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Penicillamine for treating rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

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.

摘要

背景

Penicillamine 治療類風濕性關節炎

Penicillamine是penicillin衍生物製劑,雖然於1950年代常用於治療類風濕性關節炎,但其它修飾病程抗風濕藥物(DMARD)如Methotrexate增加使用後,其使用量已減少。

目標

評估Penicillamine在治療類風濕性關節炎的短期效果。

搜尋策略

2002年2月25日利用「‘Lewy body’、‘Lewy bodies‘和‘Lewy’」等關鍵字針對Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫進行檢索,這個資料庫包含了所有主要健康照護資料庫和試驗資料庫中的資料,並且會進行定期性的更新。

選擇標準

所有比較Penicillamine與安慰劑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

每篇試驗研究的品質由兩位作者使用經效度驗證過之品質評估工具﹝Jadad 1996﹞獨立評估,並由第三位作者驗證。。類風濕性關節炎病人之結果測量為6個月終點指標,並依Dpenicillamine使用的劑量: 低 (小於500 毫克/天),中 (500 到1000毫克/天) ,及高劑量 (大於或等於1000毫克/天)做分層分析。一位作者擷取數據,並由另一位作者檢查。以標準化加權平均差異(standardized mean difference)做腫脹的關節數,疼痛及總體評估。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。本文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。

主要結論

6個研究包含於分析中,425例病患使用Penicillamine藥物,258例病患使用安慰劑。DPenicillamine藥物三種劑量比安慰劑療效在多種指標包括腫脹的關節數,疼痛及醫師總體評估及紅血球沈降速率上有統計上顯著差異。 在中劑量 (500 到1000毫克/天)與安慰劑,腫脹的關節數標準化平均差異是 −0.51 (介於 −0.88 to −0.14)之間,疼痛標準化平均差異是 −0.56 (介於 −0.87 to −0.26)之間,在醫師總體評估是 −0.97 (介於 −1.25 to −0.70)。紅血球沉降速率差異是 −10.6 mm/hr。高劑量組也有相似結果。副作用在高劑量及中劑量Dpenicillamine組較高 (OR分別為1.63 及 2.13),主要是腎臟及血液的副作用反應增加 (OR分別為2.60 及 4.95)。

作者結論

Penicillamine治療類風濕性關節炎疾病活性有臨床及統計上顯著差異。其效果與其它修飾病程抗風濕藥物(DMARD)相似,但Penicillamine副作用較多。Penicillamine長期效果在功能性狀況及影像進展惡化並不清楚。

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

1950年代DPenicillamine開始用於治療類風濕性關節炎,但其它修飾病程抗風濕藥物(DMARD)如Methotrexate增加使用後,其使用量已減少。Dpenicillamine在各種劑量範圍組似乎有效,包括關節疼痛及醫師總體評估及紅血球沈降速率上有統計上顯著差異。低劑量(小於500毫克/天) 與安慰劑組無顯著差異, 高劑量組Dpenicillamine 比安慰劑組退出使用高2倍。Dpenicillamine治療類風濕性關節炎疾病活性有臨床及統計上顯著差異。其效果與其它修飾病程抗風濕藥物(DMARD)相似,但使用Penicillamine時副作用較多。

Plain language summary

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.

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