TY - JOUR
T1 - Penicillamine for treating rheumatoid arthritis
AU - Suarez-Almazor, Maria E.
AU - Belseck, Elaine
AU - Spooner, Carol
N1 - Funding Information:
The reviewers would like to acknowledge Dr. Ann Cranney and Dr. Dan Furst for their comments and suggestions, as well as the editors of the Cochrane Musculoskeletal Group for their editorial comments.
Publisher Copyright:
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PY - 2000/10/23
Y1 - 2000/10/23
N2 - 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 methods: 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. 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.
AB - 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 methods: 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. 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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U2 - 10.1002/14651858.CD001460
DO - 10.1002/14651858.CD001460
M3 - Article
C2 - 10796440
AN - SCOPUS:84921431202
SN - 1465-1858
VL - 2011
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
IS - 10
M1 - CD001460
ER -