Cyclophosphamide for treating rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

The use of immunosuppressive drugs for the treatment of RA has been advocated for decades. Cyclophosphamide is an antineoplastic agent widely used in the treatment of cancer patients. It is an alkylating drug, with a marked cytotoxic effect on mononuclear cells and other leukocytes.

Objectives

To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis.

Search methods

We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), MEDLINE and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search.

Selection criteria

All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis.

Data collection and analysis

Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout.

Main results

A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57).

Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections.

Authors' conclusions

Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.

摘要

背景

Cyclophosphamide治療類風濕性關節炎

Cyclophosphamide用於治療癌症及治療類風濕性關節炎已有數十年歷史。

目標

本文評估Cyclophosphamide在治療類風濕性關節炎的短期療效。

搜尋策略

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

選擇標準

所有比較Cyclophosphamide與安慰劑﹝或使用另一種被認為未達有效治療劑量的藥物﹞於類風濕性關節炎病人之隨機對照及控制對照臨床研究。

資料收集與分析

兩位作者獨立進行資料摘錄。每篇試驗研究的品質由兩位作者獨立使用驗證過的品質評估工具﹝Jadad分數﹞進行評估。類風濕性關節炎病人之結果測量為試驗之起始與終點之差異。使用標準化平均差異分析關節數目。使用加權平均差異分析紅血球沉降速率。副作用分析則計算病患停止使用的勝算比 (OR)。本文使用卡方檢定各試驗間異質性,並用固定效應模型(fixedeffects model)分析。

主要結論

2個研究包含70例病患於分析中,31例病患使用Cyclophosphamide。Cyclophosphamide比安慰劑組之疼痛及腫脹關節數目的標準化差異分別為 −0.57 及 −0.59。Cyclophosphamide比安慰劑組之紅血球沉降速率也較多,但未達統計上顯著差異(−12 mm, 95%CI: −26 to 2.5)。有1篇報告顯示新或更加骨侵蝕勝算比為0.17 (95% CI: 0.05 to 0.57)。安慰劑組因無效而退出為Cyclophosphamide組6倍。因副作用而退出在Cyclophosphamide組較多(Odds ratio = 2.9),包括出血性膀胱炎、噁心、嘔吐、白血球偏低、血小板降低、無月經及帶狀?疹感染。

作者結論

Cyclophosphamide在類風濕性關節炎治療有臨床上及統計上助益,與其他修飾病程抗風濕藥物(DMARD)如抗瘧疾藥物或Sulfasalazine相似,但比methotrexate低。另外毒性較嚴重,與其他抗風濕藥物效益─風險比低,限制其使用性。

翻譯人

本摘要由林口長庚醫院余光輝翻譯。

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

總結

無總結

Plain language summary

Cyclophosphamide for treating rheumatoid arthritis

This review included 31 patients taking cyclophosphamide and 39 patients taking placebo. Patients taking cyclophosphamide had improved tender and swollen joint scores. Patients receiving placebo were six times more likely to discontinue treatment because of lack of treatment effect than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections.

Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. But due to serious side effects, its use should remain limited to patients who have failed treatment with various other therapies.