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. 2000;2000(2):CD001157.
doi: 10.1002/14651858.CD001157.

Cyclophosphamide for rheumatoid arthritis

M E Suarez-Almazor  1 , E Belseck, B Shea, G Wells, P Tugwell
Affiliations

Cyclophosphamide for rheumatoid arthritis

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

Update in

  • Cyclophosphamide for treating rheumatoid arthritis.
    Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. Suarez-Almazor ME, et al. Cochrane Database Syst Rev. 2000;(4):CD001157. doi: 10.1002/14651858.CD001157. Cochrane Database Syst Rev. 2000. PMID: 11034702

Abstract

Objectives: To estimate the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis.

Search strategy: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. 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 Jadad's scale (Jadad 1995) 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.

Reviewer's 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.

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Conflict of interest statement

None known

Figures

1.1
1.1. Analysis
Comparison 1 Cyclophosphamide vs. placebo ‐ Efficacy, Outcome 1 Tender joints per patient.
1.2
1.2. Analysis
Comparison 1 Cyclophosphamide vs. placebo ‐ Efficacy, Outcome 2 Swollen joints per patient.
1.3
1.3. Analysis
Comparison 1 Cyclophosphamide vs. placebo ‐ Efficacy, Outcome 3 ESR.
1.4
1.4. Analysis
Comparison 1 Cyclophosphamide vs. placebo ‐ Efficacy, Outcome 4 Radiolological damage ‐ Patients with new/worse erosions.
2.1
2.1. Analysis
Comparison 2 Cyclophosphamide vs. placebo ‐ Withdrawals and dropouts, Outcome 1 Withdrawals and dropouts ‐ Total.
2.2
2.2. Analysis
Comparison 2 Cyclophosphamide vs. placebo ‐ Withdrawals and dropouts, Outcome 2 Withdrawals due to inefficacy.
2.3
2.3. Analysis
Comparison 2 Cyclophosphamide vs. placebo ‐ Withdrawals and dropouts, Outcome 3 Withdrawals due to adverse reactions.
See this image and copyright information in PMC

References

References to studies included in this review

CCC 1970 {published data only}
    1. CCC. Cooperating Clinics Committee of the American Rheumatism Association. A controlled trial of cyclophosphamide in rheumatoid arthritis. N Engl J Med 1970;283(17):883‐9. - PubMed
Townes 1976 {published data only}
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References to studies excluded from this review

Fries 1970 {published data only}
    1. Fries JF, Sharp GC and, McDevitt HO Holman HR. A controlled trial of cyclophosphamide therapy in connective tissue disease. Arthritis Rheum 1970;3:316‐317.
Lidsky 1973 {published data only}
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