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Azathioprine for treating rheumatoid arthritis

  • Review
  • Intervention


  • Maria E Suarez-Almazor,

    Corresponding author
    1. The University of Texas, M.D. Anderson Cancer Center, General Internal Medicine, Ambulatory Treatment and Emergency Care, Houston, Texas, USA
    • Maria E Suarez-Almazor, General Internal Medicine, Ambulatory Treatment and Emergency Care, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 437, Houston, Texas, 77030, USA.

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  • Carol Spooner,

    1. 1G1.52 Walter Mackenzie Health Centre, Division of Emergency Medicine, Edmonton, Alberta, Canada
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  • Elaine Belseck

    1. University of Alberta, Department of Pediatrics, Alberta, Canada
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Azathioprine is a purine analogue with immunosuppressive properties. Although several trials have reported a beneficial effect in patients with rheumatoid arthritis (RA), because of concerns over its safety it is generally used only in severe RA.


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

Search methods

We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline up to and including August 2000 and Embase from 1988 to August 2000. We also conducted 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).

Authors' 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.



Azathioprine 治療類風濕性關節炎





搜尋包括Cochrane Musculoskeletal Group's trials register, Cochrane Controlled Trials Register (issue 3, 2000) and MEDLINE (直到2000年8月)及EMBASE 19882000。同時手動搜尋所選文章之參考文獻。




兩位作者獨立進行資料摘錄,不一致處由討論或第三者決定。每篇試驗研究的品質由兩位作者獨立使用驗證過的方法品質評估工具進行評估。類風濕性關節炎病人之結果測量為6個月終點指標。以標準化平均差異(standardized mean difference)做關節數,疼痛及功能狀態評估。紅血球沈降速率以加權平均差異做評估。毒性則以退出治療及副作用之勝算比為評估指標。使用卡方檢定看各試驗間的異質性,因無統計上異質性,因此以固定效應模型(fixedeffects model)分析。


3個研究共81例包含於分析中,40例病患使用Azathioprine藥物,41例病患使用安慰劑。Azathioprine藥物比安慰劑療效在減少疼痛的關節數目有統計上顯著差異,標準化加權平均差異是 −0.98 (95% CI介於 −1.45 to 0.50)之間。因副作用而退出使用在Azathioprine組高於安慰劑組,其勝算比為4.56 (95% C.I. 1.16∼17.85)。





此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。



Plain language summary

Azathioprine for treating rheumatoid arthritis

Azathioprine is a drug that suppresses the immune system. This review includes three trials with a total of 81 patients. Forty patients were given azathioprine and forty-one were given placebo. Patients taking azathioprine had lower tender joint scores when compared to patients taking placebo. Significantly more patients in the azathioprine group withdrew from the studies due to adverse reactions compared to patients in the placebo group.

This evidence is based on a small number of patients in older trials. These findings suggest that several other drugs should be used before considering azathioprine for a patient with rheumatoid arthritis.