mercaptopurine and Arthritis--Rheumatoid

Preoperative immunosuppressive use among patients with Crohn's disease or ulcerative colitis may lead to an increased risk of postoperative complications. There is limited information on the preoperative safety profile of methotrexate (MTX) in inflammatory bowel disease (IBD).. A retrospective study of patients who underwent abdominal surgery for IBD between 1993 and 2012 was performed and records abstracted, including preoperative use of MTX, azathioprine/6-mercaptopurine, antitumor necrosis factor, and corticosteroids. Early postoperative complications, including death, septic, and nonseptic complications were identified. A meta-analysis was also performed on the use of preoperative MTX in patients with IBD or rheumatoid arthritis.. A total of 180 patients with IBD underwent abdominal surgery. A total of 15 patients received MTX either monotherapy or in combination therapy. Total early postoperative complications were identified in 71 (39%) patients, specifically 5 patients on oral MTX. A total of 51 cases (28%) of septic complications and 20 (11%) nonseptic. No significant association between the use of MTX and early postoperative complications was found. The odds ratio (OR) of complications versus no complications associated with MTX was 0.75 (95% CI, 0.25-2.29) and with azathioprine/6-mercaptopurine, OR 1.48 (95% CI, 0.77-2.84). The odds of a septic complication associated with MTX were 0.58 (95% CI, 0.09-3.73), and higher in azathioprine/6-mercaptopurine, OR 3.97 (95% CI, 1.03-15.3). Our meta-analysis also did not reveal an increased risk of postoperative complications in IBD or rheumatoid arthritis on preoperative MTX (OR 0.62, 95% CI, 0.34-1.15).. Preoperative MTX use does not seem to be associated with early postoperative complications in IBD.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Azathioprine; Colitis, Ulcerative; Crohn Disease; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Middle Aged; Odds Ratio; Postoperative Complications; Preoperative Period; Retrospective Studies; Sepsis; Tumor Necrosis Factor-alpha; Young Adult

Azathioprine (AZA) is widely used in the management of rheumatological diseases. Despite its efficacy, AZA can often cause bone marrow suppression, notably leucopenia, which has been recorded in up to 17% of patients taking AZA for rheumatoid arthritis, though this can be considered clinically significant in about 3% overall. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism. TPMT status can be assessed prior to AZA treatment by measuring enzyme activity or genotyping techniques. Analysis of recent data suggests that by optimizing the AZA dose on the basis of TPMT status testing (with a substantial reduction in dose for patients homozygous for mutant TPMT alleles), a reduction in drug-induced morbidity and cost savings can be made by avoiding hospitalization and rescue therapy for leucopenic events. In this article we review the pharmacogenetic and clinical implications of the TPMT polymorphism, emphasizing its relevance to rheumatologists managing diseases with AZA.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Biomarkers; Erythrocytes; Genotype; Humans; Leukopenia; Mercaptopurine; Methyltransferases; Pharmacogenetics; Polymorphism, Genetic

Topics: Adolescent; Adrenal Cortex Hormones; Alkylating Agents; Anemia; Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Antilymphocyte Serum; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Colchicine; Cyclosporins; Danazol; Female; Hepatitis, Chronic; Humans; Immunoglobulin G; Immunosuppressive Agents; Levamisole; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Multiple Sclerosis; Pregnancy

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.

Topics: Acute Kidney Injury; Anemia, Aplastic; Antilymphocyte Serum; Arthritis, Rheumatoid; Blood Cell Count; Blood Transfusion; Cyclophosphamide; Deficiency Diseases; Erythropoietin; Humans; Immune System Diseases; Infections; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisone; Remission, Spontaneous; Splenectomy; Thymoma; Thymus Neoplasms

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Chlorambucil; Cyclophosphamide; Granulomatosis with Polyangiitis; Hepatitis; Humans; Immunosuppressive Agents; Liver Cirrhosis; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Mice; Mice, Inbred NZB; Multiple Sclerosis; Nephritis; Nephrosis; Nitrogen Mustard Compounds; Penicillins; Psoriasis; Uveitis, Anterior

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Colitis, Ulcerative; Crohn Disease; Cyclophosphamide; Granulomatosis with Polyangiitis; Hepatitis; Humans; Immune Complex Diseases; Immunosuppressive Agents; Infections; Liver Cirrhosis, Biliary; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Nephrotic Syndrome; Ophthalmia, Sympathetic; Psoriasis; Thioguanine; Uveitis

Topics: Alkylating Agents; Anemia, Hemolytic, Autoimmune; Antibodies; Antimetabolites; Arthritis, Rheumatoid; Azathioprine; Blood Coagulation Disorders; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Cyclophosphamide; Dermatomyositis; Factor VIII; Hepatitis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Prednisolone; Purpura, Thrombocytopenic; Scleroderma, Systemic

Topics: Adrenocorticotropic Hormone; Aminopterin; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Penicillamine

Topics: Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Penicillamine

Topics: Alopecia; Aminopterin; Antimetabolites; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Cystitis; Female; Herpes Zoster; Humans; Jaundice; Mechlorethamine; Mercaptopurine; Methotrexate

Topics: Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Collagen Diseases; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Spondylitis, Ankylosing; Thiotepa; Triaziquone

Topics: Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Mechlorethamine; Mercaptopurine; Methotrexate; Prednisolone; Pregnancy

Topics: Aged; Antimetabolites; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Kinetics; Mercaptopurine; Middle Aged

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclophosphamide; Drug Administration Schedule; Drug Therapy, Combination; Glucocorticoids; Humans; Immunity; Mercaptopurine; Penicillamine

Topics: Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Evaluation Studies as Topic; Germany, East; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Procarbazine; Triaziquone

Topics: Alkylating Agents; Anemia, Hemolytic, Autoimmune; Antibodies; Antimetabolites; Arthritis, Rheumatoid; Azathioprine; Blood Coagulation Disorders; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Cyclophosphamide; Dermatomyositis; Factor VIII; Hepatitis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Prednisolone; Purpura, Thrombocytopenic; Scleroderma, Systemic

Topics: Adrenocorticotropic Hormone; Aminopterin; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Penicillamine

Topics: Alopecia; Aminopterin; Antimetabolites; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Cystitis; Female; Herpes Zoster; Humans; Jaundice; Mechlorethamine; Mercaptopurine; Methotrexate

Ras-related C3 botulinum substrate 1 (Rac1) is a member of the small molecule family Rho guanosine triphosphate (GTP)ases. Recent findings reveal epigenetic downregulation of Rac1 is a mechanism of depression.. The purpose of this study was to evaluate Rac1 as a therapeutic target for depression we examine the association between thiopurines, which inhibit Rac1, and the risk of depression among US veterans.. This study uses data spanning January 2000-May 2019, comparing thiopurine exposure (no exposure, less than one year, 1-2.9 years, 3-5 years, and greater than five years) in two separate cohorts, a rheumatoid arthritis cohort and inflammatory bowel disease cohort. We estimate the hazard of depression using a time dependent cox proportional hazards model.. A total of 76,763 rheumatoid arthritis and 46,787 inflammatory bowel disease patients met all inclusion criteria. Patients exposed to thiopurines less than one year have a 27% (hazard ratio=1.272; 95% confidence interval=(1.038-1.559)) and 67% (hazard ratio=1.667 95% confidence interval=(1.501-1.850)) higher risk of depression in the rheumatoid arthritis and inflammatory bowel disease cohorts, respectively. In the inflammatory bowel disease cohort, we find the risk of depression is increased for up to five years of thiopurine exposure.. These results provide evidence that Rac1 regulation is a viable therapeutic target for depression. Further research into therapeutics targeting Rac1 for the treatment of depression is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Cohort Studies; Depression; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Mercaptopurine; Middle Aged; rac1 GTP-Binding Protein; Retrospective Studies; Veterans

Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.. Odds ratio (OR) assessment for AID-directed therapies.. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.. In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Case-Control Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Incidence; Leukemia, Myeloid, Acute; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Mycophenolic Acid; Myelodysplastic Syndromes; Odds Ratio; Psoriasis; Retrospective Studies; Risk Factors; United States

Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune-mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti-tumor necrosis factor (anti-TNF).. Three retrospective cohort studies within Medicare (2000-2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti-TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy.. Across all medication groups, 107 women experienced breast cancer recurrence during 5,196 person-years. The incidence rates were 20.3 and 19.6 per 1,000 person-years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti-TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67-1.69), anti-TNF therapy (HR 1.13, 95% CI 0.65-1.97), or thiopurines (HR 2.10, 95% CI 0.62-7.14).. The risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti-TNF therapy was not statistically significantly increased, although we cannot rule out a 2-fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti-TNF therapy in RA or IBD patients with treated breast cancer.

Topics: Adalimumab; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Azathioprine; Breast Neoplasms; Cohort Studies; Etanercept; Female; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Infliximab; Medicare; Mercaptopurine; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Proportional Hazards Models; Retrospective Studies; Risk Factors; Tumor Necrosis Factor-alpha; United States

The risk of non-Hodgkin's lymphoma (NHL) with tumor necrosis factor alpha (TNF-α) inhibitors is unclear, whether related to concomitant thiopurines usage or due to the underlying inflammatory disease. We sought to review all cases of T-cell NHL reported to the Food and Drug Administration (FDA) in patients receiving TNF-α inhibitors for all approved indications and examine the risk of T-cell NHL with TNF-α inhibitors in comparison with the use of thiopurines in inflammatory bowel disease (IBD).. The FDA Adverse Event Reporting System (AERS) was queried for all lymphomas following treatment with the following TNF-α inhibitors: infliximab, adalimumab, certolizumab, etanercept, and their trade names. Full reports for T-cell NHL cases were identified using the Freedom of Information Act. In addition, T-cell NHL reported in patients IBD with the use of the thiopurines-azathioprine, 6-mercaptopurine, and their trade names were also collected. A search of MEDLINE was performed for additional T-cell NHL with TNF-α inhibitors or thiopurines, not reported to the FDA but available in published literature. The histological subtypes of T-cell NHL reported with TNF-α inhibitors were compared with reported subtypes in Surveillance Epidemiology and End Results (SEER) -17 registry. Reported risk of T-cell NHL in IBD with TNF-α inhibitors, thiopurines, or concomitant use was calculated using Fisher's exact test using 5-aminosalicylates as control drugs.. A total of 3,130,267 reports were downloaded from the FDA AERS (2003-2010). Ninety-one cases of T-cell NHL with TNF-α inhibitors were identified in the FDA AERS and nine additional cases were identified on MEDLINE search. A total of 38 patients had rheumatoid arthritis, 36 cases had Crohn's disease, 11 had psoriasis, 9 had ulcerative colitis, and 6 had ankylosing spondylitis. Sixty-eight of the cases (68%) involved exposure to both a TNF-α inhibitor and an immunomodulator (azathioprine, 6-mercaptopurine, methotrexate, leflunomide, or cyclosporine). Hepatosplenic T-cell lymphoma (HSTCL) was the most common reported subtype, whereas mycosis fungoides/Sezary syndrome and HSTCL were identified as more common with TNF-α-inhibitor exposure compared with SEER-17 registry. Nineteen cases of T-cell NHL with thiopurines were identified in the FDA AERS and one additional case on MEDLINE. Reported risk of T-cell NHL was higher with TNF-α inhibitor use in combination with thiopurines (95% confidence interval (CI) 4.98-354.09; P<0.0001) and thiopurines alone (95% CI 8.32-945.38; P<0.0001) but not with TNF-α inhibitor use alone (95% CI 0.13-10.61; P=1.00).. Risk of T-cell NHL is increased with TNF-α inhibitor use in combination with thiopurines but not with TNF-α inhibitors alone.

Topics: Adalimumab; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Azathioprine; Certolizumab Pegol; Drug Therapy, Combination; Etanercept; Female; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Lymphoma, T-Cell; Male; MEDLINE; Mercaptopurine; Middle Aged; Odds Ratio; Polyethylene Glycols; Psoriasis; Receptors, Tumor Necrosis Factor; Risk Factors; SEER Program; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha; United States; United States Food and Drug Administration

Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA. Patients with heterozygous deficiency have 50% of enzyme activity and have been shown to respond well and tolerate half a standard dose. We describe a patient with homozygous deficiency of TPMT who developed life threatening neutropenic sepsis, and advocate that all patients should be tested for TPMT activity prior to starting AZA therapy.

Topics: Aged; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Diagnostic Tests, Routine; Female; Homozygote; Humans; Immunosuppressive Agents; Inactivation, Metabolic; Mercaptopurine; Methylation; Methyltransferases; Neutropenia; Prodrugs; Sepsis; United Kingdom

Topics: 5'-Nucleotidase; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Cross-Sectional Studies; Humans; Hypoxanthine Phosphoribosyltransferase; Immunoglobulin M; Lupus Erythematosus, Systemic; Mercaptopurine; Methyltransferases; Reference Values; Rheumatoid Factor

Two specific high-performance liquid chromatography methods for determining plasma concentrations of azathioprine and 6-mercaptopurine after oral administration of azathioprine are presented. It was shown that azathioprine is unstable in the blood samples unless immediately cooled in ice water. The 2-amino analog, guaneran, was used as internal standard for azathioprine, which was extracted from plasma with ethylacetate. A Nucleosil C18 column was used for the separation. The detection limit was 6 nM. For quantification of 6-mercaptopurine, 6-thioguanine was used as internal standard. Plasma was deproteinized with HClO4 and the sample was purified on mercurial cellulose. A Beckman ODS column was used and the detection limit was 5 nM. Pharmacokinetic data from two patients are presented. Unchanged azathioprine was seen until 6 h after an oral dose of 32 mg/m2.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Azathioprine; Caffeine; Drug Stability; Female; Humans; Mercaptopurine; Middle Aged

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Topics: Acute Disease; Arthritis, Rheumatoid; Azathioprine; Carcinogens; Chlorambucil; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Pancytopenia; Time Factors

Natural killer (NK) cell activity against K562 target cells was studied in six patients with definite or classical rheumatoid arthritis before and during treatment with azathioprine. Azathioprine induced suppression of NK cell activity, but treatment with azathioprine for 5-8 months was necessary before NK cell activity was completely suppressed. In vitro incubation of mononuclear cells from a healthy donor with azathioprine or 6-mercaptopurine in concentrations not reducing cell viability did not inhibit NK cell activity, nor did sera from patients treated with azathioprine for more than 6 months.

Topics: Adult; Arthritis, Rheumatoid; Azathioprine; Female; Humans; Immunosuppression Therapy; In Vitro Techniques; Interferon Type I; Killer Cells, Natural; Male; Mercaptopurine; Middle Aged; Time Factors

Methotrexate (MTX) appears to be useful in patients with rheumatoid arthritis (RA) refractory to other drugs but its long-term toxicity and efficacy are uncertain. A retrospective study of MTX in such patients in comparison with the purine analogues, azathioprine and 6-mercaptopurine was made using life-table analysis. Eighty-four patients took MTX in a median dose of 7.5 mg/week whilst 55 received purine analogues, 100 mg/day (median). By 12 months, 19.3% of patients had ceased MTX due to toxicity, compared with 29.3% for purine analogues. Toxicity severe enough to warrant stopping therapy was uncommon after 8 months with either drug. At 12 months 61.5% of the MTX patients had achieved defined criteria of improvement compared with 25.6% for the purine analogues (p less than 0.05). The number of patients improving on purine analogues did not increase substantially after 6 months, whereas the number improving with MTX continued to 12 months. MTX in a low-dose regimen is useful in refractory RA and superior to low-dose purine analogues.

Topics: Actuarial Analysis; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Azathioprine; Female; Humans; Male; Mercaptopurine; Methotrexate; Middle Aged

Topics: Adult; Aged; Arthritis, Rheumatoid; Azathioprine; Blood Sedimentation; Female; Follow-Up Studies; Humans; Male; Mercaptopurine; Middle Aged; Psoriasis; Scleroderma, Localized

Topics: Adult; Antibodies; Antineoplastic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Chlorambucil; Cyclophosphamide; Humans; Hypersensitivity, Delayed; Lymphocytes; Mercaptopurine; Middle Aged; Neutrophils; Rheumatoid Factor; Thiotepa

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Azathioprine; Carrageenan; Connective Tissue; Connective Tissue Cells; Cyclophosphamide; Edema; Female; Hydrocortisone; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Mycobacterium; Rats; Time Factors

Topics: Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Azathioprine; Biological Assay; Cyclophosphamide; Dexamethasone; Disease Models, Animal; Drug Evaluation, Preclinical; Freund's Adjuvant; Hexobarbital; Humans; Hydroxylation; Inflammation; Irritants; Male; Mercaptopurine; Microsomes, Liver; Rats; Rats, Inbred Lew; Sleep; Time Factors

Topics: Aminocaproates; Animals; Anti-Inflammatory Agents; Antibody Formation; Antibody-Producing Cells; Arthritis, Rheumatoid; Central Nervous System; Dermatitis, Contact; Erythrocytes; Ethanolamines; Hemolysin Proteins; Immunosuppression Therapy; Leukocytes; Mercaptopurine; Mice; ortho-Aminobenzoates; Protease Inhibitors; Purines; Skin Transplantation; Transplantation Immunology; Transplantation, Homologous

Topics: Antigen-Antibody Complex; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Informed Consent; Male; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Rheumatoid Factor; Synovial Membrane; Thiotepa

Topics: Anemia, Hemolytic, Autoimmune; Antigen-Antibody Reactions; Arthritis, Rheumatoid; Azathioprine; Crohn Disease; Cyclophosphamide; Female; Glomerulonephritis; Glucocorticoids; Hepatitis; Humans; Immunity; Immunity, Cellular; Immunosuppression Therapy; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Nephrotic Syndrome; Purpura, Thrombocytopenic

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Azathioprine; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged

Topics: Adult; Aged; Antineoplastic Agents; Arthritis, Rheumatoid; Chlorambucil; Cyclophosphamide; Female; Humans; Male; Mercaptopurine; Middle Aged

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Antimetabolites; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Female; Humans; Immunosuppressive Agents; Long-Term Care; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged; Purpura, Thrombocytopenic

Topics: Antibody Formation; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Cyclophosphamide; Ethylamines; Humans; Immunity, Cellular; Immunosuppression Therapy; Mercaptopurine; Oxazines; Phosphorus Acids; Skin Tests

Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Antibody Formation; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Immunosuppressive Agents; Liver; Liver Function Tests; Lupus Erythematosus, Systemic; Lymphocyte Activation; Mercaptopurine; Middle Aged; Time Factors

Topics: Arthritis, Rheumatoid; Azathioprine; Blood Sedimentation; Chlorambucil; Cyclophosphamide; Humans; Immunoelectrophoresis; Immunosuppressive Agents; Lymphocyte Activation; Mercaptopurine; Methotrexate; Rheumatoid Factor; Skin Manifestations; Statistics as Topic

Topics: Animals; Arthritis, Rheumatoid; Cyclophosphamide; DNA; Humans; Lymphocyte Activation; Mercaptopurine; Mice; Mice, Inbred AKR; Tritium

Topics: Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Chronic Disease; Collagen Diseases; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Phytotherapy; Plants, Medicinal; Plants, Toxic; Podophyllum; Prednisolone; Spondylitis, Ankylosing; Thiotepa; Triaziquone

Topics: Arthritis, Rheumatoid; Azathioprine; Collagen Diseases; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Thioguanine

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Arthritis, Rheumatoid; Azathioprine; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Lectins; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocytes; Male; Mercaptopurine; Middle Aged; Purpura, Thrombocytopenic; Streptolysins

Topics: Antigen-Antibody Reactions; Arthritis, Rheumatoid; Basement Membrane; Biopsy; Drug Hypersensitivity; Female; Glomerulonephritis; Gold; Humans; Kidney; Mercaptopurine; Microscopy, Electron; Middle Aged; Prednisolone

Topics: Adult; Arthritis, Rheumatoid; Azathioprine; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocytes; Mercaptopurine; Middle Aged

Topics: Alanine Transaminase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Chronic Disease; Hepatitis; Humans; Liver Function Tests; Male; Mercaptopurine; Middle Aged

Topics: Adult; Aged; Arthritis, Rheumatoid; Azathioprine; Culture Techniques; Humans; Immunosuppressive Agents; Lectins; Leukocyte Count; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocytes; Mercaptopurine; Middle Aged; Stimulation, Chemical; Streptolysins

Topics: Adolescent; Antimetabolites; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Betamethasone; Chronic Disease; Humans; Male; Mercaptopurine; Methotrexate; Middle Aged; Synovitis; Thiotepa

Topics: Antimetabolites; Arthritis, Rheumatoid; Azathioprine; Chronic Disease; Feeding and Eating Disorders; Humans; Mercaptopurine; Methotrexate; Nausea; Time Factors

Topics: Adolescent; Arthritis, Rheumatoid; Child; Child, Preschool; Female; Humans; Male; Mercaptopurine

Topics: Adrenal Cortex Hormones; Adult; Aged; Anemia, Hemolytic, Autoimmune; Arthritis, Rheumatoid; Asthma; Azathioprine; Collagen Diseases; Female; Humans; Leukopenia; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged; Polyarteritis Nodosa; Polymyalgia Rheumatica; Thyroiditis

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Mercaptopurine