EDSS = 0, and required that the increase from baseline was confirmed ≥12 weeks later. The proportion of subjects with confirmed (12-week) disability progression was estimated using the Kaplan-Meier method, which was based on the time-to-first-progression survival distribution. (NCT00420212)
Timeframe: 2 years

InterventionProportion of participants (Number)
Placebo0.271
BG00012 240 mg BID0.164
BG00012 240 mg TID0.177

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Number of New or Newly Enlarging T2 Hyperintense Lesions

The number of new or newly enlarging T2 hyperintense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T2 lesion count were calculated from a negative binomial regression model adjusted for region and baselineT2 lesion volume (NCT00420212)
Timeframe: 2 years

InterventionNumber of lesions (Mean)
Placebo17.0
BG00012 240 mg BID2.6
BG00012 240 mg TID4.4

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Number of Gadolinium-enhancing T1-weighted Lesions

The number of Gd-enhancing lesions was assessed using brain MRI scans following administration of gadolinium, a contrast agent. The mean number of Gd-enhancing lesions at 2 years was the average of the number of lesions at 2 years in a treatment group. (NCT00420212)
Timeframe: 2 years

InterventionNumber of lesions (Mean)
Placebo1.8
BG00012 240 mg BID0.1
BG00012 240 mg TID0.5

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Annualized Relapse Rate

A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurologic evaluation committee. The adjusted annualized relapse rate was calculated from a negative binomial regression model, adjusted for baseline EDSS (≤ 2.0 vs. >2.0), age (<40 versus ≥40 years), region, and the number of relapses in the 1 year prior to enrollment. (NCT00420212)
Timeframe: 2 years

InterventionRelapses per year (Mean)
Placebo0.364
BG00012 240 mg BID0.172
BG00012 240 mg TID0.189

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Number of New T1 Hypointense Lesions

The number of new T1 hypointense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T1 hypointense lesion count were calculated from a negative binomial regression model adjusted for region and baseline T1 hypointense lesion volume. (NCT00451451)
Timeframe: 2 years

InterventionNumber of lesions (Mean)
Placebo7.0
BG00012 240 mg Twice Daily (BID)3.0
BG00012 240 mg 3 Times Daily (TID)2.4
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)4.1

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Number of New or Newly Enlarging T2 Hyperintense Lesions

The number of new or newly enlarging T2 hyperintense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T2 hyperintense lesion count were calculated from a negative binomial regression model adjusted for region and baseline T2 hyperintense lesion volume. (NCT00451451)
Timeframe: 2 years

InterventionNumber of lesions (Mean)
Placebo17.4
BG00012 240 mg Twice Daily (BID)5.1
BG00012 240 mg 3 Times Daily (TID)4.7
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)8.0

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Annualized Relapse Rate

"A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurologic evaluation committee.~The adjusted annualized relapse rate was calculated from a negative binomial regression model , adjusted for baseline Expanded Disability Status Scale (EDSS ) score(≤2.0 versus>2.0), age (<40 versus ≥40 years), region, and the number of relapses in the 1 year prior to enrollment." (NCT00451451)
Timeframe: 2 years

InterventionRelapses Per Year (Mean)
Placebo0.401
BG00012 240 mg Twice Daily (BID)0.224
BG00012 240 mg 3 Times Daily (TID)0.198
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)0.286

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Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)

EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Scores range from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as ≥ 1.0 point increase in subjects with a baseline EDSS of ≥1.0, or ≥1.5 point increase in subjects with a baseline EDSS=0, and required that the increase from baseline was confirmed ≥ 12weeks later. The proportion of subjects with confirmed (12-week) disability progression was estimated using the Kaplan-Meier method, which was based on the time-to-first-progression survival distribution (NCT00451451)
Timeframe: 2 years

InterventionProportion of Participants (Number)
Placebo0.169
BG00012 240 mg Twice Daily (BID)0.128
BG00012 240 mg 3 Times Daily (TID)0.130
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)0.156

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Proportion of Subjects Relapsed

A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurologic evaluation committee. The proportion of subjects with a relapse was estimated using the Kaplan-Meier method, which was based on the time-to-first-relapse survival distribution. (NCT00451451)
Timeframe: 2 years

InterventionProportion of subjects,confirmed relapse (Number)
Placebo0.410
BG00012 240 mg Twice Daily (BID)0.291
BG00012 240 mg 3 Times Daily (TID)0.241
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)0.321

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Number of Participants With Treatment-Emergent Adverse Events (AEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. (NCT00835770)
Timeframe: Day 1 up to Week 561

InterventionParticipants (Count of Participants)
BG00012 240 mg BID824
BG00012 240 mg TID814

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Percentage of Participants Who Had Relapses

Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours. (NCT00835770)
Timeframe: Day 1 up to Week 384

Interventionpercentage of participants (Number)
BG00012 240 mg BID (Prior BG00012 240 mg BID)40
BG00012 240 mg TID (Prior BG00012 240 mg TID)41
BG00012 240 mg BID (Prior BG00012 Matched Placebo)34
BG00012 240 mg TID (Prior BG00012 Matched Placebo)36
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])31
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])31

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Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384

"The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. The EQ-5D provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has (1) no problems, (2) some problems, or (3) severe problems. A positive change from baseline indicates improvement." (NCT00835770)
Timeframe: Baseline, Week 384

,,,,,
Interventionscore on a scale (Mean)
BaselineChange at Week 384
BG00012 240 mg BID (Prior BG00012 240 mg BID)0.730.01
BG00012 240 mg BID (Prior BG00012 Matched Placebo)0.72-0.07
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])0.71-0.04
BG00012 240 mg TID (Prior BG00012 240 mg TID)0.730.00
BG00012 240 mg TID (Prior BG00012 Matched Placebo)0.710.00
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])0.72-0.03

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Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384

"The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. In EQ-VAS participants are asked to rate their current health on a 20 centimeter (cm) scale from 0 to 100 where 0 represents worst imaginable health state and 100 represents best imaginable health state. A positive change from baseline indicates improvement." (NCT00835770)
Timeframe: Baseline, Week 384

,,,,,
Interventionscore on a scale (Mean)
BaselineChange at Week 384
BG00012 240 mg BID (Prior BG00012 240 mg BID)70.97-0.48
BG00012 240 mg BID (Prior BG00012 Matched Placebo)70.40-7.24
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])66.80-1.71
BG00012 240 mg TID (Prior BG00012 240 mg TID)70.48-1.67
BG00012 240 mg TID (Prior BG00012 Matched Placebo)69.44-3.17
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])69.07-4.11

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Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384

The SF-36 is a brief (36-item) scale reflecting the impact of both dysfunctions and general health perception the questionnaire measures: 1.physical function (PF),2. role physical (RF),3. bodily pain (BP),4. role emotional (RE),5. social function (SF), 6. general health (GH),7. vitality (VT), 8. mental health (MH). Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. The questions related to each dimension are scored on a scale from 0 (worst score) to 100 (best score), with higher scores indicating better function. (NCT00835770)
Timeframe: Baseline, Week 384

,,,,,
Interventionscore on a scale (Mean)
Baseline: Physical Functioning ScoreChange at Week 384: Physical Functioning ScoreBaseline: Role-Physical ScoreChange at Week 384: Role-Physical ScoreBaseline: Bodily-Pain ScoreChange at Week 384: Bodily-Pain ScoreBaseline: General Health ScoreChange at Week 384: General Health ScoreBaseline: Vitality ScoreChange at Week 384: Vitality ScoreBaseline: Social Functioning ScoreChange at Week 384: Social Functioning ScoreBaseline: Role-Emotional ScoreChange at Week 384: Role-Emotional ScoreBaseline: Mental Health ScoreChange at Week 384: Mental Health ScoreBaseline: Mental Component ScoreChange at Week 384: Mental Component ScoreBaseline: Physical Component ScoreChange at Week 384: Physical Component Score
BG00012 240 mg BID (Prior BG00012 240 mg BID)68.480.7356.463.2069.681.3253.990.8750.481.1171.46-2.1664.870.4365.011.3245.400.0543.530.55
BG00012 240 mg BID (Prior BG00012 Matched Placebo)69.67-7.3756.35-10.0068.51-2.9254.45-2.2850.63-4.6769.67-5.6962.86-12.2265.42-3.9145.13-2.5543.74-2.29
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])69.10-6.1955.26-12.2169.30-3.6051.21-5.6451.30-6.7169.02-10.7660.29-13.1862.30-0.2944.00-2.5943.68-2.70
BG00012 240 mg TID (Prior BG00012 240 mg TID)71.78-4.7958.42-2.7570.42-1.4755.44-2.1252.21-0.7371.53-3.3065.570.4766.242.3145.630.8744.44-1.94
BG00012 240 mg TID (Prior BG00012 Matched Placebo)67.97-6.8959.87-8.2469.44-4.3652.42-0.5250.640.4072.23-2.0862.614.1765.152.3345.311.9743.56-3.25
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])68.20-6.2553.57-1.0468.59-4.4652.581.2150.331.0369.53-0.5264.26-3.5563.61-2.0645.030.0843.15-1.59

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Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384

EDSS scale ranges from 0 (Normal neurological exam, no disability) to 10 (Death) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. Sustained disability progression was defined as at least a 1.0 point increase on the EDSS from a baseline EDSS ≥1.0 that was sustained for at least 24 weeks, or a 1.5 point increase on the EDSS from a baseline EDSS =0 that was sustained for at least 24 weeks. (NCT00835770)
Timeframe: Baseline, Week 384

,,,,,
Interventionscore on a scale (Mean)
BaselineChange at Week 384
BG00012 240 mg BID (Prior BG00012 240 mg BID)2.440.28
BG00012 240 mg BID (Prior BG00012 Matched Placebo)2.500.37
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])2.570.39
BG00012 240 mg TID (Prior BG00012 240 mg TID)2.430.26
BG00012 240 mg TID (Prior BG00012 Matched Placebo)2.540.53
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])2.680.49

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Change From Baseline in Visual Function Test Scores at Week 384

Participants were tested using the contrast level of 100%, 2.5%, and 1.25% charts, and the scores were defined as the number of letters identified correctly for each chart (the maximum score was 60). Higher scores indicate better functioning. A positive change from baseline indicates better functioning. (NCT00835770)
Timeframe: Baseline, Week 384

,,,,,
Interventionscore on a scale (Mean)
Baseline: 100% ChartChange at Week 384: 100% ChartBaseline: 2.5% ChartChange at Week 384: 2.5% ChartBaseline: 1.25% ChartChange at Week 384: 1.25% Chart
BG00012 240 mg BID (Prior BG00012 240 mg BID)54.7-0.432.4-2.424.1-5.8
BG00012 240 mg BID (Prior BG00012 Matched Placebo)55.1-1.432.4-1.523.8-4.1
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])54.3-1.631.8-4.023.4-6.7
BG00012 240 mg TID (Prior BG00012 240 mg TID)55.0-1.932.6-3.324.2-6.0
BG00012 240 mg TID (Prior BG00012 Matched Placebo)54.8-1.232.3-4.923.7-7.4
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])55.0-0.731.7-2.122.2-5.0

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Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)

The Gd-enhancing lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionlesions (Mean)
Week 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)0.40.40.30.40.50.2
BG00012 240 mg BID (Prior BG00012 Matched Placebo)0.20.10.20.50.20.1
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])0.50.60.50.20.20.0
BG00012 240 mg TID (Prior BG00012 240 mg TID)0.40.40.40.50.50.5
BG00012 240 mg TID (Prior BG00012 Matched Placebo)0.30.20.10.30.20.7
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])0.40.30.30.60.30.3

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Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)

The T2 lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionlesions (Mean)
Week 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)1.63.44.25.87.48.2
BG00012 240 mg BID (Prior BG00012 Matched Placebo)2.73.84.05.68.27.5
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])3.44.95.75.56.88.9
BG00012 240 mg TID (Prior BG00012 240 mg TID)2.24.15.27.59.512.4
BG00012 240 mg TID (Prior BG00012 Matched Placebo)2.42.94.35.67.710.4
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])2.13.45.25.67.56.0

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Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)

The T1 hypointense lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionlesions (Mean)
Week 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)0.81.72.02.93.42.7
BG00012 240 mg BID (Prior BG00012 Matched Placebo)1.81.82.02.94.04.5
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])2.03.03.13.34.01.0
BG00012 240 mg TID (Prior BG00012 240 mg TID)1.01.92.83.44.85.9
BG00012 240 mg TID (Prior BG00012 Matched Placebo)1.72.12.63.84.93.6
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])1.31.92.93.04.25.6

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Percent Change From Baseline in Brain Atrophy

Brain atrophy was measured using magnetic resonance imaging (MRI) technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionpercent change (Mean)
Change at Week 48Change at Week 96Change at Week 144Change at Week 192Change at Week 240Change at Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)-1.206-1.372-1.708-2.138-2.313-2.216
BG00012 240 mg BID (Prior BG00012 Matched Placebo)-1.487-1.589-2.139-2.230-2.271-2.470
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])-1.496-1.883-2.386-2.645-2.249-2.657
BG00012 240 mg TID (Prior BG00012 240 mg TID)-1.263-1.500-1.876-2.117-2.253-2.271
BG00012 240 mg TID (Prior BG00012 Matched Placebo)-1.320-1.775-2.353-2.476-2.593-2.849
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])-1.414-1.810-2.252-2.417-2.790-2.496

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Percent Change From Baseline in Magnetization Transfer Ratio (MTR)

Magnetization Transfer Ratio (MTR) was measured using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionpercent change (Mean)
Change at Week 48Change at Week 96Change at Week 144Change at Week 192Change at Week 240Change at Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)-0.325-0.427-0.0421.038-0.0020.002
BG00012 240 mg BID (Prior BG00012 Matched Placebo)1.0341.6301.5253.0123.213-0.666
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])-0.081-4.269-4.4601.3842.959-0.466
BG00012 240 mg TID (Prior BG00012 240 mg TID)-0.383-0.5320.5090.9551.647-0.391
BG00012 240 mg TID (Prior BG00012 Matched Placebo)-0.567-0.9471.4113.1034.108-0.622
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])-0.3340.2153.1193.8410.673-1.114

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Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)

The Gd-enhancing lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionmillimeter cube (mm^3) (Mean)
BaselineWeek 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)31.759.649.144.139.196.818.2
BG00012 240 mg BID (Prior BG00012 Matched Placebo)96.018.827.718.845.821.77.9
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])37.142.564.342.612.017.50.0
BG00012 240 mg TID (Prior BG00012 240 mg TID)48.670.056.147.054.569.353.1
BG00012 240 mg TID (Prior BG00012 Matched Placebo)142.525.313.33.819.914.1230.2
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])41.742.722.392.955.117.134.1

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Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)

The T2 lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionmm^3 (Mean)
BaselineWeek 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)10231.99951.910331.39930.19837.710611.29611.8
BG00012 240 mg BID (Prior BG00012 Matched Placebo)8883.78992.18645.28829.49077.69711.18819.8
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])12628.911160.711318.110188.510421.911009.911586.3
BG00012 240 mg TID (Prior BG00012 240 mg TID)10408.39849.610434.010280.710760.011087.59800.8
BG00012 240 mg TID (Prior BG00012 Matched Placebo)10806.310114.59985.79792.310576.310591.410537.6
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])13044.412979.013974.112949.711671.512254.410404.8

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Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)

The T1 hypointense lesions was evaluated using MRI technique. (NCT00835770)
Timeframe: Baseline up to Week 288

,,,,,
Interventionmm^3 (Mean)
BaselineWeek 48Week 96Week 144Week 192Week 240Week 288
BG00012 240 mg BID (Prior BG00012 240 mg BID)3640.13829.53841.23767.43834.94038.63603.3
BG00012 240 mg BID (Prior BG00012 Matched Placebo)2754.22891.92921.03145.63385.43406.43350.6
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])3204.33271.03510.43499.23592.03503.43264.9
BG00012 240 mg TID (Prior BG00012 240 mg TID)3447.33715.53853.74074.04177.44238.23973.1
BG00012 240 mg TID (Prior BG00012 Matched Placebo)3623.13936.03849.44006.94330.03823.94187.5
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])3572.63743.33949.74126.14089.34057.72959.1

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Annualized Relapse Rate (ARR)

The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of participant-years followed in the period. (NCT00835770)
Timeframe: Day 1 up to Week 384

Interventionrelapses per participant-years (Number)
BG00012 240 mg BID (Prior BG00012 240 mg BID)0.159
BG00012 240 mg TID (Prior BG00012 240 mg TID)0.179
BG00012 240 mg BID (Prior BG00012 Matched Placebo)0.200
BG00012 240 mg TID (Prior BG00012 Matched Placebo)0.199
BG00012 240 mg BID (Prior Glatiramer Acetate [GA])0.184
BG00012 240 mg TID (Prior Glatiramer Acetate [GA])0.212

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Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy

Percentage of participants with post-baseline values for selected urinalysis parameters requiring further evaluation. For urine microscopy, results were categorized for male and female participants. For males, normal/negative was considered 0 to 3 red blood cells/high-power field (rbc/hpf), and positive was categorized in the following stages: 4 to 10, 11 to 20, 21 to 149, and ≥ 150 rbc/hpf. For females, normal/negative was considered 0 to 8 rbc/hpf, and positive was categorized in the following stages: 9 to 20, 21 to 30, 31 to 149, and ≥ 150 rbc/hpf. (NCT01156311)
Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

,
Interventionpercentage of participants (Number)
Urine blood: normal/negative; n=57, 47Urine blood: trace; n=57, 47Urine blood: 1+; n=57, 47Urine blood: 2+; n=57, 47Urine blood: 3+; n=57, 47Urine protein: normal/negative; n=57, 47Urine protein: trace; n=57, 47Urine protein: 1+; n=57, 47Urine protein: 2+; n=57, 47Urine protein: 3+; n=57, 47Urine protein: 4+; n=57, 47Urine glucose: normal/negative; n=57, 47Urine glucose: trace; n=57, 47Urine glucose: 1+; n=57, 47Urine glucose: 2+; n=57, 47Urine glucose: 3+; n=57, 47Urine glucose: 4+; n=57, 47Urine ketone: normal/negative; n=57, 47Urine ketone: trace; n=57, 47Urine ketone: 1+; n=57, 47Urine ketone: 2+; n=57, 47Urine ketone: 3+; n=57, 47Urine ketone: 4+; n=57, 47Urine microscopy (male): 0-3 rbc/hpf; n=9, 16Urine microscopy (male): 4-10 rbc/hpf; n=9, 16Urine microscopy (male): 11-20 rbc/hpf; n=9, 16Urine microscopy (male): 21-149 rbc/hpf; n=9, 16Urine microscopy (male): ≥ 150 rbc/hpf; n=9, 16Urine microscopy (female): 0-8 rbc/hpf; n=25, 28Urine microscopy (female): 9-20 rbc/hpf; n=25, 28Urine microscopy (female): 21-30 rbc/hpf; n=25, 28Urine microscopy (female): 31-149 rbc/hpf;n=25, 28Urine microscopy (female): ≥150 rbc/hpf; n=25, 28
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)6491511238451520094024005711284007561360864074
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)757575393526000932202247926114410000007684012

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Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average

The average is calculated as (total number of lesions in non-missing scans / number of non-missing magnetic resonance imaging [MRI] scans). (NCT01156311)
Timeframe: Week -8 through Week 24

,
Interventionlesions (Mean)
Average number of lesions from Weeks -8, -4, 0Average number of lesions from Weeks 16, 20, 24Change from average of Weeks -8, -4, 0
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)1.720.83-0.89
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)1.060.17-0.90

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Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average

The average is calculated as (total number of lesions in non-missing scans / number of non-missing MRI scans). (NCT01156311)
Timeframe: Week -4 through Week 24

,
Interventionlesions (Mean)
Average number of lesions from Weeks -4, 0Average number of lesions from Weeks 20, 24Change from average of Weeks -4, 0
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)0.790.18-0.62
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)0.910.06-0.84

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Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy

Percentage of participants with post-baseline liver enzyme values above the upper limit of normal (ULN). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and bilirubin. Elevated ALT/AST (ALT/AST ≥ 3*ULN) concurrent with elevated total bilirubin was also evaluated. (NCT01156311)
Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

,
Interventionpercentage of participants (Number)
ALT ≤ 1*ULNALT > 1*ULNALT ≥ 3*ULNALT > 5*ULNALT > 10*ULNALT > 20*ULNAST ≤ 1*ULNAST > 1*ULNAST ≥ 3*ULNAST > 5*ULNAST > 10*ULNAST > 20*ULNGGT ≤ 1*ULNGGT > 1*ULNGGT ≥ 3*ULNGGT > 5*ULNGGT > 10*ULNGGT > 20*ULNTotal Bilirubin ≤ 1*ULNTotal Bilirubin > 1*ULNTotal Bilirubin > 1.5*ULNTotal Bilirubin > 2*ULNALT/AST ≥ 3*ULN + Total Bilirubin > 1.5*ULNALT/AST ≥ 3*ULN + Total Bilirubin > 2*ULN
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)4753200064360000851500009464200
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)4753520068322000722842009820000

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Number of New or Newly Enlarging T2 Lesions

The number of new T2 lesions divided by the number of months since the reference visit during the Monotherapy Period and the Add-On Therapy Period. (NCT01156311)
Timeframe: Week -8 to Week 24

,
Interventionlesions per month (Mean)
New lesions in the Monotherapy PeriodNew lesions in the Add-on Therapy Period
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)0.890.25
Interferon Beta 1a (IFNß) and BG00012 (Dimethyl Fumarate)1.230.67

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Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy

Percentage of participants with potentially clinically significant hematology laboratory abnormalities. (NCT01156311)
Timeframe: collected from the start of BG00012 administration through to Week 26 +/- 5 days

,
Interventionpercentage of participants (Number)
White Blood Cells (total) < 3.0*10^9/LWhite Blood Cells (total) ≥ 16*10^9/LLymphocytes < 0.8*10^9/LLymphocytes < 0.5*10^9/LLymphocytes > 12*10^9/LNeutrophils ≤ 1.0*10^9/LNeutrophils < 1.5*10^9/LNeutrophils ≥ 12*10^9/LRed Blood Cells ≤ 3.3*10^12/LRed Blood Cells ≥ 6.8*10^12/LHemoglobin g/L ≤ 100Platelet Count ≤ 100*10^9/LPlatelet Count ≥ 600*10^9/L
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)2264002400000
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)923270013200000

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Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)

Percentage of participants with AEs, serious AEs (SAEs), and discontinuations due to AEs. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. An SAE was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. AEs were categorized as mild, moderate, or severe. All AEs occurring from enrollment to the day before BG00012 dosing are included. (NCT01156311)
Timeframe: from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0)

,
Interventionpercentage of participants (Number)
Participants with an AEParticipants with a moderate or severe AEParticipants with a severe AEParticipants with an SAEParticipants withdrawing from study due to an AE
Monotherapy Period: GA4927000
Monotherapy Period: IFNß5622300

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Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)

An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. TEAE was defined as having an onset date that was on or after the start of study treatment (BG00012), or that worsened after the start of study treatment. (NCT01156311)
Timeframe: AEs were collected from enrollment until the final study visit (Week 26 +/-5 days).

,
Interventionpercentage of participants (Number)
Participants with a TEAEParticipants with a moderate or severe TEAEParticipants with a severe TEAEParticipants with a related TEAEParticipants with a serious TEAEParticipants discontinuing BG00012 due to a TEAEParticipants withdrawing from study due to a TEAE
Glatiramer Acetate (GA) and BG00012 (Dimethyl Fumarate)10070158721717
Interferon Beta (IFNß) and BG00012 (Dimethyl Fumarate)9572147441414

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Worst Severity Scores of Acute GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS

Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. (NCT01568112)
Timeframe: Day 1 to Week 4

,,,
Interventionunits on a scale (Mean)
NauseaDiarrheaUpper abdominal painLower abdominal painVomitingIndigestionConstipationBloatingFlatulence
BG000121.61.81.11.40.30.90.91.11.3
BG00012 + ASA1.61.51.71.30.30.60.61.31.4
BG00012 Slow Titration1.51.01.41.20.20.90.91.01.6
Placebo0.71.00.80.50.20.70.40.51.3

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Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 (Combined), as Assessed by MFSS

Participant-reported flushing side effect events during Weeks 1 to 4 recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT01568112)
Timeframe: Week 5 to Week 8

,,,
Interventionpercentage of participants (Number)
Overall flushing eventsOverall redness eventsOverall warmth eventsOverall tingling eventsOverall itching events
BG000128678868178
BG00012 + ASA7264756458
BG00012 Slow Titration8579827061
Placebo2415171522

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Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 (Combined), as Assessed by MFSS

Participant-reported flushing side effect events during Weeks 1 to 4 recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT01568112)
Timeframe: Week 1 to Week 4

,,,
Interventionpercentage of participants (Number)
Overall flushing eventsOverall redness eventsOverall warmth eventsOverall tingling eventsOverall itching events
BG000128681888477
BG00012 + ASA7263675156
BG00012 Slow Titration9888958395
Placebo4125412316

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Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Flushing Severity Scale (MFSS)

Participant-reported flushing side effect events during the treatment period recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionpercentage of participants (Number)
Overall flushing eventsOverall redness eventsOverall warmth eventsOverall tingling eventsOverall itching events
BG000129186938886
BG00012 + ASA8177846772
BG00012 Slow Titration9890988698
Placebo4127412320

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Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious AEs (SAEs)

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes. An AE was considered treatment-emergent if it occurred after the start of study treatment or was present prior to the start of study treatment but subsequently worsened. (NCT01568112)
Timeframe: Day 1 up to end of Safety Follow-up (9 weeks)

,,,
Interventionparticipants (Number)
Any eventModerate or severe eventSevere eventRelated eventSerious eventDiscontinuation of treatment due to an eventWithdrawal from study due to an event
BG000122413417144
BG00012 + ASA2612416066
BG00012 Slow Titration2611118033
Placebo241008022

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Number of Participants With Shifts From Baseline in Electrocardiogram (ECG) Results

Shift to 'abnormal, not adverse event' includes unknown or normal to 'abnormal, not adverse event.' Shift to 'abnormal, adverse event' includes unknown or normal to 'abnormal, adverse event.' (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionparticipants (Number)
Shift to abnormal, not adverse eventShift to abnormal, adverse event
BG0001230
BG00012 + ASA20
BG00012 Slow Titration40
Placebo20

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Number of Participants With Abnormalities in Vital Signs

↑=increase; ↓=decrease; BL=baseline; bpm=beats per minute; SBP=systolic blood pressure; DBP=diastolic blood pressure; b/m=breaths per minute (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionparticipants (Number)
Temperature >38°C + ↑ from BL of ≥1°CPulse >120 bpm or ↑ from BL of >20 bpmPulse <50 bpm or ↓ from BL of >20 bpmSBP >180 mm Hg or ↑ from BL of >40 mm HgSBP <90 mm Hg or ↓ from BL of >30 mm HgDBP >105 mm Hg or ↑ from BL of >30 mm HgDBP <50 mm Hg or ↓ from BL of >20 mm HgRespiration rate >25 b/m or ↑ from BL of ≥50%Respiration rate 10 b/m or ↓ from BL of ≥50%
BG000120104020320
BG00012 + ASA0203010030
BG00012 Slow Titration0174010130
Placebo0811110110

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Duration of Acute GI Episodes During Weeks 5 to 8 (Combined), Based on MAGISS

Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects. (NCT01568112)
Timeframe: Week 5 to Week 8

,,,
Interventionhours (Mean)
Nausea; n=4, 9, 6, 9Diarrhea; n=12, 13, 6, 8Upper abdominal pain; n=6, 5, 5, 5Lower abdominal pain; n=7, 5, 5, 9Vomiting; n=1, 1, 1, 0Indigestion; n=6, 7, 7, 5Constipation; n=5, 2, 4, 4Bloating; n=7, 8, 7, 8Flatulence; n=9, 13, 7, 10
BG000124.346.621.123.9819.002.5715.4718.527.21
BG00012 + ASA2.667.051.862.840.585.0221.304.16105.86
BG00012 Slow Titration2.342.141.7322.54NA1.6318.2485.6418.48
Placebo3.964.505.296.639.002.4323.3512.4944.67

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Duration of Acute GI Episodes During Weeks 1 to 4 (Combined), Based on MAGISS

Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects. (NCT01568112)
Timeframe: Week 1 to Week 4

,,,
Interventionhours (Mean)
Nausea; n=10, 18, 18, 20Diarrhea; n=13, 20, 14, 14Upper abdominal pain; n=14, 14, 17, 15Lower abdominal pain; n=9, 18, 14, 13Vomiting; n=2, 2, 2, 2Indigestion; n=11, 11, 9, 11Constipation; n=4, 8, 11, 11Bloating; n=9, 14, 19, 11Flatulence; n=21, 17, 22, 19
BG000127.232.536.8114.205.6329.0027.6113.819.34
BG00012 + ASA11.1816.0417.6512.512.533.9315.1211.0735.86
BG00012 Slow Titration2.864.974.316.300.755.0521.2895.6961.13
Placebo10.475.2021.375.404.315.0817.056.7012.83

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Duration of Acute GI Episodes During the Overall Treatment Period, Based on MAGISS

Duration is calculated as follows: [(GI side effect) end date/time - (GI side effect) start date/time]/3600. For GI side effects with no end date, the end date is imputed using the last diary date/time. For subjects with more than 1 GI episode during a visit interval, the average duration for the study visit interval is used. The average duration is calculated as the total duration of the GI side effect / the total number of GI side effects. (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionhours (Mean)
Nausea; n=12, 21, 21, 22Diarrhea; n=20, 20 17, 15Upper abdominal pain; n=17, 14, 19, 19Lower abdominal pain; n=12, 19, 17, 16Vomiting; n=3, 3, 3, 2Indigestion; n=12, 13, 12, 12Constipation; n=6, 8, 13, 11Bloating; n=14, 14, 21, 12Flatulence; n=23, 20, 22, 20
BG000127.052.926.6713.9310.0816.4928.2016.919.06
BG00012 + ASA10.0114.6615.8810.841.883.8014.269.6868.93
BG00012 Slow Titration2.984.973.837.750.754.9120.9077.2463.84
Placebo9.745.5719.086.655.874.7620.499.5016.41

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Clinical Laboratory Shifts From Baseline in Reported Values: Urinalysis

Number of participants with clinical laboratory shifts from baseline in urinalysis values.Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. Shift to positive includes negative to positive and unknown to positive. RBC=red blood cells, WBC=white blood cells. (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionparticipants (Number)
Specific gravity: shift to low; n=44, 43, 43, 42Specific gravity: shift to high; n=44, 42, 43, 42pH: shift to low; n=44, 43, 43, 42pH: shift to high; n=44, 43, 43, 42Blood: shift to positive; n=42, 39, 39, 42Color: shift to positive; n=41, 43, 41, 39Glucose: shift to positive; n=44, 43, 43, 41Ketones: shift to positive; n=44, 43, 43, 42Protein: shift to positive; n=44, 41, 43, 41Microscopic RBC; n=44, 40, 40, 41Microscopic WBC; n=43, 40, 41, 42
BG0001200006127149
BG00012 + ASA02001419113
BG00012 Slow Titration00002506123
Placebo00003201034

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Clinical Laboratory Shifts From Baseline in Reported Values: Hematology

Number of participants with clinical laboratory shifts from baseline in hematology values. Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. abs=absolute (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionparticipants (Number)
White blood cells: shift to low; n=43, 43, 43, 41White blood cells: shift to high; n=44, 43, 43, 42Neutrophils abs: shift to low; n=42, 42, 42, 41Neutrophils abs: shift to high; n=44, 43, 43, 42Lymphocytes abs: shift to low; n=43, 43, 43, 41Lymphocytes abs: shift to high; n=44, 43, 42, 42Monocytes abs: shift to low; n=44, 43, 43, 42Monocytes abs: shift to high; n=44, 43, 43, 42Eosinophils abs: shift to low; n=44, 43, 43, 42Eosinophils abs: shift to high; n=44, 43, 43, 42Basophils abs: shift to high; n=44, 43, 43, 42Red blood cells: shift to low; n=44, 43, 43, 40Red blood cells: shift to high; n=44, 43, 43, 42Hemoglobin: shift to low; n=43, 41, 43, 42Hemoglobin: shift to high; n=44, 43, 43, 42Hematocrit: shift to low; n=44, 43, 43, 42Hematocrit: shift to high; n=43, 43, 43, 42Platelets: shift to low; n=44, 43, 43, 42Platelets: shift to high; n=44, 41, 43, 42
BG000122060500005120302000
BG00012 + ASA0120200006100100001
BG00012 Slow Titration0021300006000000101
Placebo0030100000000100000

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Clinical Laboratory Shifts From Baseline in Reported Values: Blood Chemistry

Number of participants with clinical laboratory shifts from baseline in blood chemistry values. Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. ALP=alkaline phosphatase, ALT=alanine aminotransferase, AST=aspartate aminotransferase, GGT=gamma-glutamyl transferase, LDH=lactate dehydrogenase, BUN=blood urea nitrogen. (NCT01568112)
Timeframe: Day 1 to Week 8

,,,
Interventionparticipants (Number)
ALP: shift to high; n=44, 42, 43, 42ALT: shift to high; n=44, 42, 43, 42AST: shift to high; n=44, 43, 43, 41GGT: shift to high; n=44, 41, 43, 42LDH: shift to low; n=44, 43, 43, 42LDH: shift to high; n=44, 43, 43, 42Total bilirubin: shift to high; n=44, 42, 42, 40BUN: shift to low; n=44, 43, 43, 42BUN: shift to high; n=44, 43, 41, 42Creatinine: shift to low; n=44, 43, 43, 42Creatinine: shift to high; n=44, 43, 43, 42Uric Acid: shift to low; n=44, 43, 43, 42Uric Acid: shift to high; n=44, 43, 43, 42Sodium: shift to low; n=44, 43, 43, 42Sodium: shift to high; n=44, 43, 43, 42Potassium: shift to low: n=44, 43, 43, 42Potassium: shift to high: n=44, 42, 42, 41Chloride: shift to low; n=44, 43, 43, 42Chloride: shift to high; n=44, 43, 43, 42Bicarbonate: shift to low; n=44, 43, 43, 42Bicarbonate: shift to high; n=44, 43, 43, 42Calcium: shift to low; n=44, 42, 43, 42Calcium: shift to high; n=44, 43, 43, 42Glucose: shift to low; n=43, 43, 41, 41Glucose: shift to high; n=44, 43, 43, 42Magnesium: shift to low; n=44, 43, 43, 42Magnesium: shift to high; n=44, 43, 43, 42Phosphorus: shift to low; n=44, 43, 43, 41Phosphorus: shift to high; n=44, 43, 43, 42Albumin: shift to low; n=44, 43, 43, 42Albumin: shift to high; n=44, 43, 43, 42Direct bilirubin: shift to high; n=44, 43, 43, 40Total protein: shift to low; n=44, 41, 43, 41Total protein: shift to high; n=44, 43, 43, 42
BG000120230001001000000100100010001000000
BG00012 + ASA0542010010000010100101010000000010
BG00012 Slow Titration0210001010000000000000020100100000
Placebo0120001010000100110100031100000000

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Percentage of Participants Reporting Overall Flushing Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MGFSS

Participant-reported flushing events during Weeks 1 to 4 of treatment (combined), recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to events reported in the 24 hours after the first dose on Day 1. (NCT01568112)
Timeframe: Day 2 to Week 4

Interventionpercentage of participants (Number)
Placebo41
BG0001284
BG00012 + ASA62
BG00012 Slow Titration90

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Percentage of Participants Reporting Overall Flushing Events During the Overall Treatment Period, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)

Participant-reported flushing events during the overall treatment period, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to events reported in the 24 hours after the first dose on Day 1. (NCT01568112)
Timeframe: Day 2 to Week 8

Interventionpercentage of participants (Number)
Placebo43
BG0001286
BG00012 + ASA74
BG00012 Slow Titration93

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Percentage of Participants Reporting GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS

The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence. (NCT01568112)
Timeframe: Week 5 to Week 8

Interventionpercentage of participants (Number)
Placebo41
BG0001259
BG00012 + ASA53
BG00012 Slow Titration61

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Percentage of Participants Reporting GI Events During Weeks 5 to 8 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)

The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration. (NCT01568112)
Timeframe: Week 5 to Week 8

Interventionpercentage of participants (Number)
Placebo34
BG0001259
BG00012 + ASA50
BG00012 Slow Titration58

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Percentage of Participants Reporting GI Events During Weeks 1 to 4 of Treatment (Combined), as Assessed by MAGISS

The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence. (NCT01568112)
Timeframe: Day 1 to Week 4

Interventionpercentage of participants (Number)
Placebo66
BG0001281
BG00012 + ASA79
BG00012 Slow Titration79

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Percentage of Participants Reporting GI Events During Weeks 1 to 4 (Combined), as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)

The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration. (NCT01568112)
Timeframe: Week 1 to Week 4

Interventionpercentage of participants (Number)
Placebo57
BG0001265
BG00012 + ASA67
BG00012 Slow Titration71

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Percentage of Participants Reporting GI Events During the Overall Treatment Period, as Assessed by the Modified Overall Gastrointestinal Symptom Scale (MOGISS)

The MOGISS is a questionnaire about overall side effects related to the gastrointestinal system (including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence) during the 24 hours prior to each AM dose. Participants were to answer the questions at the same time each day, before the morning drug administration. (NCT01568112)
Timeframe: Day 1 to Week 8

Interventionpercentage of participants (Number)
Placebo59
BG0001270
BG00012 + ASA79
BG00012 Slow Titration79

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Percentage of Participants Reporting Gastrointestinal (GI) Events During the Overall Treatment Period, as Assessed by the Modified Acute Gastrointestinal Scale (MAGISS)

The MAGISS is a participant-reported questionnaire about side effects of the gastrointestinal system following drug administration, and is based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. A participant was considered having overall GI side effect if he/she had a score of >=1 for at least one of the GI side effects including nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating and flatulence. (NCT01568112)
Timeframe: Day 1 to Week 8

Interventionpercentage of participants (Number)
Placebo73
BG0001281
BG00012 + ASA81
BG00012 Slow Titration86

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Worst Severity Scores of Acute GI Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MAGISS

Severity of GI-related events using the MAGISS to measure GI symptoms (nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, indigestion, constipation, bloating, flatulence), based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. (NCT01568112)
Timeframe: Week 5 to Week 8

,,,
Interventionunits on a scale (Mean)
NauseaDiarrheaUpper abdominal painLower abdominal painVomitingIndigestionConstipationBloatingFlatulence
BG000120.91.40.50.40.10.50.10.71.2
BG00012 + ASA0.80.80.40.50.10.50.60.70.4
BG00012 Slow Titration0.90.70.60.90.00.40.30.80.9
Placebo0.41.00.60.60.20.40.40.50.8

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Duration of Flushing Events During the Weeks 5 to 8 (Combined), Based on MFSS

For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes. (NCT01568112)
Timeframe: Week 5 to Week 8

Interventionminutes (Mean)
Placebo113.2
BG0001255.7
BG00012 + ASA73.2
BG00012 Slow Titration56.0

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Duration of Flushing Events During the Weeks 1 to 4 (Combined), Based on MFSS

For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes. (NCT01568112)
Timeframe: Week 1 to Week 4

Interventionminutes (Mean)
Placebo117.6
BG0001267.6
BG00012 + ASA89.8
BG00012 Slow Titration69.2

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Duration of Flushing Events During the Overall Treatment Period, Based on MFSS

For participants with more than 1 flushing episode during a visit interval, the average duration for the visit interval was used. The average duration is calculated as: the total duration of all flushing episodes / the total number of flushing episodes. (NCT01568112)
Timeframe: Day 1 to Week 8

Interventionminutes (Mean)
Placebo98.4
BG0001263.2
BG00012 + ASA69.8
BG00012 Slow Titration68.9

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Percentage of Participants Reporting Overall Flushing Events During Weeks 5 to 8 of Treatment (Combined), as Assessed by MGFSS

Participant-reported flushing events during Weeks 5 to 8 of treatment (combined), recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score. (NCT01568112)
Timeframe: Week 5 to Week 8

Interventionpercentage of participants (Number)
Placebo24
BG0001286
BG00012 + ASA67
BG00012 Slow Titration85

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Worst Severity Scores of Overall Flushing During Weeks 5 to 8 of Treatment (Combined), as Assessed by MFSS

Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT01568112)
Timeframe: Week 5 to Week 8

,,,
Interventionunits on a scale (Mean)
Overall flushingRednessWarmthTinglingItching
BG000123.83.63.93.33.1
BG00012 + ASA3.32.93.12.32.3
BG00012 Slow Titration3.12.92.92.21.8
Placebo0.90.40.80.30.7

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Worst Severity Scores of Overall Flushing During Weeks 1 to 4 of Treatment (Combined), as Assessed by MFSS

Worst severity of participant-reported flushing events during Weeks 1-4 of treatment combined, recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT01568112)
Timeframe: Day 1 to Week 4

,,,
Interventionunits on a scale (Mean)
Overall flushingRednessWarmthTinglingItching
BG000124.43.84.03.43.2
BG00012 + ASA2.41.62.31.61.3
BG00012 Slow Titration5.65.15.24.04.3
Placebo1.20.71.20.50.5

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Summary of Use and Days on Symptomatic Therapy, by Category

The total duration (in days) of use of each symptomatic therapy by participants as a result of GI symptoms experienced by DMF-treated participants is presented. If a participant had multiple different therapies on the same day, the days on symptomatic therapy was calculated as 1 day in the 'All Therapies' category. (NCT01873417)
Timeframe: 12 Weeks

Interventiondays (Mean)
All therapies; n=128Antacid; n=57Antisecretory/antimicrobial; n=49Anti-acid production; n=43Anti-bloating/anti-constipation agent; n=33Anti-diarrheal (anti-peristaltic); n=32Anti-emetic (central); n=18Laxative, fiber/probiotic; n=10Laxative, hygroscopic/osmotic; n=10Laxative, prokinetic; n=7Analgesic (nonsteroidal antiinflammatory); n=5Anti-allergic; n=3Anti-emetic; n=3Analgesic; n=2No treatment type recorded; n=1
Dimethyl Fumarate10.45.96.39.05.93.92.95.03.71.64.612.09.74.51.0

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Participants' Use of Symptomatic Therapy, by Type and Category

The symptomatic therapies used by DMF-treated participants were self-reported by type and category. Each participant may have taken more than one symptomatic therapy type but was counted only once within each therapy category. Acetylsalicylic acid (ASA) is abbreviated in the table. (NCT01873417)
Timeframe: 12 Weeks

Interventionparticipants (Number)
Category: AntacidTherapy: Calcium carbonateTherapy: Magnesium (Mg) hydroxideTherapy: Aluminum (Al) hydroxideTherapy: Al hydroxide, Mg hydroxide, simethiconeTherapy: ASA, citric acid, sodium bicarbonateTherapy: Generic anatacidTherapy: NauzeneTherapy: SucralfateCategory: Antisecretory/antimicrobialTherapy: Bismuth subsalicylateCategory: Anti-acid productionTherapy: OmeprazoleTherapy: RanitidineTherapy: FamotidineTherapy: LansoprazoleTherapy: PantoprazoleTherapy: CimetidineCategory: Anti-bloating/anti-constipation agentTherapy: SimethiconeTherapy: DocusateTherapy: Alpha-galactosidaseTherapy: EnemaCategory: Antidiarrheal (anti-peristaltic)Therapy: LoperamideTherapy: DiphenoxylateTherapy: DicyclomineCategory: Anti-emetic (central)Therapy: OndansetronTherapy: PromethazineTherapy: DimenhydrinateTherapy: TetrahydrocannabinolCategory: Laxative, fiber/probioticTherapy: Generic laxativeTherapy: Psyllium fiberTherapy: CulturelleCategory: Laxative, hygroscopic/osmoticTherapy: Polyethylene glycolTherapy: Phosphorated carbohydrate solutionTherapy: SennosidesTherapy: OsmoticCategory: Laxative, prokineticTherapy: BisacodylCategory:Analgesic (nonsteroidal antiinflammatory)Therapy: IbuprofenTherapy: NaproxenTherapy: ASACategory: Anti-allergicTherapy: MontelukastTherapy: DiphenhydramineCategory: Anti-emetic (pro-kinetic)Therapy: MetoclopramideCategory: AnalgesicTherapy: AcetaminophenCategory: No treatment type recordedTherapy: Not available
Dimethyl Fumarate575041321114949431815141031332951132293218873110532104321775321321332211

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Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale

Severity of GI-related events in DMF-treated participants using the MAGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. (NCT01873417)
Timeframe: 12 Weeks

Interventionunits on a scale (Mean)
Dimethyl Fumarate4.7

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Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS)

Severity of GI-related events in DMF-treated participants using the MOGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms. (NCT01873417)
Timeframe: 12 Weeks

Interventionunits on a scale (Mean)
Dimethyl Fumarate4.8

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Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy

Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS. (NCT01873417)
Timeframe: 12 Weeks

Interventionpercentage of participants (Number)
Dimethyl Fumarate54.1

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Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS

Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score. (NCT02090413)
Timeframe: Day 2 to Week 4

Interventionunits on a scale (Mean)
DMF + ASA-Placebo BID4.36
DMF + ASA 75 mg QAM3.99
DMF + ASA 150 mg BID3.93

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Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Mental Component Summary (MCS)

SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning). (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 80, 80Change at Week 24; n=68, 63, 61Change at Week 48/ET; n=68, 65, 64
DMF + ASA 150 mg BID46.496-0.312-2.82
DMF + ASA 75 mg QAM45.048-0.893-2.081
DMF + ASA-Placebo BID47.413-0.139-0.976

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Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48

Participant-reported flushing events (which include redness, warmth, tingling, and/or itching of the skin) during Weeks 13 to 48 of treatment were recorded in the CRF. (NCT02090413)
Timeframe: Week 13 to Week 48

Interventionparticipants (Number)
DMF + ASA-Placebo BID36
DMF + ASA 75 mg QAM35
DMF + ASA 150 mg BID42

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Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS

Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Week 5 to Week 12

,,
Interventionunits on a scale (Mean)
Weeks 5-8 combined; n=71, 71, 70Weeks 9 to 12 combined; n=67, 62, 65
DMF + ASA 150 mg BID3.472.95
DMF + ASA 75 mg QAM2.832.81
DMF + ASA-Placebo BID3.002.43

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Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS

Worst severity of participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Week 5 to Week 12

,,
Interventionunits on a scale (Mean)
Overall Flushing, Weeks 5-8 combined; n=71, 70, 70Overall Flushing, Weeks 9-12 combined;n=68, 65, 65Redness, Weeks 5-8 combined; n=71, 70, 70Redness, Weeks 9-12 combined; n=68, 65, 65Warmth, Weeks 5-8 combined; n=71, 70, 70Warmth, Weeks 9-12 combined; n=68, 65, 65Tingling, Weeks 5-8 combined; n=71, 70, 70Tingling, Weeks 9-12 combined; n=68, 65, 65Itching, Weeks 5-8 combined; n=71, 70, 70Itching, Weeks 9-12 combined; n=68, 65, 65
DMF + ASA 150 mg BID3.573.453.513.43.493.452.792.542.642.17
DMF + ASA 75 mg QAM3.243.152.832.753.113.062.071.782.171.69
DMF + ASA-Placebo BID3.372.53.272.573.32.662.031.711.921.51

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Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS

Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Day 1 to Week 4

,,
Interventionunits on a scale (Mean)
Overall flushingRednessWarmthTinglingItching
DMF + ASA 150 mg BID4.784.344.93.33.23
DMF + ASA 75 mg QAM4.734.654.883.623.64
DMF + ASA-Placebo BID4.844.835.033.313.7

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Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS

Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Week 5 to Week 12

,,
Interventionpercentage of participants (Number)
Weeks 5-8 combined; n=71, 71, 70Weeks 9-12 combined; n=67, 62, 65
DMF + ASA 150 mg BID80.076.9
DMF + ASA 75 mg QAM73.267.7
DMF + ASA-Placebo BID74.661.2

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Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)

Participant-reported flushing events during the first 4 weeks treatment, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score. (NCT02090413)
Timeframe: Day 2 to Week 4

,,
Interventionpercentage of participants (Number)
Weeks 1-4 combined; n=80, 79, 80Week 1; n=80, 77, 80Week 2; n=77, 76, 79Week 3; n=74, 74, 76Week 4; n=72, 71, 71
DMF + ASA 150 mg BID88.883.869.653.954.9
DMF + ASA 75 mg QAM92.485.761.855.454.9
DMF + ASA-Placebo BID90.083.876.673.059.7

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Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)

Participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Day 1 to Week 4

,,
Interventionpercentage of participants (Number)
Overall flushing eventsOverall redness eventsOverall warmth eventsOverall tingling eventsOverall itching events
DMF + ASA 150 mg BID96.388.897.586.376.3
DMF + ASA 75 mg QAM96.288.597.487.279.5
DMF + ASA-Placebo BID91.390.092.581.387.5

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Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. (NCT02090413)
Timeframe: Week 13 to Week 48

,,
Interventionparticipants (Number)
Any eventModerate or severe eventSevere eventRelated eventSerious eventDiscontinued treatment due to eventDiscontinued study due to event
DMF + ASA 150 mg BID6651124931010
DMF + ASA 75 mg QAM68501242766
DMF + ASA-Placebo BID6640545399

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Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Physical Component Summary (PCS)

SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning). (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or early termination (ET)

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 80, 80Change at Week 24; n=68, 63, 61Change at Week 48/ET; n=68, 65, 64
DMF + ASA 150 mg BID43.16-1.471-2.989
DMF + ASA 75 mg QAM41.990.551-1.449
DMF + ASA-Placebo BID44.627-0.014-1.008

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Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS

Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). (NCT02090413)
Timeframe: Week 5 to Week 12

,,
Interventionpercentage of participants (Number)
Overall Flushing, Weeks 5-8 combined; n=71, 70, 70Overall Flushing, Weeks 9-12 combined;n=68, 65, 65Redness, Weeks 5-8 combined; n=71, 70, 70Redness, Weeks 9-12 combined; n=68, 65, 65Warmth, Weeks 5-8 combined; n=71, 70, 70Warmth, Weeks 9-12 combined; n=68, 65, 65Tingling, Weeks 5-8 combined; n=71, 70, 70Tingling, Weeks 9-12 combined; n=68, 65, 65Itching, Weeks 5-8 combined; n=71, 70, 70Itching, Weeks 9-12 combined; n=68, 65, 65
DMF + ASA 150 mg BID84.378.581.473.882.975.471.461.564.356.9
DMF + ASA 75 mg QAM82.969.275.761.580.070.855.749.264.352.3
DMF + ASA-Placebo BID80.366.277.570.680.370.657.754.454.948.5

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression

"EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 79, 80Change at Week 24; n=67, 63, 60Change at Week 48/ET; n=67, 63, 63
DMF + ASA 150 mg BID1.7630-0.032
DMF + ASA 75 mg QAM1.848-0.19-0.127
DMF + ASA-Placebo BID1.642-0.060.03

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort

"EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 79, 80Change at Week 24; n=67, 63, 60Change at Week 48/ET; n=67, 64, 63
DMF + ASA 150 mg BID1.9750.1-0.127
DMF + ASA 75 mg QAM2.03800.078
DMF + ASA-Placebo BID2-0.104-0.09

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care

"EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 79, 80Change at Week 24; n=67, 63, 60Change at Week 48/ET; n=67, 64, 63
DMF + ASA 150 mg BID1.3630.0170.079
DMF + ASA 75 mg QAM1.38-0.079-0.109
DMF + ASA-Placebo BID1.321-0.045-0.045

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS

"For the EQ-VAS, the participant was instructed to draw a line on a 20-cm vertical scale at the point that best describes his or her own health, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=80, 80, 80Change at Week 24; n=66, 63, 60Change at Week 48/ET; n=66, 64, 63
DMF + ASA 150 mg BID73.438-2.95-1.476
DMF + ASA 75 mg QAM69.6-0.587-0.438
DMF + ASA-Placebo BID78.288-2.318-3.061

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) Questionnaire: Mobility

"EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 79, 80Change at Week 24; n=67, 63, 60Change at Week 48/ET; n=67, 63, 63
DMF + ASA 150 mg BID1.888-0.050.095
DMF + ASA 75 mg QAM1.7850.0950.079
DMF + ASA-Placebo BID1.877-0.1040.03

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Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS

Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). For participants with more than 1 flushing event during a visit interval, the average duration for the visit interval was used. (NCT02090413)
Timeframe: Day 1 to Week 12

,,
Interventionhours (Mean)
Weeks 1-4 combined; n=73, 75, 77Weeks 5-8 combined; n=57, 58, 59Weeks 9-12 combined; n=45, 45, 51
DMF + ASA 150 mg BID1.111.080.79
DMF + ASA 75 mg QAM0.80.730.69
DMF + ASA-Placebo BID0.691.060.66

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Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks

A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin. (NCT02090413)
Timeframe: Day 1 to Week 12

,,
Interventionparticipants (Number)
Discontinuing treatmentDiscontinuing study
DMF + ASA 150 mg BID22
DMF + ASA 75 mg QAM00
DMF + ASA-Placebo BID00

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Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48

A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin. (NCT02090413)
Timeframe: Week 13 to Week 48

,,
Interventionparticipants (Number)
Discontinuing treatmentDiscontinuing study
DMF + ASA 150 mg BID00
DMF + ASA 75 mg QAM00
DMF + ASA-Placebo BID22

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Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. (NCT02090413)
Timeframe: Day 1 to Week 12

,,
Interventionparticipants (Number)
Any eventModerate or severe eventSevere eventRelated eventSerious eventDiscontinued treatment due to eventDiscontinued study due to event
DMF + ASA 150 mg BID632684021213
DMF + ASA 75 mg QAM6838538199
DMF + ASA-Placebo BID6624335155

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Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities

"EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). A negative change from Baseline indicates improvement." (NCT02090413)
Timeframe: Baseline, Week 24, Week 48 or ET

,,
Interventionunits on a scale (Mean)
Baseline; n=81, 79, 80Change at Week 24; n=67, 63, 60Change at Week 48/ET; n=67, 64, 63
DMF + ASA 150 mg BID2.025-0.0170.063
DMF + ASA 75 mg QAM1.9750-0.016
DMF + ASA-Placebo BID1.827-0.060.149

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Number of Participants With Shifts From Baseline in Blood Chemistry

Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. (NCT02097849)
Timeframe: Screening to Week 4

,
Interventionparticipants (Number)
Alanine Aminotransferase: Shift to Low; n=33, 38Alanine Aminotransferase: Shift to High; n=30, 35Aspartate Aminotransferase: Shift to Low; n=33, 37Aspartate Aminotransferase: Shift to High; n=33,36Total Bilirubin: Shift to Low; n=32, 37Total Bilirubin: Shift to High; n=33, 38Gamma-glutamyl Transferase: Shift to Low; n=33, 38Gamma-glutamyl Transferase: Shift to High; n=33,38Blood Urea Nitrogen: Shift to Low; n=33, 38Blood Urea Nitrogen: Shift to High; n=33, 38Creatinine: Shift to Low; n=33, 38Creatinine: Shift to High; n=33, 37Sodium: Shift to Low; n=33, 38Sodium: Shift to High; n=33, 38Potassium: Shift to Low; n=33, 38Potassium: Shift to High; n=33, 38Chloride: Shift to Low; n=33, 38Chloride: Shift to High; n=33, 38
Non-Pegylated IFN Treated Plus Vaccinations020100000100000010
Tecfidera Treated Plus Vaccinations010010000100000000

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Number of Participants With Abnormalities in Vital Signs

Temperature increase: > 38 celcius (C) or ≥ 1 C increase from baseline. Pulse increase: > 120 beats per minute (bpm) or > 20 bpm increase from baseline. Pulse decrease: < 50 bpm or > 20 bpm decrease from baseline. Systolic blood pressure (SBP) increase: > 180 millimeters of mercury (mmHg) or > 40 mmHg from baseline. SBP decrease: < 90 mmHg or > 30 mmHg decrease from baseline. Diastolic blood pressure (DBP) increase: > 105 mmHg or > 30 mmHg increase from baseline. DBP decrease: < 50 mmHg or > 20 mmHg decrease from baseline. (NCT02097849)
Timeframe: Screening to Week 4

,
Interventionparticipants (Number)
Temperature IncreasePulse IncreasePulse DecreaseSBP IncreaseSBP DecreaseDBP IncreaseDBP Decrease
Non-Pegylated IFN Treated Plus Vaccinations0101000
Tecfidera Treated Plus Vaccinations0100010

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Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above. (NCT02097849)
Timeframe: Day 1 to Week 4

,
Interventionparticipants (Number)
Any EventModerate or Severe EventSevere EventEvent Related to Existing TherapySerious EventSerious Event Related to Existing TherapySerious Event Related to Td VaccineSerious Event Related to PPSV23 VaccineSerious Event Related to MCV4 VaccineWithdrew From Study Due to an Event
Non-Pegylated IFN Treated Plus Vaccinations18923000000
Tecfidera Treated Plus Vaccinations16703000000

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Ratio of Serum Tetanus Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionratio (Median)
Non-Pegylated IFN Treated Plus Vaccinations6.128
Tecfidera Treated Plus Vaccinations4.463

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Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionratio (Median)
Non-Pegylated IFN Treated Plus Vaccinations27.000
Tecfidera Treated Plus Vaccinations13.845

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Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionratio (Median)
Non-Pegylated IFN Treated Plus Vaccinations9.667
Tecfidera Treated Plus Vaccinations4.741

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Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations61
Tecfidera Treated Plus Vaccinations42

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Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-tetanus serum immunoglobulin G (IgG) levels (responders) from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations73
Tecfidera Treated Plus Vaccinations68

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Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations85
Tecfidera Treated Plus Vaccinations82

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Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations88
Tecfidera Treated Plus Vaccinations95

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Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations70
Tecfidera Treated Plus Vaccinations47

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Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations79
Tecfidera Treated Plus Vaccinations66

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Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations38
Tecfidera Treated Plus Vaccinations37

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Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionpercentage of participants (Number)
Non-Pegylated IFN Treated Plus Vaccinations53
Tecfidera Treated Plus Vaccinations53

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Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination

Interventionratio (Median)
Non-Pegylated IFN Treated Plus Vaccinations3.300
Tecfidera Treated Plus Vaccinations3.408

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Number of Participants With Shifts From Baseline in Hematology

Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. (NCT02097849)
Timeframe: Screening to Week 4

,
Interventionparticipants (Number)
Hemoglobin: Shift to Low; n=28, 36Hemoglobin: Shift to High; n=32, 38Hematocrit: Shift to Low; n=31, 37Hematocrit: Shift to High; n=32, 38Red Blood Cell Count: Shift to Low; n=25, 32Red Blood Cell Count: Shift to High; n=33, 37White Blood Cell Count: Shift to Low; n=27, 30White Blood Cell Count: Shift to High; n=33, 38Neutrophils: Shift to Low; n=27, 34Neutrophils: Shift to High; n=33, 37Basophils: Shift to Low; n=33, 38Basophils: Shift to High; n=33, 38Monocytes: Shift to Low; n=33, 38Monocytes: Shift to High; n=33, 38Lymphocytes: Shift to Low; n=33, 22Lymphocytes: Shift to High; n=33, 38Eosinophils: Shift to Low; n=33, 38Eosinophils: Shift to High; n=33, 38Platelet Count: Shift to Low; n=31, 38Platelet Count: Shift to High; n=32, 37
Non-Pegylated IFN Treated Plus Vaccinations10201022320002400010
Tecfidera Treated Plus Vaccinations00104040200020100000

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Maximum Observed Plasma Concentration (Cmax)

(NCT02410200)
Timeframe: Day 8

Interventionng/mL (Mean)
BG000121998.62

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Apparent Clearance (CL/F)

(NCT02410200)
Timeframe: Day 8

InterventionL/h (Mean)
BG0001274.45

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Apparent Volume of Distribution (V/F)

(NCT02410200)
Timeframe: Day 8

InterventionL (Mean)
BG0001298.19

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Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)

(NCT02410200)
Timeframe: Day 8

Interventionh*mcg/mL (Mean)
BG000123630.52

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Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period

(NCT02410200)
Timeframe: Baseline Period (Week -8 to Day 0), On-Treatment Assessment Period (Week 16 to Week 24)

Interventionlesions (Mean)
BG00012-7.9

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Half-Life Lambda z

(NCT02410200)
Timeframe: Day 8

Interventionhours (Mean)
BG000120.84

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Time to Reach Maximum Observed Plasma Concentration (Tmax)

(NCT02410200)
Timeframe: Day 8

Interventionhours (Mean)
BG000124.20

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Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. (NCT02410200)
Timeframe: Up to Week 28

Interventionparticipants (Number)
Any eventModerate or severe eventSevere eventEvent related to BG00012Serious eventSerious event related to BG00012Discontinued treatment due to an eventWithdrew from study due to an event
BG000122071165022

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Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Worsening in severity was defined as a positive average change from baseline (Day 0) to Day 10 in the GSRS score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Average change is the sum of changes from baseline in GSRS score over the first 10 days divided by the total of days with a GSRS score. (NCT02410278)
Timeframe: Baseline (Day 0), Day 10 (10 days after Day 0)

Interventionpercentage of participants (Number)
MITT-Placebo17
MITT-Montelukast33

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Average Change From Baseline in GSRS Overall Score at Day 1 to Week 10

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and Week 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. (NCT02410278)
Timeframe: Baseline (Day 0), Day 1 (1 day after Day 0), Week 10 (10 weeks after Day 0)

,
Interventionunits on scale (Mean)
Day 0Change From Day 1 to Week 10
MITT-Montelukast0.84-0.31
MITT-Placebo0.80-0.37

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Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. (NCT02410278)
Timeframe: Baseline (Day 0), Day 1 (1 day after Day 0), Day 10 (10 days after Day 0)

,
Interventionunits on a scale (Mean)
Day 0Change From Day 1 to Day 10
MITT-Montelukast0.84-0.23
MITT-Placebo0.80-0.28

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Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Recovery was defined as a GSRS score less than or equal to the Day 0 score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Time to recovery was defined as the date of recovery minus the date of the last occurrence of the worst score. (NCT02410278)
Timeframe: Baseline (Day 0), Day 1 (1 Day after Day 0) to Week 8 (8 weeks after Day 0)

Interventiondays (Median)
MITT-Placebo1
MITT-Montelukast1

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Time to First Worsening From Baseline in GSRS Overall Score at Day 1 to Day 10

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose.. Time to the first worsening was defined as the number of days from Day 1 to the first date with a worsened GSRS score. Censoring occurred at Day 10. (NCT02410278)
Timeframe: Baseline (Day 0), Day 1 (1 day after Day 0) to Day 10 (10 days after Day 0)

Interventiondays (Median)
MITT-Placebo10
MITT-Montelukast7

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Percentage of Participants Who Required GI Symptomatic Therapy During the Study

Symptomatic therapies were not permitted during the first 10 days after starting montelukast or placebo. From Day 10 onward, participants were allowed to use the following symptomatic therapies to treat DMF-related GI events: bismuth subsalicylate, simethicone, calcium carbonate, loperamide, proton-pump inhibitors and ondansetron. (NCT02410278)
Timeframe: Day 10 to Week 10

Interventionpercentage of participants (Number)
MITT-Placebo33
MITT-Montelukast33

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Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 3. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 is the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. (NCT02410278)
Timeframe: Baseline (Day 0), Day 3 (72 hours after Day 0)

,
Interventionunits on scale (Mean)
Day 0Change from Day 0 to Day 3
MITT-Montelukast0.84-0.18
MITT-Placebo0.80-0.28

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Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8

The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and the specified time point. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. (NCT02410278)
Timeframe: Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0)

,
Interventionunit on scale (Mean)
Day 0Change from Day 1 to Week 1Change from Day 1 to Week 2Change from Day 1 to Week 3Change from Day 1 to Week 4Change from Day 1 to Week 5Change from Day 1 to Week 6Change from Day 1 to Week 7Change from Day 1 to Week 8
MITT-Montelukast0.84-0.21-0.25-0.26-0.26-0.28-0.29-0.30-0.31
MITT-Placebo0.80-0.30-0.29-0.31-0.33-0.35-0.35-0.36-0.36

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Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values)

Levels of markers in the blood known as cytokines (measured in picograms per milliliter) were measured on a monthly basis from Month 0 (baseline) to Month 4. The outcome is the mean difference in cytokine level from baseline to month 4 (mean level at Month 4 - mean level at Baseline). Values were log-transformed for normality, prior to analysis. (NCT02438137)
Timeframe: Month 0 to Month 4

,
Interventionpicograms/milliliter (log-transformed) (Mean)
Interleukin-6Tissue necrosis factor-alphaInterleukin-10Monocyte chemoattractant protein-1
Dimethyl Fumarate (Tecfidera®) Capsules0.038-0.0020.0840.005
Placebo-0.0150.003-0.0360.057

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Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)

For the 50 participants who had interpretable month 4 polysomnography (PSG) data available, mean change in sleep apnea severity, as measured by the mean change in respiratory disturbance index (RDI) between baseline (Month 0) PSG and Month 4 PSG, was calculated. The RDI represents the total number of apneas, hypopneas and respiratory-related arousals per hour of sleep. (NCT02438137)
Timeframe: Month 0 to Month 4

Interventionrespiratory events/hour (Mean)
Dimethyl Fumarate (Tecfidera®) Capsules-3.11
Placebo10.2

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Very Late Antigen-4 (VLA-4/Lymphocyte Function-Associated Antigen-1 (LFA-1) Antigen

VLA-4/LFA-1 antigen subsets include CD11a+ (% of B cells), CD11a+ (% of T cells), CD11a+ (% of MNC), CD11a+ (% of dendritic cells [CD11c++]), CD11a+ (% of lymphocytes), CD11a+ (% of monocytes), CD11a+ (% of neutrophils), CD49d+ (% of B cells), CD49d+ (% of T cells), CD49d+ (% of MNC), CD49d+ (% of dendritic cells [CD11c++]), CD49d+ (% of lymphocytes), CD49d+ (% of monocytes) and CD49d+ (% of neutrophils). (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells/mm^3 (Mean)
CD11a+ (% of B cells): BaselineCD11a+ (% of B cells): Change at Week 4CD11a+ (% of B cells): Change at Week 8CD11a+ (% of B cells): Change at Week 12CD11a+ (% of B cells): Change at Week 24CD11a+ (% of B cells): Change at Week 36CD11a+ (% of B cells): Change at Week 48CD11a+ (% of T cells): BaselineCD11a+ (% of T cells): Change at Week 4CD11a+ (% of T cells): Change at Week 8CD11a+ (% of T cells): Change at Week 12CD11a+ (% of T cells): Change at Week 24CD11a+ (% of T cells): Change at Week 36CD11a+ (% of T cells): Change at Week 48CD11a+ (% of MNC): BaselineCD11a+ (% of MNC): Change at Week 4CD11a+ (% of MNC): Change at Week 8CD11a+ (% of MNC): Change at Week 12CD11a+ (% of MNC): Change at Week 24CD11a+ (% of MNC): Change at Week 36CD11a+ (% of MNC): Change at Week 48CD11a+ (% of dendritic cells [CD11c++]): BaselineCD11a+ (% of dendritic cells [CD11c++]): CW 4CD11a+ (% of dendritic cells [CD11c++]): CW 8CD11a+ (% of dendritic cells [CD11c++]): CW 12CD11a+ (% of dendritic cells [CD11c++]): CW 24CD11a+ (% of dendritic cells [CD11c++]): CW 36CD11a+ (% of dendritic cells [CD11c++]): CW 48CD11a+ (% of lymphocytes): BaselineCD11a+ (% of lymphocytes): Change at Week 4CD11a+ (% of lymphocytes): Change at Week 8CD11a+ (% of lymphocytes): Change at Week 12CD11a+ (% of lymphocytes): Change at Week 24CD11a+ (% of lymphocytes): Change at Week 36CD11a+ (% of lymphocytes): Change at Week 48CD11a+ (% of monocytes): BaselineCD11a+ (% of monocytes): Change at Week 4CD11a+ (% of monocytes): Change at Week 8CD11a+ (% of monocytes): Change at Week 12CD11a+ (% of monocytes): Change at Week 24CD11a+ (% of monocytes): Change at Week 36CD11a+ (% of monocytes): Change at Week 48CD11a+ (% of neutrophils): BaselineCD11a+ (% of neutrophils): Change at Week 4CD11a+ (% of neutrophils): Change at Week 8CD11a+ (% of neutrophils): Change at Week 12CD11a+ (% of neutrophils): Change at Week 24CD11a+ (% of neutrophils): Change at Week 36CD11a+ (% of neutrophils): Change at Week 48CD49d+ (% of B cells): BaselineCD49d+ (% of B cells): Change at Week 4CD49d+ (% of B cells): Change at Week 8CD49d+ (% of B cells): Change at Week 12CD49d+ (% of B cells): Change at Week 24CD49d+ (% of B cells): Change at Week 36CD49d+ (% of B cells): Change at Week 48CD49d+ (% of T cells): BaselineCD49d+ (% of T cells): Change at Week 4CD49d+ (% of T cells): Change at Week 8CD49d+ (% of T cells): Change at Week 12CD49d+ (% of T cells): Change at Week 24CD49d+ (% of T cells): Change at Week 36CD49d+ (% of T cells): Change at Week 48CD49d+ (% of MNC): BaselineCD49d+ (% of MNC): Change at Week 4CD49d+ (% of MNC): Change at Week 8CD49d+ (% of MNC): Change at Week 12CD49d+ (% of MNC): Change at Week 24CD49d+ (% of MNC): Change at Week 36CD49d+ (% of MNC): Change at Week 48CD49d+ (% of dendritic cells [CD11c++]): BaselineCD49d+ (% of dendritic cells [CD11c++]): CW 4CD49d+ (% of dendritic cells [CD11c++]): CW 8CD49d+ (% of dendritic cells [CD11c++]): CW 12CD49d+ (% of dendritic cells [CD11c++]): CW 24CD49d+ (% of dendritic cells [CD11c++]): CW 36CD49d+ (% of dendritic cells [CD11c++]): CW 48CD49d+ (% of lymphocytes): BaselineCD49d+ (% of lymphocytes): Change at Week 4CD49d+ (% of lymphocytes): Change at Week 8CD49d+ (% of lymphocytes): Change at Week 12CD49d+ (% of lymphocytes): Change at Week 24CD49d+ (% of lymphocytes): Change at Week 36CD49d+ (% of lymphocytes): Change at Week 48CD49d+ (% of monocytes): BaselineCD49d+ (% of monocytes): Change at Week 4CD49d+ (% of monocytes): Change at Week 8CD49d+ (% of monocytes): Change at Week 12CD49d+ (% of monocytes): Change at Week 24CD49d+ (% of monocytes): Change at Week 36CD49d+ (% of monocytes): Change at Week 48CD49d+ (% of neutrophils): BaselineCD49d+ (% of neutrophils): Change at Week 4CD49d+ (% of neutrophils): Change at Week 8CD49d+ (% of neutrophils): Change at Week 12CD49d+ (% of neutrophils): Change at Week 24CD49d+ (% of neutrophils): Change at Week 36CD49d+ (% of neutrophils): Change at Week 48
Dimethyl Fumarate (BG00012)99.330.340.440.170.19-1.43-0.1499.900.050.070.060.02-1.29-0.5396.850.470.590.59-0.38-1.55-2.3199.810.040.020.100.01-1.27-0.8498.240.040.070.26-0.35-1.99-2.5698.000.290.920.77-0.40-0.36-1.5297.800.831.230.550.35-2.880.4299.87-0.500.000.01-0.01-0.07-0.0491.23-0.45-0.11-0.06-0.12-1.32-0.0286.790.230.380.85-0.07-0.46-1.2599.77-0.420.120.030.00-0.06-0.2391.29-0.310.030.440.01-0.75-1.1088.770.820.960.820.983.870.695.614.431.170.27-0.67-0.290.92

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T Cell, B Cell, Natural Killer Cell (TBNK)

Lymphocyte subsets include T cell, B cell and Natural killer (NK) cells. (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells per cubic millimeter (cells/mm^3) (Mean)
B Cells: BaselineB Cells: Change at Week 4B Cells: Change at Week 8B Cells: Change at Week 12B Cells: Change at Week 24B Cells: Change at Week 36B Cells: Change at Week 48NK Cells: BaselineNK Cells: Change at Week 4NK Cells: Change at Week 8NK Cells: Change at Week 12NK Cells: Change at Week 24NK Cells: Change at Week 36NK Cells: Change at Week 48T Cells: BaselineT Cells: Change at Week 4T Cells: Change at Week 8T Cells: Change at Week 12T Cells: Change at Week 24T Cells: Change at Week 36T Cells: Change at Week 48CD4+ T cells: BaselineCD4+ T cells: Change at Week 4CD4+ T cells: Change at Week 8CD4+ T cells: Change at Week 12CD4+ T cells: Change at Week 24CD4+ T cells: Change at Week 36CD4+ T cells: Change at Week 48CD8+ T cells: BaselineCD8+ T cells:Change at Week 4CD8+ T cells:Change at Week 8CD8+ T cells:Change at Week 12CD8+ T cells:Change at Week 24CD8+ T cells:Change at Week 36CD8+ T cells:Change at Week 48
Dimethyl Fumarate (BG00012)235.9-18.8-48.2-65.9-76.5-70.1-60.7184.26.1-9.0-21.7-26.9-41.5-42.01318.1-44.8-167.0-284.3-446.7-545.5-580.2879.0-27.4-95.4-176.8-269.8-329.7-352.6419.5-14.2-65.3-100.4-170.2-201.4-214.9

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Change From Baseline in Immunoglobulin G (IgG) Subclasses up to 48 Weeks

(NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventionmilligram per deciliter (Mean)
IgG Subclass 1: BaselineIgG Subclass 1: Change at Week 4IgG Subclass 1: Change at Week 8IgG Subclass 1: Change at Week 12IgG Subclass 1: Change at Week 24IgG Subclass 1: Change at Week 36IgG Subclass 1: Change at Week 48IgG Subclass 2: BaselineIgG Subclass 2: Change at Week 4IgG Subclass 2: Change at Week 8IgG Subclass 2: Change at Week 12IgG Subclass 2: Change at Week 24IgG Subclass 2: Change at Week 36IgG Subclass 2: Change at Week 48IgG Subclass 3: BaselineIgG Subclass 3: Change at Week 4IgG Subclass 3: Change at Week 8IgG Subclass 3: Change at Week 12IgG Subclass 3: Change at Week 24IgG Subclass 3: Change at Week 36IgG Subclass 3: Change at Week 48IgG Subclass 4: BaselineIgG Subclass 4: Change at Week 4IgG Subclass 4: Change at Week 8IgG Subclass 4: Change at Week 12IgG Subclass 4: Change at Week 24IgG Subclass 4: Change at Week 36IgG Subclass 4: Change at Week 48IgG Subclasses 1-4 Quant: BaselineIgG Subclasses 1-4 Quant: Change at Week 4IgG Subclasses 1-4 Quant: Change at Week 8IgG Subclasses 1-4 Quant: Change at Week 12IgG Subclasses 1-4 Quant: Change at Week 24IgG Subclasses 1-4 Quant: Change at Week 36IgG Subclasses 1-4 Quant: Change at Week 48
Dimethyl Fumarate (BG00012)542.9-29.2-28.5-14.8-3.0-23.1-0.5350.7-22.7-26.5-18.9-5.5-22.4-21.556.93-2.1-0.7-1.0-0.44.61.530.351.24-0.38-0.121.081.283.261029.9-54.6-41.9-28.5-55.7-70.3-65.1

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: Myeloid and Natural Killer (NK) Cells

Myeloid and natural killer cell subsets include CD56Bright NK cells, CD56Dim NK cells, Classical Monocytes, Myeloid dendritic cells, Non-classical Monocytes, Plasmacytoid dendritic cells, Total dendritic cells and Total monocytes [CD14+]. (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells/mm^3 (Mean)
CD56Bright NK cells: BaselineCD56Bright NK cells: Change at Week 4CD56Bright NK cells: Change at Week 8CD56Bright NK cells: Change at Week 12CD56Bright NK cells: Change at Week 24CD56Bright NK cells: Change at Week 36CD56Bright NK cells: Change at Week 48CD56Dim NK cells: BaselineCD56Dim NK cells: Change at Week 4CD56Dim NK cells: Change at Week 8CD56Dim NK cells: Change at Week 12CD56Dim NK cells: Change at Week 24CD56Dim NK cells: Change at Week 36CD56Dim NK cells: Change at Week 48Classical Monocytes: BaselineClassical Monocytes: Change at Week 4Classical Monocytes: Change at Week 8Classical Monocytes: Change at Week 12Classical Monocytes: Change at Week 24Classical Monocytes: Change at Week 36Classical Monocytes: Change at Week 48Myeloid dendritic cells: BaselineMyeloid dendritic cells: Change at Week 4Myeloid dendritic cells: Change at Week 8Myeloid dendritic cells: Change at Week 12Myeloid dendritic cells: Change at Week 24Myeloid dendritic cells: Change at Week 36Myeloid dendritic cells: Change at Week 48Non-classical Monocytes: BaselineNon-classical Monocytes: Change at Week 4Non-classical Monocytes: Change at Week 8Non-classical Monocytes: Change at Week 12Non-classical Monocytes: Change at Week 24Non-classical Monocytes: Change at Week 36Non-classical Monocytes: Change at Week 48Plasmacytoid dendritic cells: BaselinePlasmacytoid dendritic cells: Change at Week 4Plasmacytoid dendritic cells: Change at Week 8Plasmacytoid dendritic cells: Change at Week 12Plasmacytoid dendritic cells: Change at Week 24Plasmacytoid dendritic cells: Change at Week 36Plasmacytoid dendritic cells: Change at Week 48Total dendritic cells: BaselineTotal dendritic cells: Change at Week 4Total dendritic cells: Change at Week 8Total dendritic cells: Change at Week 12Total dendritic cells: Change at Week 24Total dendritic cells: Change at Week 36Total dendritic cells: Change at Week 48Total monocytes [CD14+]: BaselineTotal monocytes [CD14+]: Change at Week 4Total monocytes [CD14+]: Change at Week 8Total monocytes [CD14+]: Change at Week 12Total monocytes [CD14+]: Change at Week 24Total monocytes [CD14+]: Change at Week 36Total monocytes [CD14+]: Change at Week 48
Dimethyl Fumarate (BG00012)14.01.81.81.32.12.32.1192.9-2.0-17.2-31.4-50.7-61.1-68.5301.47.56.09.3-8.7-1.5-0.824.961.46-0.61-0.233.023.63-6.2032.02.2-1.9-10.8-6.9-10.6-9.26.520.000.30-0.86-0.69-0.80-2.2235.42.0-1.3-1.91.62.5-9.1374.626.912.614.4-19.3-21.7-19.2

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Change From Baseline in Immunoglobulin G (IgG) up to 48 Weeks

(NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventiong/L (Mean)
BaselineChange at Week 4Change at Week 8Change at Week 12Change at Week 24Change at Week 36Change at Week 48
Dimethyl Fumarate (BG00012)10.51-0.77-0.64-0.44-0.62-0.36-0.53

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Change From Baseline in Immunoglobulin A (IgA) up to 48 Weeks

(NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventionmilligram per liter (mg/L) (Mean)
BaselineChange at Week 4Change at Week 8Change at Week 12Change at Week 24Change at Week 36Change at Week 48
Dimethyl Fumarate (BG00012)2116.5-120.0-112.8-93.6-101.5-65.1-94.9

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cells Subsets

T-cells subsets includes Activated CD4+ T-cell, Activated CD8+ T-cell, Activated CD8+ T-cell [CD38+], Activated Th (T helper) 1 phenotype, Activated Th17 phenotype, Activated Th2-enriched phenotype, Activated CD4+ T-cell [CD38+HLA-DR+], Activated CD4+ T-cell [HLA-DR+], Activated CD8+ T-cell [HLA-DR+], Central Memory (CM) CD4+ T-cell [CD45RA-CCR7+], CM CD4+ T-cell [CD45RA-CCR7+], CM CD8+ T-cell [CD45RA-CCR7+], Effector CD4+ T-cell [CD45RA+CCR7-], Effector CD8+ T-cell [CD45RA+CCR7-], Effector Memory (EM) CD4+ T-cell [CD45RA-CCR7-], EM CD8+ T-cell [CD45RA-CCR7-], Effector Regulatory T-cells, Effector CD4+ T-cell [CD45RA+CCR7-], Effector CD8+ T-cell [CD45RA+CCR7-], Naïve CD4+ T-cell [CD45RA+], Naïve CD8+ T-cell [CD45RA+], Naïve (N) CD8+ T-cell [CD45RA+], Naïve Regulatory T-cells, Terminal Effector Regulatory T-cells, Th1 phenotype, Th17 phenotype, Th2-enriched phenotype. Here, Change at week is represented as CW. (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells/mm^3 (Mean)
Activated CD4+ T-cell [CD38+]: BaselineActivated CD4+ T-cell [CD38+]: Change at Week 4Activated CD4+ T-cell [CD38+]: Change at Week 8Activated CD4+ T-cell [CD38+]: Change at Week 12Activated CD4+ T-cell [CD38+]: Change at Week 24Activated CD4+ T-cell [CD38+]: Change at Week 36Activated CD4+ T-cell [CD38+]: Change at Week 48Activated CD8+ T-cell ([CD38+HLA-DR+]): BaselineActivatedCD8+T-cell(CD38+HLA-DR+):CW 4ActivatedCD8+T-cell(CD38+HLA-DR+):CW 8ActivatedCD8+T-cell(CD38+HLA-DR+):CW 12ActivatedCD8+T-cell(CD38+HLA-DR+):CW 24ActivatedCD8+T-cell(CD38+HLA-DR+):CW 36ActivatedCD8+T-cell(CD38+HLA-DR+):CW 48Activated CD8+ T-cell [CD38+]: BaselineActivated CD8+ T-cell [CD38+]: Change at Week 4Activated CD8+ T-cell [CD38+]: Change at Week 8Activated CD8+ T-cell [CD38+]: Change at Week 12Activated CD8+ T-cell [CD38+]: Change at Week 24Activated CD8+ T-cell [CD38+]: Change at Week 36Activated CD8+ T-cell [CD38+]: Change at Week 48Activated Th1 phenotype: BaselineActivated Th1 phenotype: Change at Week 4Activated Th1 phenotype: Change at Week 8Activated Th1 phenotype: Change at Week 12Activated Th1 phenotype: Change at Week 24Activated Th1 phenotype: Change at Week 36Activated Th1 phenotype: Change at Week 48Activated Th17 phenotype: BaselineActivated Th17 phenotype: Change at Week 4Activated Th17 phenotype: Change at Week 8Activated Th17 phenotype: Change at Week 12Activated Th17 phenotype: Change at Week 24Activated Th17 phenotype: Change at Week 36Activated Th17 phenotype: Change at Week 48Activated Th2-enriched phenotype: BaselineActivated Th2-enriched phenotype: Change at Week 4Activated Th2-enriched phenotype: Change at Week 8Activated Th2-enriched phenotype: CW 12Activated Th2-enriched phenotype: CW 24Activated Th2-enriched phenotype: CW 36Activated Th2-enriched phenotype: CW 48Activated CD4+ T-cell [CD38+HLA-DR+]: BaselineActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 4ActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 8ActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 12ActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 24ActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 36ActivatedCD4+ T-cell[CD38+HLA-DR+]:CW 48Activated CD4+ T-cell [HLA-DR+]: BaselineActivated CD4+ T-cell [HLA-DR+]: Change at Week 4Activated CD4+ T-cell [HLA-DR+]: Change at Week 8Activated CD4+ T-cell [HLA-DR+]: Change at Week 12Activated CD4+ T-cell [HLA-DR+]: Change at Week 24Activated CD4+ T-cell [HLA-DR+]: Change at Week 36Activated CD4+ T-cell [HLA-DR+]: Change at Week 48Activated CD8+ T-cell [HLA-DR+]: BaselineActivated CD8+ T-cell [HLA-DR+]: Change at Week 4Activated CD8+ T-cell [HLA-DR+]: Change at Week 8Activated CD8+ T-cell [HLA-DR+]: Change at Week 12Activated CD8+ T-cell [HLA-DR+]: Change at Week 24Activated CD8+ T-cell [HLA-DR+]: Change at Week 36Activated CD8+ T-cell [HLA-DR+]: Change at Week 48CM CD4+ T-cell [CD45RA-CCR7+]: BaselineCM CD4+ T-cell[CD45RA-CCR7+]:CW 4CM CD4+ T-cell[CD45RA-CCR7+]:CW 8CM CD4+T-cell[CD45RA-CCR7+]:CW 12CM CD4+T-cell[CD45RA-CCR7+]:CW 24CentralMemoryCD4+T-cell[CD45RA-CCR7+]:CW 36CM CD4+T-cell[CD45RA-CCR7+]:CW 48CM CD8+ T-cell [CD45RA-CCR7+]: BaselineCM CD8+T-cell[CD45RA-CCR7+]:CW 4CM CD8+T-cell[CD45RA-CCR7+]:CW 8CM CD8+T-cell[CD45RA-CCR7+]:CW 12CM CD8+T-cell[CD45RA-CCR7+]:CW 24CM CD8+T-cell[CD45RA-CCR7+]:CW 36CM CD8+T-cell[CD45RA-CCR7+]:CW 48Effector CD4+ T-cell [CD45RA+CCR7-]: BaselineEffector CD4+ T-cell[CD45RA+CCR7-]:Change atWeek4Effector CD4+ T-cell[CD45RA+CCR7-]:Change atWeek8Effector CD4+ T-cell[CD45RA+CCR7-]:Change atWeek12Effector CD4+ T-cell[CD45RA+CCR7-]:CW 24Effector CD4+ T-cell[CD45RA+CCR7-]:CW 36Effector CD4+ T-cell[CD45RA+CCR7-]:CW 48Effector CD8+ T-cell [CD45RA+CCR7-]: BaselineEffector CD8+ T-cell[CD45RA+CCR7-]:Change atWeek4Effector CD8+ T-cell[CD45RA+CCR7-]:Change atWeek8Effector CD8+ T-cell[CD45RA+CCR7-]:CW 12Effector CD8+ T-cell[CD45RA+CCR7-]:CW 24Effector CD8+ T-cell[CD45RA+CCR7-]:CW 36Effector CD8+ T-cell[CD45RA+CCR7-]:CW 48EM CD4+ T-cell [CD45RA-CCR7-]: BaselineEM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 4EM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 8EM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 12EM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 24EM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 36EM CD4+ T-cell [CD45RA-CCR7-]: Change at Week 48EM CD8+ T-cell [CD45RA-CCR7-]: BaselineEM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 4EM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 8EM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 12EM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 24EM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 36EM CD8+ T-cell [CD45RA-CCR7-]: Change at Week 48Effector Regulatory T-cells: BaselineEffector Regulatory T-cells: Change at Week 4Effector Regulatory T-cells: Change at Week 8Effector Regulatory T-cells: Change at Week 12Effector Regulatory T-cells: Change at Week 24Effector Regulatory T-cells: Change at Week 36Effector Regulatory T-cells: Change at Week 48Memory CD4+ T-cell [CD45RA-]: BaselineMemory CD4+ T-cell [CD45RA-]: Change at Week 4Memory CD4+ T-cell [CD45RA-]: Change at Week 8Memory CD4+ T-cell [CD45RA-]: Change at Week 12Memory CD4+ T-cell [CD45RA-]: Change at Week 24Memory CD4+ T-cell [CD45RA-]: Change at Week 36Memory CD4+ T-cell [CD45RA-]: Change at Week 48Memory CD8+ T-cell [CD45RA-]: BaselineMemory CD8+ T-cell [CD45RA-]: Change at Week 4Memory CD8+ T-cell [CD45RA-]: Change at Week 8Memory CD8+ T-cell [CD45RA-]: Change at Week 12Memory CD8+ T-cell [CD45RA-]: Change at Week 24Memory CD8+ T-cell [CD45RA-]: Change at Week 36Memory CD8+ T-cell [CD45RA-]: Change at Week 48Naïve CD4+ T-cell [CD45RA+CCR7+]: BaselineNaïve CD4+ T-cell [CD45RA+CCR7+]: Change at Week 4Naïve CD4+ T-cell [CD45RA+CCR7+]: Change at Week 8Naïve CD4+ T-cell[CD45RA+CCR7+]:Change at Week 12Naïve CD4+ T-cell[CD45RA+CCR7+]:Change at Week 24Naïve CD4+ T-cell[CD45RA+CCR7+]:Change at Week 36Naïve CD4+ T-cell[CD45RA+CCR7+]:Change at Week 48Naïve CD4+ T-cell [CD45RA+]: BaselineNaïve CD4+ T-cell [CD45RA+]: Change at Week 4Naïve CD4+ T-cell [CD45RA+]: Change at Week 8Naïve CD4+ T-cell [CD45RA+]: Change at Week 12Naïve CD4+ T-cell [CD45RA+]: Change at Week 24Naïve CD4+ T-cell [CD45RA+]: Change at Week 36Naïve CD4+ T-cell [CD45RA+]: Change at Week 48Naïve CD8+ T-cell [CD45RA+CCR7+]: BaselineNaïve CD8+ T-cell [CD45RA+CCR7+]: Change at Week 4Naïve CD8+ T-cell [CD45RA+CCR7+]: Change at Week 8Naïve CD8+ T-cell[CD45RA+CCR7+]:Change at Week 12Naïve CD8+ T-cell[CD45RA+CCR7+]:Change at Week 24Naïve CD8+ T-cell[CD45RA+CCR7+]:Change at Week 36Naïve CD8+ T-cell[CD45RA+CCR7+]:Change at Week 48Naïve CD8+ T-cell [CD45RA+]: BaselineNaïve CD8+ T-cell [CD45RA+]: Change at Week 4Naïve CD8+ T-cell [CD45RA+]: Change at Week 8Naïve CD8+ T-cell [CD45RA+]: Change at Week 12Naïve CD8+ T-cell [CD45RA+]: Change at Week 24Naïve CD8+ T-cell [CD45RA+]: Change at Week 36Naïve CD8+ T-cell [CD45RA+]: Change at Week 48Naïve Regulatory T-cells: BaselineNaïve Regulatory T-cells: Change at Week 4Naïve Regulatory T-cells: Change at Week 8Naïve Regulatory T-cells: Change at Week 12Naïve Regulatory T-cells: Change at Week 24Naïve Regulatory T-cells: Change at Week 36Naïve Regulatory T-cells: Change at Week 48Regulatory T-cells: BaselineRegulatory T-cells: Change at Week 4Regulatory T-cells: Change at Week 8Regulatory T-cells: Change at Week 12Regulatory T-cells: Change at Week 24Regulatory T-cells: Change at Week 36Regulatory T-cells: Change at Week 48Terminal Effector Regulatory T-cells: BaselineTerminal Effector Regulatory T-cells: CW 4Terminal Effector Regulatory T-cells: CW 8Terminal Effector Regulatory T-cells: CW 12Terminal Effector Regulatory T-cells: CW 24Terminal Effector Regulatory T-cells: CW 36Terminal Effector Regulatory T-cells: CW 48Th1 phenotype: BaselineTh1 phenotype: Change at Week 4Th1 phenotype: Change at Week 8Th1 phenotype: Change at Week 12Th1 phenotype: Change at Week 24Th1 phenotype: Change at Week 36Th1 phenotype: Change at Week 48Th17 phenotype: BaselineTh17 phenotype: Change at Week 4Th17 phenotype: Change at Week 8Th17 phenotype: Change at Week 12Th17 phenotype: Change at Week 24Th17 phenotype: Change at Week 36Th17 phenotype: Change at Week 48Th2-enriched phenotype: BaselineTh2-enriched phenotype: Change at Week 4Th2-enriched phenotype: Change at Week 8Th2-enriched phenotype: Change at Week 12Th2-enriched phenotype: Change at Week 24Th2-enriched phenotype: Change at Week 36Th2-enriched phenotype: Change at Week 48
Dimethyl Fumarate (BG00012)632.615.2-26.5-53.4-100.4-106.8-125.922.93.9-2.2-3.4-5.8-7.9-7.7275.418.2-21.7-50.8-91.8-99.3-114.310.40.6-1.2-2.1-3.5-3.8-4.01.10.0-0.20.0-0.4-0.4-0.34.81.20.40.50.60.30.217.32.5-0.3-1.6-3.2-4.1-4.264.61.4-5.1-11.7-26.0-33.6-30.181.22.5-5.5-18.2-38.1-48.3-49.3433.4-21.0-68.0-105.3-204.2-235.7-231.159.9-9.6-16.9-22.0-39.2-44.3-45.912.00.8-0.1-1.0-1.6-1.9-4.7101.41.7-15.9-15.2-42.8-55.6-50.9179.710.9-33.2-55.2-81.7-98.1-118.5129.07.6-22.8-41.0-69.9-80.3-90.356.10.6-7.1-12.7-20.3-25.8-25.1617.7-6.2-100.9-157.7-287.7-335.0-349.9187.5-4.7-40.9-64.0-108.6-124.9-136.3400.9-10.5-16.4-11.8-31.7-29.3-34.4416.7-8.6-15.6-10.2-33.6-30.2-37.0160.1-11.6-12.4-22.0-41.3-49.0-50.9258.0-11.7-28.3-39.7-82.4-106.1-103.415.8-0.1-0.4-0.7-0.40.1-0.171.51.0-7.3-13.3-20.0-25.7-24.4327.216.6-4.4-17.6-58.3-97.2-98.6329.5-14.7-65.4-102.1-159.2-183.0-187.461.9-0.5-7.3-1.1-24.6-35.1-30.1562.7-0.6-31.5-54.0-96.7-97.7-125.2

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: T-Cell Cytokines

T-cell cytokine subsets include IFN (interferon) g+ (% of CD4+ T cells), IFNg+ (% of CD8+ T cells), IFNg+ (% of memory CD4+ T cells), IFNg+ (% of memory CD8+ T cells), IL- (interleukin) 17A+/IFNg- (% of CD4+ T cells), IL-17A+/IFNg- (% of CD8+ T cells), IL-17A+/IFNg- (% of memory CD4+ T cells), IL-17A+/IFNg- (% of memory CD8+ T cells), IL-2+ (% of CD4+ T cells), IL-2+ (% of CD8+ T cells), IL-2+ (% of memory CD4+ T cells), IL-2+ (% of memory CD8+ T cells), IL-4+ (% of CD4+ T cells), IL-4+ (% of CD8+ T cells), IL-4+ (% of memory CD4+ T cells) and IL-4+ (% of memory CD8+ T cells). Here, Change at week is represented as CW. (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells/mm^3 (Mean)
IFNg+ (% of CD4+ T cells): BaselineIFNg+ (% of CD4+ T cells): Change at Week 4IFNg+ (% of CD4+ T cells): Change at Week 8IFNg+ (% of CD4+ T cells): Change at Week12IFNg+ (% of CD4+ T cells): Change at Week24IFNg+ (% of CD4+ T cells): Change at Week36IFNg+ (% of CD4+ T cells): Change at Week48IFNg+ (% of CD8+ T cells): BaselineIFNg+ (% of CD8+ T cells): Change at Week 4IFNg+ (% of CD8+ T cells): Change at Week 8IFNg+ (% of CD8+ T cells): Change at Week12IFNg+ (% of CD8+ T cells): Change at Week24IFNg+ (% of CD8+ T cells): Change at Week36IFNg+ (% of CD8+ T cells): Change at Week48IFNg+ (% of memory CD4+ T cells): BaselineIFNg+ (% of memory CD4+ T cells): CW 4IFNg+ (% of memory CD4+ T cells): CW 8IFNg+ (% of memory CD4+ T cells): CW 12IFNg+ (% of memory CD4+ T cells): CW 24IFNg+ (% of memory CD4+ T cells): CW 36IFNg+ (% of memory CD4+ T cells): CW 48IFNg+ (% of memory CD8+ T cells): BaselineIFNg+ (% of memory CD8+ T cells): CW 4IFNg+ (% of memory CD8+ T cells): CW 8IFNg+ (% of memory CD8+ T cells): CW 12IFNg+ (% of memory CD8+ T cells): CW 24IFNg+ (% of memory CD8+ T cells): CW 36IFNg+ (% of memory CD8+ T cells): CW 48IL-17A+/IFNg- (% of CD4+ T cells): BaselineIL-17A+/IFNg- (% of CD4+ T cells):Change at Week4IL-17A+/IFNg- (% of CD4+ T cells):Change at Week8IL-17A+/IFNg- (% of CD4+ T cells):Change at Week12IL-17A+/IFNg- (% of CD4+ T cells):Change at Week24IL-17A+/IFNg- (% of CD4+ T cells):Change at Week36IL-17A+/IFNg- (% of CD4+ T cells):Change at Week48IL-17A+/IFNg- (% of CD8+ T cells): BaselineIL-17A+/IFNg- (% of CD8+ T cells):Change at Week4IL-17A+/IFNg- (% of CD8+ T cells):Change at Week8IL-17A+/IFNg- (% of CD8+ T cells):Change at Week12IL-17A+/IFNg- (% of CD8+ T cells):Change at Week24IL-17A+/IFNg- (% of CD8+ T cells):Change at Week36IL-17A+/IFNg- (% of CD8+ T cells):Change at Week48IL-17A+/IFNg- (% of memory CD4+ T cells): BaselineIL-17A+/IFNg- (% of memory CD4+T cells): CW 4IL-17A+/IFNg- (% of memory CD4+T cells): CW 8IL-17A+/IFNg- (% of memory CD4+T cells): CW 12IL-17A+/IFNg- (% of memory CD4+T cells): CW 24IL-17A+/IFNg- (% of memory CD4+T cells): CW 36IL-17A+/IFNg- (% of memory CD4+T cells): CW 48IL-17A+/IFNg- (% of memory CD8+ T cells): BaselineIL-17A+/IFNg- (% of memory CD8+T cells): CW 4IL-17A+/IFNg- (% of memory CD8+T cells): CW 8IL-17A+/IFNg- (% of memory CD8+T cells): CW 12IL-17A+/IFNg- (% of memory CD8+T cells): CW 24IL-17A+/IFNg- (% of memory CD8+T cells): CW 36IL-17A+/IFNg- (% of memory CD8+T cells): CW 48IL-2+ (% of CD4+ T cells): BaselineIL-2+ (% of CD4+ T cells): Change at Week 4IL-2+ (% of CD4+ T cells): Change at Week 8IL-2+ (% of CD4+ T cells): Change at Week 12IL-2+ (% of CD4+ T cells): Change at Week 24IL-2+ (% of CD4+ T cells): Change at Week 36IL-2+ (% of CD4+ T cells): Change at Week 48IL-2+ (% of CD8+ T cells): BaselineIL-2+ (% of CD8+ T cells): Change at Week 4IL-2+ (% of CD8+ T cells): Change at Week 8IL-2+ (% of CD8+ T cells): Change at Week 12IL-2+ (% of CD8+ T cells): Change at Week 24IL-2+ (% of CD8+ T cells): Change at Week 36IL-2+ (% of CD8+ T cells): Change at Week 48IL-2+ (% of memory CD4+ T cells): BaselineIL-2+ (% of memory CD4+ T cells): Change at Week 4IL-2+ (% of memory CD4+ T cells): Change at Week 8IL-2+ (% of memory CD4+ T cells): Change at Week12IL-2+ (% of memory CD4+ T cells): Change at Week24IL-2+ (% of memory CD4+ T cells): Change at Week36IL-2+ (% of memory CD4+ T cells): Change at Week48IL-2+ (% of memory CD8+ T cells): BaselineIL-2+ (% of memory CD8+ T cells): Change at Week 4IL-2+ (% of memory CD8+ T cells): Change at Week 8IL-2+ (% of memory CD8+ T cells): Change at Week12IL-2+ (% of memory CD8+ T cells): Change at Week24IL-2+ (% of memory CD8+ T cells): Change at Week36IL-2+ (% of memory CD8+ T cells): Change at Week48IL-4+ (% of CD4+ T cells: BaselineIL-4+ (% of CD4+ T cells): Change at Week 4IL-4+ (% of CD4+ T cells): Change at Week 8IL-4+ (% of CD4+ T cells): Change at Week12IL-4+ (% of CD4+ T cells): Change at Week24IL-4+ (% of CD4+ T cells): Change at Week36IL-4+ (% of CD4+ T cells): Change at Week48IL-4+ (% of CD8+ T cells): BaselineIL-4+ (% of CD8+ T cells): Change at Week 4IL-4+ (% of CD8+ T cells): Change at Week 8IL-4+ (% of CD8+ T cells): Change at Week12IL-4+ (% of CD8+ T cells): Change at Week24IL-4+ (% of CD8+ T cells): Change at Week36IL-4+ (% of CD8+ T cells): Change at Week48IL-4+ (% of memory CD4+ T cells): BaselineIL-4+ (% of memory CD4+ T cells): Change at Week 4IL-4+ (% of memory CD4+ T cells): Change at Week 8IL-4+ (% of memory CD4+ T cells): Change at Week12IL-4+ (% of memory CD4+ T cells): Change at Week24IL-4+ (% of memory CD4+ T cells): Change at Week36IL-4+ (% of memory CD4+ T cells): Change at Week48IL-4+ (% of memory CD8+ T cells): BaselineIL-4+ (% of memory CD8+ T cells): Change at Week 4IL-4+ (% of memory CD8+ T cells): Change at Week 8IL-4+ (% of memory CD8+ T cells): Change at Week12IL-4+ (% of memory CD8+ T cells): Change at Week24IL-4+ (% of memory CD8+ T cells): Change at Week36IL-4+ (% of memory CD8+ T cells): Change at Week48
Dimethyl Fumarate (BG00012)3.3400.090-0.356-0.729-1.134-1.511-1.2226.1660.493-0.264-1.345-1.650-1.922-1.3064.5180.050-0.295-0.851-1.019-1.804-1.3698.7950.360-0.285-1.543-0.964-2.035-0.4971.2440.1150.1310.4700.1650.4191.6930.4550.2390.0320.3010.2890.9111.4571.0750.0000.0400.3730.2280.3331.2550.1550.1130.0270.0640.2540.2700.6805.1770.0620.149-0.069-0.448-1.837-1.8401.180-0.081-0.227-0.2622-0.525-0.547-0.2487.053-0.1050.0560.0120.015-2.140-1.9461.879-0.218-0.318-0.115-0.461-0.803-0.3151.261-0.150-0.113-0.370-0.170-0.3760.2811.107-0.222-0.189-0.553-0.032-0.1950.7861.406-0.128-0.141-0.412-0.136-0.2660.3251.376-0.180-0.269-0.7950.416-0.2841.836

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Change From Baseline in Lymphocyte Subsets Counts up to 48 Weeks: B-Cell Subsets

B-cell subsets include CD10+ Transitional B cells, CD138+ Plasma Cells, Ig (Immunoglobulin) D+ Memory B cells [non-class switched], IgD- Memory B cells [class switched], Naïve B cells, Plasma Cells [CD10-], Transitional B-cells and Plasmablasts. Here, Change at week is represented as CW. (NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventioncells/mm^3 (Mean)
CD10+ Transitional B cells: BaselineCD10+ Transitional B cells: Change at Week 4CD10+ Transitional B cells: Change at Week 8CD10+ Transitional B cells: Change at Week 12CD10+ Transitional B cells: Change at Week 24CD10+ Transitional B cells: Change at Week 36CD10+ Transitional B cells: Change at Week 48CD138+ Plasma Cells: BaselineCD138+ Plasma Cells: Change at Week 4CD138+ Plasma Cells: Change at Week 8CD138+ Plasma Cells: Change at Week 12CD138+ Plasma Cells: Change at Week 24CD138+ Plasma Cells: Change at Week 36CD138+ Plasma Cells: Change at Week 48IgD+ Memory B cells [non-class switched]: BaselineIgD+ Memory B cells[non-class switched]: CW 4IgD+ Memory B cells[non-class switched]: CW 8IgD+ Memory B cells[non-class switched]: CW 12IgD+ Memory B cells[non-class switched]: CW 24IgD+ Memory B cells[non-class switched]: CW 36IgD+ Memory B cells [non-class switched]: CW 48IgD- Memory B cells [class switched]: BaselineIgD- Memory B cells [class switched]: CW 4IgD- Memory B cells [class switched]: CW 8IgD- Memory B cells [class switched]: CW 12IgD- Memory B cells [class switched]: CW 24IgD- Memory B cells [class switched]: CW 36IgD- Memory B cells [class switched]: CW 48Naïve B cells: BaselineNaïve B cells: Change at Week 4Naïve B cells: Change at Week 8Naïve B cells: Change at Week 12Naïve B cells: Change at Week 24Naïve B cells: Change at Week 36Naïve B cells: Change at Week 48Plasma Cells [CD10-]: BaselinePlasma Cells [CD10-]: Change at Week 4Plasma Cells [CD10-]: Change at Week 8Plasma Cells [CD10-]: Change at Week 12Plasma Cells [CD10-]: Change at Week 24Plasma Cells [CD10-]: Change at Week 36Plasma Cells [CD10-]: Change at Week 48Transitional B-cells: BaselineTransitional B-cells: Change at Week 4Transitional B-cells: Change at Week 8Transitional B-cells: Change at Week 12Transitional B-cells: Change at Week 24Transitional B-cells: Change at Week 36Transitional B-cells: Change at Week 48Plasmablasts: BaselinePlasmablasts: Change at Week 4Plasmablasts: Change at Week 8Plasmablasts: Change at Week 12Plasmablasts: Change at Week 24Plasmablasts: Change at Week 36Plasmablasts: Change at Week 48
Dimethyl Fumarate (BG00012)9.4-1.2-0.4-0.43.62.85.70.26-0.02-0.12-0.15-0.21-0.21-0.1937.8-8.9-12.4-12.1-17.6-19.6-13.450.4-8.7-17.7-23.1-29.549.95-27.4197.2-21.5-37.2-43.1-45.7-54.0-35.60.63-0.02-0.11-0.18-0.34-0.33-0.3813.6-1.30.60.75.84.27.30.91-0.04-0.21-0.31-0.46-0.46-0.50

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Change From Baseline in Immunoglobulin M (IgM) up to 48 Weeks

(NCT02525874)
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48

Interventionmg/L (Mean)
BaselineChange at Week 4Change at Week 8Change at Week 12Change at Week 24Change at Week 36Change at Week 48
Dimethyl Fumarate (BG00012)1330.1-68.9-23.2-18.8-36.9-19.4-96.8

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Number of Participants Experiencing Disability Progression

Measured by at least a 1.0-point increase on the EDSS from baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from baseline EDSS = 0 that is sustained for 24 weeks. (NCT02555215)
Timeframe: Baseline to Week 96

InterventionParticipants (Count of Participants)
Dimethyl Fumarate3

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Percentage of Participants Experiencing One or More Relapses

Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Investigator. New or recurrent neurologic symptoms that evolved gradually over months were considered disability progression, not an acute relapse, and were not treated with steroids. (NCT02555215)
Timeframe: Baseline to Week 96

Interventionpercentage of participants (Number)
Dimethyl Fumarate10

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Change From Baseline in the Degree of Disability

The Expanded Disability Status Scale (EDSS) measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. (NCT02555215)
Timeframe: Baseline to Week 96

Interventionscore on a scale (Mean)
BaselineChange from Baseline at Week 12Change from Baseline at Week 24Change from Baseline at Week 36Change from Baseline at Week 48Change from Baseline at Week 72Change from Baseline at Week 96
Dimethyl Fumarate1.000.150.290.270.500.710.21

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Total Number of New or Newly Enlarging T2 Hyperintense Lesions From Week 16 to Week 24

T2 hyperintense lesions were measured by MRI brain scans. (NCT02555215)
Timeframe: Week 16 to Week 24

InterventionParticipants (Count of Participants)
0 lesions1 lesion2 lesions3 lesions4 lesions5 or more lesions
Dimethyl Fumarate1221101

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Total Number of New or Newly Enlarging T2 Hyperintense Lesions From Week 64 to Week 72

T2 hyperintense lesions were measured by MRI brain scans. (NCT02555215)
Timeframe: Week 64 to Week 72

InterventionParticipants (Count of Participants)
0 lesions1 lesion2 lesions3 lesions4 lesions5 or more lesions
Dimethyl Fumarate811000

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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence that does not necessarily have a causal relationship with treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. (NCT02555215)
Timeframe: Baseline to Week 96

Interventionparticipants (Number)
AESAE
Dimethyl Fumarate182

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Average Annualized Relapse Rate (ARR)

"Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Investigator. New or recurrent neurologic symptoms that evolved gradually over months were considered disability progression, not an acute relapse, and were not treated with steroids.~The ARR was calculated as the total number of relapses that occurred during the previous 12 months and during the 120 weeks on treatment for participants in Study 109MS202 that continued into Study 109MS311, divided by the total number of person-years followed prior to the study and by the total number of person-years followed during the study, respectively." (NCT02555215)
Timeframe: Baseline to Week 96

Interventionrelapses per person-years (Number)
Dimethyl Fumarate0.1

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Number of Participants Discontinuing Treatment Due to an Adverse Event

An AE is any untoward medical occurrence that does not necessarily have a causal relationship with treatment. (NCT02555215)
Timeframe: Baseline to Week 96

Interventionparticipants (Number)
Dimethyl Fumarate0

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The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)

The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination from randomization into the trial. (NCT02739542)
Timeframe: 96 weeks

Interventionweeks (Mean)
Tecfidera89.69
Placebo77.81

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Number of Newly Enlarging T2 Lesions

Number of newly enlarging T2 lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group. (NCT02739542)
Timeframe: 96 weeks

InterventionT2 lesions (Mean)
Tecfidera0.03
Placebo0.10

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Number of New T2 Lesions

Number of new T2 lesions as measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group. (NCT02739542)
Timeframe: 96 weeks

InterventionT2 lesions (Mean)
Tecfidera0.09
Placebo0.54

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Number of Contrast Enhancing Lesions

Number of contrast enhancing lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group. (NCT02739542)
Timeframe: 96 weeks

Interventioncontrast enhancing lesions (Mean)
Tecfidera0.07
Placebo0

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Newly Enlarging T2 Lesions and New T2 Lesions Combined

Newly enlarging T2 lesions and new T2 lesions combined is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group. (NCT02739542)
Timeframe: 96 weeks

InterventionT2 lesions (Mean)
Tecfidera0.12
Placebo0.62

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Change in Lesion Volume on T2-weighted MRI

Change in lesion volume on T2-weighted MRI is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group. (NCT02739542)
Timeframe: Baseline, 96 weeks

Interventionmm³ (Mean)
Tecfidera0.005
Placebo0.04

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Incidence of Dose Limiting Toxicity

The incidence of dose limiting toxicities (DLTs) will be used to define the maximum tolerated dose or biologically active dose for potential phase 2 studies. (NCT02784834)
Timeframe: 2 months

InterventionParticipants (Count of Participants)
Dimethyl Fumarate (DMF)0

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Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24

Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Baseline, Week 24

Interventioncc (Mean)
Placebo-0.023
Evobrutinib 25 mg QD0.057
Evobrutinib 75 mg QD-0.111
Evobrutinib 75 mg BID-0.051
Tecfidera-0.050

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Annualized Relapse Rate (ARR)

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. (NCT02975349)
Timeframe: Week 0 to Week 48

Interventionrelapses per year (Mean)
Placebo Then Evobrutinib 25 mg QD0.37
Evobrutinib 25 mg QD0.52
Evobrutinib 75 mg QD0.25
Evobrutinib 75 mg BID0.11
Tecfidera0.14

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Annualized Relapse Rate (ARR) at Week 24

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 24

Interventionrelapses per year (Mean)
Placebo0.37
Evobrutinib 25 mg QD0.57
Evobrutinib 75 mg QD0.13
Evobrutinib 75 mg BID0.08
Tecfidera0.20

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Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24

Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans. (NCT02975349)
Timeframe: Week 24 to Week 48

InterventionLesions (Mean)
Placebo Then Evobrutinib 25 mg QD3.57
Evobrutinib 25 mg QD5.86
Evobrutinib 75 mg QD3.84
Evobrutinib 75 mg BID1.60
Tecfidera1.88

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Total Number of New or Enlarging T2 Lesions

Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 12 to Week 24

InterventionLesions (Mean)
Placebo5.96
Evobrutinib 25 mg QD6.52
Evobrutinib 75 mg QD3.41
Evobrutinib 75 mg BID2.19
Tecfidera5.35

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Total Number of New Gadolinium-positive (Gd+) T1 Lesions

Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 12 to 24

InterventionLesions (Mean)
Placebo3.08
Evobrutinib 25 mg QD3.44
Evobrutinib 75 mg QD1.20
Evobrutinib 75 mg BID0.98
Tecfidera3.24

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Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48

The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). (NCT02975349)
Timeframe: Week 24, Week 48

InterventionUnits on a scale (Mean)
Placebo Then Evobrutinib 25 mg QD-0.05
Evobrutinib 25 mg QD-0.10
Evobrutinib 75 mg QD-0.01
Evobrutinib 75 mg BID0.00
Tecfidera-0.10

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Qualified Relapse-Free Status at Week 24

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Placebo77.4
Evobrutinib 25 mg QD74.0
Evobrutinib 75 mg QD88.2
Evobrutinib 75 mg BID86.8
Tecfidera88.9

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Qualified Relapse-free Status

A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status were reported. (NCT02975349)
Timeframe: Week 25 to Week 48

Interventionpercentage of participants (Number)
Placebo Then Evobrutinib 25 mg QD84.1
Evobrutinib 25 mg QD86.4
Evobrutinib 75 mg QD78.3
Evobrutinib 75 mg BID91.1
Tecfidera96.0

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Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48

Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. (NCT02975349)
Timeframe: Week 48

InterventionLesions (Mean)
Placebo Then Evobrutinib 25 mg QD0.95
Evobrutinib 25 mg QD1.84
Evobrutinib 75 mg QD0.85
Evobrutinib 75 mg BID0.49
Tecfidera0.42

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Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs. (NCT02975349)
Timeframe: Baseline up to Safety Follow-up (Week 52)

,,,,,
InterventionParticipants (Count of Participants)
TEAEsSerious TEAEsTEAEs Leading to Death
Evobrutinib 25 mg QD2820
Evobrutinib 75 mg BID3440
Evobrutinib 75 mg QD3520
Placebo2420
Placebo Then Evobrutinib 25 mg QD1900
Tecfidera3520

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Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values

Hematology, biochemistry, and urinalysis values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). For the hematology and biochemistry parameters, participants with a value grade 3 or higher were reported. For the urinalysis parameters, participants with a value grade 3 or higher, or a value >= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported. (NCT02975349)
Timeframe: Baseline up to Safety Follow-up (Week 52)

,,,,,
InterventionParticipants (Count of Participants)
Grade >= 3 hematology valuesGrade >= 3 biochemistry valuesGrade >= 3 or value >= 2 ULN or ++ Increasing urinalysis values
Evobrutinib 25 mg QD061
Evobrutinib 75 mg BID0162
Evobrutinib 75 mg QD192
Placebo020
Placebo Then Evobrutinib 25 mg QD282
Tecfidera196

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Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)

Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator. (NCT02975349)
Timeframe: Baseline up to Safety Follow-up (Week 52)

,,,,,
InterventionParticipants (Count of Participants)
Vital Sign AbnormalitiesECG Abnormalities
Evobrutinib 25 mg QD00
Evobrutinib 75 mg BID00
Evobrutinib 75 mg QD00
Placebo00
Placebo Then Evobrutinib 25 mg QD00
Tecfidera00

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Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)

Change in the serum levels of IgG, IgA, IgM were assessed. (NCT02975349)
Timeframe: Baseline (Day 1), Weeks 4, 16, and 24

,,,,
InterventionGram per Liter (Mean)
Ig A, Week 4Ig A, Week 16Ig A, Week 24Ig G, Week 4Ig G, Week 16Ig G, Week 24Ig M, Week 4Ig M, Week 16Ig M, Week 24
Evobrutinib 25 mg QD0.020.180.21-0.10-0.070.00-0.06-0.12-0.14
Evobrutinib 75 mg BID0.070.220.220.02-0.05-0.28-0.05-0.14-0.21
Evobrutinib 75 mg QD0.040.210.18-0.02-0.10-0.15-0.12-0.18-0.20
Placebo-0.020.100.060.020.040.06-0.010.020.04
Tecfidera-0.13-0.02-0.06-0.420.07-0.23-0.04-0.00-0.00

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Change From Baseline in Absolute B Cells (Active Treatment Period)

Change from baseline in absolute B cells are reported. (NCT02975349)
Timeframe: Baseline (Day 1), Weeks 4, and 24

,,,,
Interventioncells per micro-liter (Mean)
Week 4Week 24
Evobrutinib 25 mg QD913
Evobrutinib 75 mg BID50-9
Evobrutinib 75 mg QD31-15
Placebo-57
Tecfidera-3-26

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Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24

The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Baseline, Week 24

InterventionUnits on a scale (Mean)
Placebo-0.03
Evobrutinib 25 mg QD0.02
Evobrutinib 75 mg QD-0.14
Evobrutinib 75 mg BID0.04
Tecfidera0.02

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Absolute Numbers of B Cells (Active Treatment Period)

Absolute Numbers of B Cells are reported. (NCT02975349)
Timeframe: Baseline (Day 1), Weeks 4, and 24

,,,,
Interventioncells per micro-liter (Mean)
Day 1Week 4Week 24
Evobrutinib 25 mg QD208220230
Evobrutinib 75 mg BID219270214
Evobrutinib 75 mg QD247277235
Placebo242243264
Tecfidera210201180

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Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48

Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. (NCT02975349)
Timeframe: Week 48

InterventionLesions (Mean)
Placebo Then Evobrutinib 25 mg QD1.00
Evobrutinib 25 mg QD1.91
Evobrutinib 75 mg QD0.85
Evobrutinib 75 mg BID0.49
Tecfidera0.42

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Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions

Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 12 to Week 24

InterventionLesions (Mean)
Placebo1.02
Evobrutinib 25 mg QD1.31
Evobrutinib 75 mg QD0.42
Evobrutinib 75 mg BID0.34
Tecfidera1.45

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Change From Week 24 in Volume of T2 Lesions at Week 48

Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. (NCT02975349)
Timeframe: Week 24, Week 48

Interventioncc (Mean)
Placebo Then Evobrutinib 25 mg QD0.53
Evobrutinib 25 mg QD0.67
Evobrutinib 75 mg QD0.35
Evobrutinib 75 mg BID-0.03
Tecfidera-0.57

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Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48

Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. (NCT02975349)
Timeframe: Week 24, Week 48

Interventioncc (Mean)
Placebo Then Evobrutinib 25 mg QD0.092
Evobrutinib 25 mg QD0.088
Evobrutinib 75 mg QD0.045
Evobrutinib 75 mg BID0.024
Tecfidera-0.203

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Total Number of Gadolinium-Enhancing T1 Lesions

Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Week 12 to Week 24

InterventionLesions (Mean)
Placebo3.85
Evobrutinib 25 mg QD4.06
Evobrutinib 75 mg QD1.69
Evobrutinib 75 mg BID1.15
Tecfidera4.78

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Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)

Absolute Concentrations serum levels of IgG, IgA, IgM were assessed. (NCT02975349)
Timeframe: Baseline (Day 1), Weeks 4, 16, and 24

,,,,
InterventionGram per Liter (Mean)
Ig A, Day 1Ig A, Week 4Ig A, Week 16Ig A, Week 24Ig G, Day 1Ig G, Week 4Ig G, Week 16Ig G, Week 24Ig M, Day 1Ig M, Week 4Ig M, Week 16Ig M, Week 24
Evobrutinib 25 mg QD1.891.922.102.129.439.349.419.461.271.211.131.03
Evobrutinib 75 mg BID1.871.942.082.099.629.649.569.361.331.281.201.08
Evobrutinib 75 mg QD1.901.932.132.099.819.799.709.621.441.321.241.20
Placebo1.991.982.071.999.619.649.689.661.421.401.431.44
Tecfidera2.031.902.031.979.479.059.589.271.271.231.281.29

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Change From Baseline in Volume of T2 Lesions at Week 24

Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis. (NCT02975349)
Timeframe: Baseline, Week 24

Interventioncubic centimeter (cc) (Mean)
Placebo0.42
Evobrutinib 25 mg QD0.93
Evobrutinib 75 mg QD-0.01
Evobrutinib 75 mg BID0.09
Tecfidera0.47

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6 Minute Walk Distance (6MWD)

The primary outcome of clinical efficacy in this study is improvement in 6-minute walk distance (6MWD). Data depict the mean change (%) at end-of-study-treatment (Week 24) from baseline in both treatment groups, utilizing the Last Observation Carried Forward of withdrawn subjects. (NCT02981082)
Timeframe: Baseline to Week 24

Interventionpercent change (Mean)
Dimethyl Fumarate (DMF)-7.07
Placebo-14.97

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Number of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT03093324)
Timeframe: End of study (up to Week 10)

Interventionparticipants (Number)
ALKS 8700198
Dimethyl Fumarate (DMF)210

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Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87000.9
Dimethyl Fumarate (DMF)1.5

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Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for Part B

Interventiondays (Mean)
ALKS 87001.3
Dimethyl Fumarate (DMF)2.2

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Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87002.9
Dimethyl Fumarate (DMF)3.9

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Number of Days With a Global GI Symptom and Impact Scale (GGISIS) Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B

GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87002.1
Dimethyl Fumarate (DMF)2.8

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Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B

GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87000.7
Dimethyl Fumarate (DMF)0.9

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Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B

GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87001.1
Dimethyl Fumarate (DMF)1.5

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Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. Scores were averaged for 5-week treatment period. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

,
Interventionscore on a scale (Mean)
NauseaVomitingUpper Abdominal PainLower Abdominal PainDiarrhea
ALKS 87000.90.20.80.81.1
Dimethyl Fumarate (DMF)1.20.61.31.01.3

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Number of Days With Any Individual Gastrointestinal Symptom and Impact Scale (IGISIS) Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. (NCT03093324)
Timeframe: End of treatment (up to Week 6) for both Parts A and B

Interventiondays (Mean)
ALKS 87001.5
Dimethyl Fumarate (DMF)2.5

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HADS Total Score-Depression: Change From Baseline to Week 24

The HADS was a patient-reported questionnaire used to assess the level of anxiety and depression in the setting of a hospital medical outpatient clinic. The anxiety and depression subscales each have a range from 0-21, higher scores indicated higher levels of anxiety and depression, respectively. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-1.7
Risankizumab-4.8

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Hospital Anxiety & Depression Scale (HADS) Total Score-Anxiety: Change From Baseline to Week 16

The HADS was a patient-reported questionnaire used to assess the level of anxiety and depression in the setting of a hospital medical outpatient clinic. The anxiety and depression subscales each have a range from 0-21, higher scores indicated higher levels of anxiety and depression, respectively. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-2.2
Risankizumab-4.3

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Nail Psoriasis Severity Index (NAPSI): Change From Baseline to Week 16

The NAPSI score is calculated by summing the scores of all the nails which for each nail are the sum of the nail matrix score and nail bed score. Each of these is scored as 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. Each nail has a matrix score (0-4) and a nail bed score (0-4). The total nail score is the sum of those 2 (nail matrix and nail bed) individual scores (0-8). The sum of the total score of all involved fingernails is then the total NAPSI score. The NAPSI score is calculated only if all questions in the case report form are completed. A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-2.2
Risankizumab-13.6

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NAPPA-CLIN Total Score: Change From Baseline to Week 24

The NAPPA-CLIN is an investigator assessment used to assess the severity of nail matrix psoriasis (leukonychia, red spots, dots, nail plate crumbling) and psoriasis of the nail bed (oil drop, splinter haemorrhage, subungual hyperkeratosis, onycholysis). NAPPA-CLIN has been developed from the NAPSI score, a nail psoriasis-specific score, which in its original version comprises the assessment of matrix and nail bed involvement in every finger and toe by 2 criteria for each nail. The NAPPA-CLIN is a simplified version of the NAPSI which only assesses the least and the worst involved nail of both hands or both feet respectively. Thus, the NAPPA-CLIN scores for hands or feet range from 0 to 16. A higher score indicates a worse involvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-0.7
Risankizumab-3.7

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NAPSI: Change From Baseline to Week 24

The NAPSI score is calculated by summing the scores of all the nails which for each nail are the sum of the nail matrix score and nail bed score. Each of these is scored as 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. Each nail has a matrix score (0-4) and a nail bed score (0-4). The total nail score is the sum of those 2 (nail matrix and nail bed) individual scores (0-8). The sum of the total score of all involved fingernails is then the total NAPSI score. The NAPSI score is calculated only if all questions in the case report form are completed. A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-4.4
Risankizumab-18.1

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Participants With Baseline NAPSI ˃0: Change From Baseline to Week 16

The NAPSI score is calculated by summing the scores of all the nails which for each nail are the sum of the nail matrix score and nail bed score. Each of these is scored as 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. Each nail has a matrix score (0-4) and a nail bed score (0-4). The total nail score is the sum of those 2 (nail matrix and nail bed) individual scores (0-8). The sum of the total score of all involved fingernails is then the total NAPSI score. The NAPSI score is calculated only if all questions in the case report form are completed. A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-4.2
Risankizumab-21.4

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Participants With Baseline NAPSI ˃0: Change From Baseline to Week 24

The NAPSI score is calculated by summing the scores of all the nails which for each nail are the sum of the nail matrix score and nail bed score. Each of these is scored as 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. Each nail has a matrix score (0-4) and a nail bed score (0-4). The total nail score is the sum of those 2 (nail matrix and nail bed) individual scores (0-8). The sum of the total score of all involved fingernails is then the total NAPSI score. The NAPSI score is calculated only if all questions in the case report form are completed. A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-6.0
Risankizumab-27.5

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PASI: Change From Baseline to Week 12

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 12

Interventionunits on a scale (Least Squares Mean)
Fumaderm-7.69
Risankizumab-16.49

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Palmoplantar Psoriasis Severity Index (PPASI): Change From Baseline to Week 16

The PPASI is an assessment by the investigator that provides a numeric scoring for psoriasis affecting the hands and feet with scores ranging from 0 to 72. It is a linear combination of percent of surface area of palms and soles that are affected and the severity of erythema, induration, and desquamation. The higher the score, the greater the severity of psoriasis symptoms. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-0.76
Risankizumab-1.04

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Body Surface Area (BSA) Affected by Psoriasis: Change From Baseline to Week 4

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 4

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-0.3
Risankizumab-5.2

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BSA Affected by Psoriasis: Change From Baseline to Week 12

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 12

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-6.0
Risankizumab-16.2

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BSA Affected by Psoriasis: Change From Baseline to Week 16

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-8.2
Risankizumab-18.0

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BSA Affected by Psoriasis: Change From Baseline to Week 20

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 20

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-9.7
Risankizumab-19.3

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BSA Affected by Psoriasis: Change From Baseline to Week 24

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-9.8
Risankizumab-19.8

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BSA Affected by Psoriasis: Change From Baseline to Week 8

BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 8

Interventionpercentage estimated body surface area (Least Squares Mean)
Fumaderm-3.5
Risankizumab-12.8

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Clinical Severity of Nail Psoriasis (NAPPA-CLIN) Total Score: Change From Baseline to Week 16

The NAPPA-CLIN is an investigator assessment used to assess the severity of nail matrix psoriasis (leukonychia, red spots, dots, nail plate crumbling) and psoriasis of the nail bed (oil drop, splinter haemorrhage, subungual hyperkeratosis, onycholysis). NAPPA-CLIN has been developed from the Nail Psoriasis Severity Index (NAPSI) score, a nail psoriasis-specific score, which in its original version comprises the assessment of matrix and nail bed involvement in every finger and toe by 2 criteria for each nail. The NAPPA-CLIN is a simplified version of the NAPSI which only assesses the least and the worst involved nail of both hands or both feet respectively. Thus, the NAPPA-CLIN scores for hands or feet range from 0 to 16. A higher score indicates a worse involvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-0.4
Risankizumab-2.7

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DLQI Total Score: Change From Baseline to Week 16

The DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 1 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-9.7
Risankizumab-17.0

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DLQI: Change From Baseline to Week 24

The DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 1 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-11.2
Risankizumab-18.8

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EQ-5D-5L Total Score: Change From Baseline to Week 24

The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. The EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the subject's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm0.106
Risankizumab0.165

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EQ-5D-5L VAS: Change From Baseline to Week 24

The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale numbered from 100 (best health imagined) to 0 (worst health imagined). The VAS score from the scale is then entered as a number by the participant. This can be used as a quantitative measure of health outcome that reflects the participant's own judgement. An increase in the EQ-5D-5L VAS score indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm11.6
Risankizumab28.4

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EQ-5D-5L Visual Analog Scale (VAS): Change From Baseline to Week 16

The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale numbered from 100 (best health imagined) to 0 (worst health imagined). The VAS score from the scale is then entered as a number by the participant. This can be used as a quantitative measure of health outcome that reflects the participant's own judgement. An increase in the EQ-5D-5L VAS score indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm11.0
Risankizumab26.0

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European Quality of Life 5 Dimensions (EQ-5D-5L) Total Score: Change From Baseline to Week 16

The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. The EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the subject's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm0.083
Risankizumab0.171

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Summary of PBI at Week 24

"The PBI is a patient-reported outcome instrument that assesses the benefit of psoriasis treatment. The PBI is a patient-reported outcome instrument that assesses the benefit of psoriasis treatment.The PBI assessment consists of 2 steps: before treatment, every participant defines his/her treatment needs according to a standardized list (PNQ). After treatment, the participant rates the degree of benefits achieved (PBQ). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for did not apply to me (5) and missing. For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score. An increase in PBI indicates improvement. LOCF imputation was used for missing data." (NCT03255382)
Timeframe: Baseline Week 24

Interventionunits on a scale (Mean)
Fumaderm1.997
Risankizumab3.316

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Summary of Patient Benefit Index (PBI) at Week 16

"The PBI is a patient-reported outcome instrument that assesses the benefit of psoriasis treatment.The PBI assessment consists of 2 steps: before treatment, every participant defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire [PNQ]). After treatment, the participant rates the degree of benefits achieved (Patient Benefits Questionnaire [PBQ]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for did not apply to me (5) and missing. For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score. An increase in PBI indicates improvement. LOCF imputation was used for missing data." (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Mean)
Fumaderm1.970
Risankizumab3.118

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Short Form Health Survey 36, Version 2 (SF-36 V2) Physical Component Summary (PCS) Score: Change From Baseline to Week 16

The SF-36 V2 Health determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (PCS Score; range = 0-100); a positive change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm2.87
Risankizumab7.36

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SF-36 V2 PCS Score: Change From Baseline to Week 24

The SF-36 V2 Health determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (PCS Score; range = 0-100); a positive change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm3.68
Risankizumab8.31

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SF-36 V2 Mental Component Summary (MCS) Score: Change From Baseline: to Week 16

The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (MCS Score; range = 0-100); a positive change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm4.20
Risankizumab10.86

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SF-36 V2 MCS Score: Change From Baseline to Week 24

The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (MCS Score; range = 0-100); a positive change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm3.56
Risankizumab11.41

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PtGA: Change From Baseline to Week 24

"The PtGA is a patient-reported outcome instrument to assess the patient's assessment of disease severity. This self-reported measure is used to assess disease activity using a 4-point scale where a higher score indicates a higher level of disease activity. Disease activity is assessed from 0 (complete disease control) to 3 (uncontrolled disease). LOCF imputation was used for missing data." (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-1.0
Risankizumab-2.0

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PSSI: Change From Baseline at Week 24

The physician assessed the severity of scalp psoriasis using the PSSI, which consists of an assessment of erythema, induration, and desquamation on a scale from 0 (none) to 4 (very severe) and the percentage of scalp involved on a scale from 0 (0% of scalp involved) to 6 (90-100% of scalp involved). The composite score is calculated as the sum of symptom scores multiplied by the score for the area of scalp involved. The PSSI ranges from 0 (best) to 72 (worst). A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-13.9
Risankizumab-22.0

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PSS Total Score: Change From Baseline to Week 24

The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-5.6
Risankizumab-9.5

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PSS Total Score: Change From Baseline to Week 16

The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-5.5
Risankizumab-8.7

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Psoriasis Scalp Severity Index (PSSI): Change From Baseline at Week 16

The physician assessed the severity of scalp psoriasis using the PSSI, which consists of an assessment of erythema, induration, and desquamation on a scale from 0 (none) to 4 (very severe) and the percentage of scalp involved on a scale from 0 (0% of scalp involved) to 6 (90-100% of scalp involved). The composite score is calculated as the sum of symptom scores multiplied by the score for the area of scalp involved. The PSSI ranges from 0 (best) to 72 (worst). A negative change from Baseline indicates improvement. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-14.6
Risankizumab-21.2

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Psoriasis Area and Severity Index (PASI): Change From Baseline to Week 4

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Last observation carried forward (LOCF) imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 4

Interventionunits on a scale (Least Squares Mean)
Fumaderm-2.37
Risankizumab-9.56

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PPASI: Change From Baseline to Week 24

The PPASI is an assessment by the investigator that provides a numeric scoring for psoriasis affecting the hands and feet with scores ranging from 0 to 72. It is a linear combination of percent of surface area of palms and soles that are affected and the severity of erythema, induration, and desquamation. The higher the score, the greater the severity of psoriasis symptoms. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-0.87
Risankizumab-1.17

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Percentage of Participants With PSS Score of 0 at Week 24

The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm3.3
Risankizumab41.7

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Percentage of Participants With Psoriasis Symptoms Scale (PSS) Score of 0 at Week 16

The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm5.0
Risankizumab25.0

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Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 4

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm3.3
Risankizumab33.3

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Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 8

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm15.0
Risankizumab81.7

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Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 24

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm38.3
Risankizumab93.3

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Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 20

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm48.3
Risankizumab93.3

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HADS Total Score-Anxiety: Change From Baseline to Week 24

The HADS was a patient-reported questionnaire used to assess the level of anxiety and depression in the setting of a hospital medical outpatient clinic. The anxiety and depression subscales each have a range from 0-21, higher scores indicated higher levels of anxiety and depression, respectively. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-1.8
Risankizumab-4.0

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Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm33.3
Risankizumab90.0

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Percentage of Participants Achieving sPGA Score of Clear at Week 8

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm1.7
Risankizumab10.0

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Percentage of Participants Achieving sPGA Score of Clear at Week 4

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm0
Risankizumab1.7

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 16

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm60.0
Risankizumab100

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Percentage of Participants Achieving sPGA Score of Clear at Week 24

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm5.0
Risankizumab51.7

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Percentage of Participants Achieving sPGA Score of Clear at Week 20

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm6.7
Risankizumab48.3

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Percentage of Participants Achieving sPGA Score of Clear at Week 16

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm3.3
Risankizumab36.7

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Percentage of Participants Achieving sPGA Score of Clear at Week 12

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm3.3
Risankizumab21.7

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Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 24

The DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 1 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm10.0
Risankizumab66.7

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Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16

The DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 1 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm10.0
Risankizumab48.3

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Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI90) at Week 24

The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. Non-responder imputation (NRI) was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm10.0
Risankizumab83.3

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Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 8

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm1.7
Risankizumab38.3

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Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 4

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm0
Risankizumab1.7

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Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 20

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm16.7
Risankizumab83.3

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Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 16

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm11.7
Risankizumab76.7

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Percentage of Participants Achieving 90% Improvement in PASI Score (PASI90) at Week 12

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm5.0
Risankizumab61.7

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 8

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm8.3
Risankizumab75.0

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 4

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm3.3
Risankizumab13.3

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 24

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm33.3
Risankizumab98.3

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Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm31.7
Risankizumab91.7

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 16

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm26.7
Risankizumab93.3

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 12

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm20.0
Risankizumab86.7

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 8

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm28.3
Risankizumab91.7

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 4

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm6.7
Risankizumab53.3

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 24

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm53.3
Risankizumab100

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 20

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm63.3
Risankizumab100

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Percentage of Participants Achieving 50% Improvement in PASI Score (PASI50) at Week 12

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI50 is defined as at least a 50% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm46.7
Risankizumab100

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 8

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Fumaderm1.7
Risankizumab5.0

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 4

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 4

Interventionpercentage of participants (Number)
Fumaderm0
Risankizumab0

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 24

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Fumaderm5.0
Risankizumab50.0

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 20

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm6.7
Risankizumab48.3

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 16

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Fumaderm1.7
Risankizumab35.0

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Percentage of Participants Achieving 100% Improvement in PASI (PASI100) at Week 12

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 12

Interventionpercentage of participants (Number)
Fumaderm1.7
Risankizumab23.3

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Patient's Global Assessment (PtGA): Change From Baseline to Week 16

"The PtGA is a patient-reported outcome instrument to assess the patient's assessment of disease severity. This self-reported measure is used to assess disease activity using a 4-point scale where a higher score indicates a higher level of disease activity. Disease activity is assessed from 0 (complete disease control) to 3 (uncontrolled disease). LOCF imputation was used for missing data." (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-1.0
Risankizumab-1.9

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PASI: Change From Baseline to Week 8

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 8

Interventionunits on a scale (Least Squares Mean)
Fumaderm-5.61
Risankizumab-15.18

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PASI: Change From Baseline to Week 24

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 24

Interventionunits on a scale (Least Squares Mean)
Fumaderm-9.31
Risankizumab-17.69

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PASI: Change From Baseline to Week 20

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 20

Interventionunits on a scale (Least Squares Mean)
Fumaderm-9.46
Risankizumab-17.35

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PASI: Change From Baseline to Week 16

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-9.11
Risankizumab-16.89

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HADS Total Score-Depression: Change From Baseline to Week 16

The HADS was a patient-reported questionnaire used to assess the level of anxiety and depression in the setting of a hospital medical outpatient clinic. The anxiety and depression subscales each have a range from 0-21, higher scores indicated higher levels of anxiety and depression, respectively. LOCF imputation was used for missing data. (NCT03255382)
Timeframe: Baseline, Week 16

Interventionunits on a scale (Least Squares Mean)
Fumaderm-1.8
Risankizumab-4.9

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Percentage of Participants Achieving 75% Improvement in PASI Score (PASI75) at Week 20

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data. (NCT03255382)
Timeframe: Week 20

Interventionpercentage of participants (Number)
Fumaderm38.3
Risankizumab95.0

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Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96

The number of Gd-enhancing lesions was assessed by using MRI scans. (NCT03870763)
Timeframe: Weeks 48 and 96

,,
Interventionnumber of lesions (Mean)
Week 48Week 96
Dimethyl Fumarate 240 mg00
Peginterferon Beta-1a 125 µg00.25
Placebo1.50.5

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Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96

The number of new or newly enlarging T2 hyperintense lesions that developed in each participant assessed on magnetic resonance imaging (MRI) scans. (NCT03870763)
Timeframe: Weeks 48 and 96

,,
Interventionnumber of lesions (Mean)
Week 48Week 96
Dimethyl Fumarate 240 mg0.52.5
Peginterferon Beta-1a 125 µg1.01.3
Placebo3.33.5

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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is 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. (NCT03870763)
Timeframe: Baseline up to Week 100

,,
InterventionParticipants (Count of Participants)
AEsSAEs
Dimethyl Fumarate 240 mg21
Peginterferon Beta-1a 125 µg60
Placebo31

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Annualized Relapse Rate

A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. The relapse rate for an individual participant was calculated as the number of relapses for that participant divided by the number of participant-years followed. The ARR for each enrolment group was calculated as the total number of relapses experienced in the group divided by the total number of participant-years on the study. An unadjusted relapse rate is reported. (NCT03870763)
Timeframe: Up to Week 96

Interventionrelapses per participant year (Number)
Dimethyl Fumarate 240 mg0.26
Peginterferon Beta-1a 125 µg0.00
Placebo0.46

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Time to First Relapse

A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. Time to relapse is defined as from the first dose of the study drug to the day of relapse. Time to First Relapse is estimated by Kaplan Mayer method. (NCT03870763)
Timeframe: Baseline up to Week 96

InterventionDays (Median)
Dimethyl Fumarate 240 mg413
Peginterferon Beta-1a 125 µgNA
Placebo166.5

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The Bioequivalent (BE) Comparison of AUC0-inf of Monomethyl Fumarate (MMF) Between Treatments

Pharmacokinetics: Plasma concentrations of MMF will be determined and used to calculate AUC0-inf MMF for each treatment. Venous blood samples were collected immediately prior to dosing (time 0), and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, and 24 hours postdose. (NCT04570670)
Timeframe: 24 hours

Interventionng*hr/mL (Geometric Mean)
Test (BLS-11)2984
Reference (Tecfidera)3116

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The BE Comparison of Cmax of Monomethyl Fumarate (MMF) Between Treatments

Pharmacokinetics: Plasma concentrations of MMF will be determined and used to calculate the Cmax of MMF for each treatment.Venous blood samples were collected immediately prior to dosing, and then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, and 24 hours postdose. (NCT04570670)
Timeframe: 24 hours

Interventionng/mL (Geometric Mean)
Test (BLS-11)1760
Reference (Tecfidera)1680

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