Penicillamine for treating rheumatoid arthritis

Penicillamine is a penicillin derived compound. Studies showed that this could be used to treat rheumatoid arthritis originally in 1950. It was frequently used in the past, but its use has declined with the increasing use of other disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate. The purpose of this summary was to find out if penicillamine is helpful in the treatment of rheumatoid arthritis.

Penicillamine was seen to be beneficial for all ranges of dosages for disease activity on tender joint pain, physician global assessment and sed rate. No major differences were observed between placebo and low dose penicillamine (<500 mg/day). For higher dosages, patients on penicillamine were twice as likely to withdraw than those receiving placebo 500 to <1000 mg/day. D-penicillamine appears be have a clinical and statistical benefit on the disease activity of patients with rheumatoid arthritis. Its benefit is similar to that of other such drugs, such as disease modifying anti-rheumatic drugs (DMARDs). More adverse reactions are seen in patients being treated with D-penicillamine.

Authors' conclusions: 

D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.

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Background: 

D-penicillamine is a penicillin derived compound originally used to treat patients with rheumatoid arthritis (RA) in the 1950's. Although frequently used in the past, its use has declined with the increasing use of other disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate.

Objectives: 

To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA).

Search strategy: 

We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000) and Medline up to and including August 2000 and Embase from 1988-2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search.

Selection criteria: 

All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis.

Data collection and analysis: 

The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. 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: 

Six trials were identified, with 425 patients randomized to D-penicillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0.51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0.87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities.

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