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Infliximab for the treatment of rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA.

Objectives

To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis.

Search methods

Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed . The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below.

Selection criteria

All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible.

Data collection and analysis

Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks.

Main results

Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX) , 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control.

The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.94-3.33 for ACR 20, 3.57-4.76 for ACR 50 and 5.88 -12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks).

Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control.

Authors' conclusions

Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.

摘要

背景

Infliximab治療類風濕性關節炎

Infliximab是一種人鼠嵌合的抗腫瘤壞死因子α單株抗體,最近被通過用於治療頑固型類風濕性關節炎。

目標

評估Infliximab治療類風濕性關節炎之效果及安全性。

搜尋策略

搜尋包括Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE (1996直到2002年3月)。以類風濕性關節炎為關鍵字搜尋,而infliximb則以內文搜尋(因為最近尚未被索引)。搜尋不限制語言種類、發表時間及種類,搜尋的策略如下所示。

選擇標準

所有比較inflixima, 3, 5 or 10 mg/kg加上methotrexate(MTX)與只用MTX或無MTX只用安慰劑,至少6個月及至少打2次藥物之隨機臨床試驗。

資料收集與分析

兩位作者獨立進行資料摘錄,並對每篇試驗研究的品質以被證實過的評估工具進行評估。結果包括了美國風濕病學學會類風濕性關節炎臨床試驗疾病活性核心指標及X光結果,也包括退出及毒性資料。所有試驗結果被總和,二分法類別資料使用相對風險(RR)來表示,連續性資料使用加權平均差異分析。

主要結論

2個研究包含529例病患符合收入條件。符合美國風濕病學學會類風濕性關節炎診斷標準的病患被隨機分配接受Infliximab 1mg/kg (加與不加MTX), 3mg/kg(加與不加 MTX) 0mg/kg of infliximab (加與不加MTX 或安慰劑注射加MTX。每4或8週注射。6個月後AC 0, ACR 50及ACR 70反應率都比控制組高。在接受專科治療的頑固型類風濕性關節炎患者達到ACR 20, ACR 50 or ACR 70的需要被治療的病人數目NNT依據劑量的不同分別為 2.94 – 3.33, 3.57 – 4.76, 5.88 – 12.5 (劑量範圍 mg/kg 或10mg/kg 每4或8週注射)。整體退出及因無效退出,在Infliximab各劑量組比控制組少。因副作用及其他因素退出,Infliximab與控制組並無統計學上顯著差異。

作者結論

Infliximab 治療6及12個月明顯減少疾病活性且有相當安全性。在12個月時infliximab比控制組整體X光分數進步,較少病患X光繼續惡化,較多病患有X光的改善。但只含2篇大型研究,且結果被最大的研究所主導,其有效性及安全性為短期6到12個月資料,如果要發現少見的事件則需更久及更大型研究評估。

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

Infliximab合併methotrexate是一種有效的治療類風濕關節炎方法。Infliximab是一種較新的疾病調節抗風濕藥物,可抑制腫瘤壞死因子α。短期(6至12個月)的研究表明Infliximab的耐受性良好,且結合methotrexate可降低類風濕關節炎疾病活性。Infliximab 3mg/kg或10mg/kg,合併methotrexate,每4或8週使用一次並連續 6或12個月,顯著改善疾病的活性(以疼痛、關節腫脹、ACR反應率作為衡量標準)。與那些只服用methotrexate相比,疼痛和生理功能也有改善。在12個月後,Infliximab顯著降低其關節惡化在X光下的表現。

Plain language summary

Infliximab for rheumatoid arthritis

Infliximab in combination with methotrexate is an effective treatment for rheumatoid arthritis( RA).

Infliximab is a relatively new disease modifying anti-rheumatic drug that inhibits tumour necrosis factor alpha. Short term (six to twelve month) studies suggest infliximab is well tolerated, and in combination with methotrexate, decreases disease activity in RA. Infliximab 3mg/kg or 10mg/kg, in combination with methotrexate, taken every 4 or 8 weeks for either 6 or 12 months, significantly improved disease activity as measured by tender and swollen joints and ACR response rates. Pain and physical function also improved compared to those taking methotrexate alone. Infliximab significantly reduced radiographic progression at 12 months.

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