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. 2000;2000(2):CD001461.
doi: 10.1002/14651858.CD001461.

Azathioprine for rheumatoid arthritis

M E Suarez-Almazor  1 , C Spooner, E Belseck
Affiliations

Azathioprine for rheumatoid arthritis

M E Suarez-Almazor et al. Cochrane Database Syst Rev. 2000.

Update in

Abstract

Objectives: To assess the short-term effects of azathioprine for the treatment of rheumatoid arthritis (RA).

Search strategy: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including July 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search.

Selection criteria: All randomized controlled trials and controlled clinical trials comparing azathioprine against placebo in patients with rheumatoid arthritis.

Data collection and analysis: Data was extracted independently by two reviewers (CS, EB); disagreements were resolved by discussion or third party adjudication (MS). The same reviewers (CS, EB) assessed the methodological quality of the trials using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and functional status assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and for adverse reactions. The 95% confidence intervals (95% CI) are presented. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found.

Main results: Three trials with a total of 81 patients were included in the analysis. Forty patients were randomized to azathioprine and forty-one to placebo. A pooled estimate was calculated for two outcomes. A statistically significant benefit was observed for azathioprine when compared to placebo for tender joint scores. The standardized weighted mean difference between treatment and placebo was -0.98 (95% CI -1.45, -0.50). Withdrawals from adverse reactions were significantly higher in the azathioprine group OR=4.56 (95% CI 1.16, 17.85).

Reviewer's conclusions: Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.

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Conflict of interest statement

None known

Figures

1.1
1.1. Analysis
Comparison 1 Azathioprine vs. placebo ‐ Efficacy, Outcome 1 Joint scores and pain.
1.2
1.2. Analysis
Comparison 1 Azathioprine vs. placebo ‐ Efficacy, Outcome 2 Global assessment of efficacy and function.
1.3
1.3. Analysis
Comparison 1 Azathioprine vs. placebo ‐ Efficacy, Outcome 3 ESR.
2.1
2.1. Analysis
Comparison 2 Azathioprine vs. placebo ‐ Withdrawals and dropouts, Outcome 1 Withdrawals: global reasons.
2.2
2.2. Analysis
Comparison 2 Azathioprine vs. placebo ‐ Withdrawals and dropouts, Outcome 2 Withdrawals: specific adverse reactions.
3.1
3.1. Analysis
Comparison 3 Adverse reactions not requiring withdrawal, Outcome 1 Adverse reaction by specific system.
See this image and copyright information in PMC

References

References to studies included in this review

Levy 1972 {published data only}
    1. Levy J, Paulus HE, Barnett EV, Sokoloff M, Bangert R, & Pearson CM. A double‐blind controlled evaluation of azathioprine treatment in rheumatoid arthritis and psoriatic arthritis. Arthritis & Rheumatism 1972;15(1):116‐7.
Urowitz 1973 {published data only}
    1. Urowitz MB, Gordon DA, Smythe HA, Pruzanski W, & Ogryzlo MA. Azathioprine in rheumatoid arthritis. Arthritis & Rheum 1973;16:411‐418. - PubMed
Woodland 1981 {published data only}
    1. Woodland J, Chaput de Saintonge DM, Evans SJW, Sharman VL, & Currey HLF. Azathioprine in rheumatoid arthritis: double‐blind study of full versus half doses versus placebo. Ann Rheum Dis. 1981; Vol. 40:355‐359. - PMC - PubMed

References to studies excluded from this review

Barnes 1969 {published data only}
    1. Barnes CG, Currey JFD, Hazelman B, Mason RM, Strickland ID. Azathioprine: a controlled, double‐blind trial in rheumatoid arthritis. Ann Rheum Dis 1969;28:327‐8. - PMC - PubMed
Cade 1976 {published data only}
    1. Cade R, Stein G, Pickering M, Schlein E, Spooner G. Low dose, long term treatment of rheumatoid arthritis with azathioprine. Southern Medical Journal 1976;69(4):388‐392. - PubMed
De Silva 1981 {published data only}
    1. De Silva, Hazelman BL. Long‐term azathioprine in rheumatoid arthritis: a double‐blind study. Ann Rheum Dis 1981;40:560‐563. - PMC - PubMed
Dixon 1971 {published data only}
    1. Dixon A St J, Lindsay DJ, Collins EM. Immunosuppressive drugs in rheumatoid atrhritis. BMJ 1971;20:460. - PMC - PubMed
Goebel 1976 {published data only}
    1. Goebel KM, Janzen KJ, & Borngen U. Disparity between clinical and immune responses in a controlled trial of azathioprine in rheumatoid arthritis. Eur J Clin Pharmacol 1976;9:405‐410. - PubMed
Heurkens 1991 {published data only}
    1. Heurkens AHM, Westedt ML, Breedveld FC. Prednisone plus azathioprine treatment in patients with rheumatoid arthritis complicated by vasculitis. Arch Intern Med 1991;151:2249‐54. - PubMed
Levy 1975 {published data only}
    1. Levy J, Paulus HE, Bangert R. Comparison of azathioprine and cyclophosphamide in the treatment of rheumatoid arthritis. Arthritis & Rheum 1975;18:412‐413.
Mason 1969 {published data only}
    1. Mason M, Currey HLF, Barnes CG, Dunne JF, Hazleman BL, Strickland ID. Azathioprine in rheumatoid arthritis. Brit. Med. J 1969;1:420‐422. - PMC - PubMed
Nicholls 1973 {published data only}
    1. Nicholls A, Snaith ML, Maini RN, Scott JT. Proceedings: Controlled trial of azathioprine in rheumatoid vasculitis. Ann Rheum Dis 1973;32(6):589‐91. - PMC - PubMed
Pedersen 1984 {published data only}
    1. Pedersen BK, Beyer JM, Rasmussen A, Klarlund K, Horslev‐Petersen K, Pedersen BN, & Helin P. Azathioprine as single drug in the treatment of rheumatoid arthritis induces complete suppresion of natural killer cell activity. Acta Path Microbiol Immunol Scand 1984;Sect C 92:221‐225. - PubMed

Additional references

Clark 1998
    1. Clark P, Tugwell P, Bennet K, Bombardier C, Shea B, Wells G, Suarez‐Almazor ME. Meta‐analysis of injectable gold in rheumatoid arthritis. - PMC - PubMed
Dwosh 1977
    1. Dwosh IL, Stein HB, Urowitz MB, Smythe HA, Hunter T, Ogryzlo MA. Azathioprine in early rheumatoid arthritis. Comparison with gold and chloroquine. Arthritis Rheum 1977;20(2):685‐92. - PubMed
Felson 1993
    1. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993;36:729‐40. - PubMed
Halberg 1984
    1. Halberg P, Bentzon MW, Crohn O, et al. Double‐blind trial of levamisole, penicillamine and azathioprine in rheumatoid arthritis. Danish Med Bull 1984;31:403‐9. - PubMed
Jadad 1996
    1. Jadad A, Moore A, Carrol D, et al. Assessing the quality of reports of randomized trials: is blinding necessary?. Control Clin Trial 1996;17:1‐12. - PubMed
Jeurissen 1991
    1. Jeurissen MEC, Boerbooms AMTh, Putte LBA, Doesburg WH, Lemmens A. Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. Arandomized double‐blind study. Ann Int Med 1991;114:999‐1004. - PubMed
Kazis 1989
    1. Kazis LEE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. Medical Care 1989;27(S3):S178‐89. - PubMed
OMERACT 1993
    1. OMERACT. Conference on Outcome Measures in Rheumatoid Arthritis Clinical Trials. J Rheumatol 1993;20:526‐91. - PubMed
Paulus 1984
    1. Paulus HE, Williams HJ, Ward JR, et al. Azathioprine versus d‐penicillamine in rheumatoid arthritis patients who have been treated unsuccesfully with gold. Arthritis Rheum 1984;27:721‐7. - PubMed
Singh 1989
    1. Singh G, Fries JF, Spitz PW, Williams CA. Azathioprine toxicity in rheumatoid arthritis: a national post‐marketing perspective. Arthritis Rheum 1989:a national post‐marketing perspective. Arthritis Rheum 1989;837‐43. - PubMed
Suarez‐Almazor 1998a
    1. Suarez‐Almazor ME, Belseck E, Shea B, Homik J, Wells G, Tugwell P. Rheumatoid arthritis: Antimalarials for treating rheumatoid arthritis. Cochrane Data Base of Systematic Reviews 1998, Oxford, UK. - PubMed
Suarez‐Almazor 1998b
    1. Suarez‐Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. Rheumatoid arthritis: Cyclophosphamide for treating rheumatoid arthritis. Cochrane Data Base of Systematic Reviews 1998, Oxford, UK. - PubMed
Suarez‐Almazor 1998d
    1. uarez‐Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. Rheumatoid arthritis: Sulfasalazine for treating rheumatoid arthritis. Cochrane Data Base of Systematic Reviews 1998, Oxford, UK. - PMC - PubMed
Suarez‐Almazor 1999c
    1. Suarez‐Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. Rheumatoid arthritis: Methotrexate vs. placebo [Methotrexate for treating rheumatoid arthritis]. Cochrane Data Base of Systematic Reviews 1999, Oxford, UK.
Wells 1998
    1. Wells G, Haguenauer D, Shea B, Suarez‐Almazor ME, Welch VA, Tugwell. Rheumatoid Arthritis (RA): A meta‐analysis of cyclosporine in rheumatoid arthritis [Cyclosporine for treating rheumatoid arthritis]. Cochrane Data Base of Systematic Reviews 1998, Oxford, UK. - PMC - PubMed
Whisnant 1982
    1. Whisnant JK, Pelkey J. Rheumatoid arthritis: treatment with azathioprine (Imuran). Clinical side effects and laboratory abnormalities. Ann Rheum Dis 1982;41(Suppl 1):44‐2. - PMC - PubMed

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