Anakinra for rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

In the past decade, a novel class of therapies directed against specific cytokines implicated in the disease process of rheumatoid arthritis (RA), called the 'Biologics' have greatly improved and expanded treatment for RA. Anakinra is an interleukin-1 receptor antagonist that is currently FDA-approved for moderate-severe RA that has been unresponsive to initial disease-modifying anti-rheumatic drugs (DMARD) therapy.

Objectives

To evaluate the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis.

Search methods

We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1950 to Week 4 2008) , EMBASE (1980 to Week 5 2008), CINAHL (1982 to November 2007) and reference lists of articles.

Selection criteria

Randomized controlled trials comparing anakinra alone or in combination with DMARDs or biologics to placebo or other DMARDs or biologics in patients >18 years old with rheumatoid arthritis.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.

Main results

Five trials involving 2876 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in number of participants achieving ACR20 (38% versus 23%) who were treated with anakinra 50 to 150 mg daily versus placebo after 24 weeks. This 15% increase in patients achieving ACR20 with anakinra versus placebo is felt to be a clinically meaningful, though modest, outcome. Other efficacy data - including ACR50 (18% versus 7%), ACR70 (7% versus 2%), HAQ, visual analog score (VAS), Larsen radiographic scores, and change in erythrocyte sedimentation rate (ESR) - all demonstrated significant improvement with anakinra 50 to 150 mg daily versus placebo as well. There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively. The incidence of serious infections was clinically higher, but not statistically different, in the anakinra (25/1366 patients, 1.8%) versus placebo group (3/534 patients, 0.6%).

Authors' conclusions

Anakinra is a relatively safe and modestly efficacious biologic therapy for rheumatoid arthritis. Although head to head comparison trials have not been carried out, the amount of improvement is notably less when compared to studies using other biologic therapies. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the long-term use of Anakinra has yet to be assessed.

摘要

背景

Anakinra治療類風濕性關節炎

近十年一類新的生物製劑直接對付影響類風濕性關節炎病程的細胞激素療法已經大大改善類風濕性關節炎的治療,其中界白素interleukin1(IL1)受體的拮抗劑Anakinra已經獲得美國食品和藥物管理局FDA通過治療以免疫調節劑治療無效之中重度類風濕性關節炎患者。

目標

評估Anakinra治療類成人風濕性關節炎之效果及安全性。

搜尋策略

搜尋包括Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008) EDLINE (1950 to Week 4 2008), EMBASE (1980 to Week 5 2008), CINAHL (1982 to November 2007)。同時搜尋所選文章之參考文獻。

選擇標準

隨機對照試驗於18歲以上類風濕性關節炎患者,比較單獨Anakinra或Anakinra加上免疫調節劑DMARDs或其它生物製劑比上安慰劑,或免疫調節劑DMARDs,或其它生物製劑。

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評估。亦聯絡作者獲得更多資訊。

主要結論

總共有5個研究包含2876例病患,其中2065位為治療組,781位為安慰劑組。每天使用anakinra 50到150 mg比上安慰劑,美國類風濕性疾病學學院(ACR 反應標準 20 (38% versus 23%)在24週達到顯著差異,相對於接受安慰劑,接受anakinra增加15% 美國類風濕性疾病學學院(ACR) 反應標準 0有臨床意義且為臨床中度效果。ACR50 (18% versus 7%), ACR70 (7% versus 2%), 健康評估問卷HAQ, 視覺類比量表visual analog score (VAS), Larsen影像分數, ESR改變皆有顯著差異。副作用包括退出、死亡、(全部及嚴重)不良反應、(全部及嚴重)感染大多與安慰劑無顯著差異。注射部位反應增加(71% versus 28%),嚴重感染在anakinra (25/1366 patients, 1.8%)稍多於安慰劑(3/534 patients, 0.6%),但無顯著差異。

作者結論

Anakinra治療類風濕性關節炎為臨床中度效果且相對安全。雖無與其他生物製劑一對一比較,其改善效果比其它生物製劑稍小。需進一步研究比較相對其它生物製劑之安全性及效果。長期anakinra使用之副作用尚未被評估。

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

Anakinra治療類風濕性關節炎: 這篇cochrane回顧展示了現在以anakrian治療類風濕性關節炎的效果,這篇回顧發現類風濕性關節炎患者使用6個月anakrian可改善類風濕性關節炎的症狀如疼痛、功能及僵硬。 什麼是類風濕性關節炎及anakrina 當你有類風濕性關節炎,通常你的免疫系統是對抗感染會攻擊關節的表面。這會使得你的關節腫脹、僵硬及疼痛。小的關節如手及足部通常最先被影響。目前沒有辦法治癒類風濕性關節炎。所以治療的目的在於減輕疼痛及僵硬,及改善活動能力。Anakinra是界白素interleukin1(IL1)受體的拮抗劑,可抑制發炎蛋白界白素IL1,用於治療以免疫調節劑治療無效之18歲以上中重度類風濕性關節炎患者。Anakinra可與其他治療類風濕性關節炎的藥物合併使用。 使用anakrina治療患者的最佳估計:每100位使用安慰劑患者23位在疼痛、功能及僵硬有改善,而使用Anakinra中每100位患者中38位有改善。每100位患者Anakinra治療6個月比安慰劑治療多15位有反應。

Plain language summary

Anakinra for Rheumatoid Arthritis

This summary of a Cochrane review presents what we know from research about the effect of Anakrina on rheumatoid arthritis (RA).

The review shows that in people with RA,

Taking Anakrina for 6 months may improve RA symptoms such as pain, function, and stiffness.

What are RA and Anakrina?

When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for RA at present, so the treatments aim to relieve pain and stiffness and improve your ability to move.  

Anakinra is an interleukin-1 receptor antagonist which is a drug that blocks the inflammatory protein interleukin-1. The drug is used to slow the progression of moderate to severe active RA in patients over age 18 who have not responded to one or more of  the disease-modifying anti-rheumatic drugs (DMARD).  Anakrina can be used with other RA drugs.

Best estimate of what happens to people with RA who take Anakrina:

23 out of 100 people experienced improvement of RA symptoms such as pain, function, and stiffness when taking a placebo

38 out of 100 people experienced improvement of RA symptoms such as pain, function, and stiffness when taking Anakrina

15 more people out of 100 experienced improvement of RA symptoms after taking Anakrina for 6 months compared with taking a placebo. 

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