Golimumab for rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

Golimumab is a humanized inhibitor of Tumor necrosis factor-alpha, recently approved by the Food and Drug Administration (FDA) for the treatment of Rheumatoid arthritis (RA). 

Objectives

The objective of this systematic review was to compare the efficacy and safety of golimumab (alone or in combination with DMARDs or biologics) to placebo (alone or in combination with DMARDs or biologics) in randomized or quasi-randomized clinical trials in adults with RA.

Search methods

An expert librarian searched six databases for any clinical trials of golimumab in RA, including the Cochrane Central Register of Controlled Trials (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials databases.

Selection criteria

Studies were included if they used golimumab in adults with RA, were randomized or quasi-randomized and provided clinical outcomes.

Data collection and analysis

Two review authors (JS, SN) independently reviewed all titles and abstracts, selected appropriate studies for full review and reviewed the full-text articles for the final selection of included studies. For each study, they independently abstracted study characteristics, safety and efficacy data and performed risk of bias assessment. Disagreements were resolved by consensus. For continuous measures, we calculated mean differences or standardized mean differences and for categorical measures, relative risks. 95% confidence intervals were calculated.

Main results

Four RCTs with 1,231 patients treated with golimumab and 483 patients treated with placebo were included. Of these, 436 were treated with the FDA-approved dose of golimumab 50 mg every four weeks. Compared to patients treated with placebo+methotrexate, patients treated with the FDA-approved dose of golimumab+methotrexate were 2.6 times more likely to reach ACR50 (95% confidence interval (CI) 1.3 to 4.9; P=0.005 and NNT= 5, 95% confidence interval 2 to 20), no more likely to have any adverse event (relative risk 1.1, 95% Cl 0.9 to 1.2; P=0.44), and 0.5 times as likely to have overall withdrawals (95% Cl 0.3 to 0.8; P=0.005). Golimumab-treated patients were significantly more likely to achieve remission, low disease activity and improvement in functional ability compared to placebo (all statistically significant). No significant differences were noted between golimumab and placebo regarding serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events and inefficacy and deaths. No radiographic data were reported.

Authors' conclusions

With an overall high grade of evidence, at the FDA-approved dose, golimumab is significantly more efficacious than placebo in treatment of patients with active RA , when used in combination with methotrexate. The short-term safety profile, based on short-term RCTs, is reasonable with no differences in total adverse events, serious infections, cancer, tuberculosis or deaths. Long-term surveillance studies are needed for safety assessment.

摘要

Golimumab於類風濕性關節炎

研究背景

Golimumab是一種人源化的腫瘤壞死因子α抑制劑,最近被美國食品藥物管理局核准用在類風濕性關節炎的治療

研究目的

這篇系統性回顧的目第是比較golimumab(單獨或合併使用疾病修飾抗風濕藥物(DMARDs)或生物製劑),和安慰劑(單獨或合併使用疾病修飾抗風濕藥物或生物製劑)在成人類風濕關節炎的療效和安全性的隨機或半隨機臨床試驗。

检索策略

由一位專家管理員在6個資料庫裡搜尋有關golimumab使用在類風濕關節炎的任何臨床試驗,這些資料庫包括Cochrane Central Register of Controlled Trials (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials databases。

标准/纳入排除标准

研究文章包含使用golimumab類風濕關節炎的成人,且為隨機或半隨機試驗,並提供臨床療效。

数据收集与分析

兩個審查作者(JS, SN)獨立審查所有標題和摘要,選擇適當的研究做全面性的回顧,並審查了全文文章以最後決定進入此 分析研究。對於每一個研究中,他們獨立分離出研究的特點,安全性和有效性的數據,並進行風險評估的偏見。以共識來解決分歧。對於連續性的測量,我們計算平均差或標準化平均差和明確的措施,相對風險。且對95%信賴區間進行了計算。

主要结果

在4個隨機事件中,包含了以golimumab治療的1,231個病人、安慰劑治療的483個病人。這些病人中有436個病人被處方以FDA核准的golimumab 50mg每四週一次。相較於安慰劑+methotrexate,病患以FDA核准的golimumab劑量加上methotrexate有2.6倍更能達到ACR50(95% confidence interval (CI) 1.3 to 4.9; P = 0.005 and NNT = 5,95% confidence interval 2 to 20),沒有增加任何可能的副作用(relative risk 1.1, 95% Cl 0.9 to 1.2; P = 0.44), 和整體0.5倍退出研究(95% Cl 0.3 to 0.8; P = 0.005)。與安慰劑相比,以Golimumab治療的患者顯著更能達到緩解,低疾病活動和改善身體功能(皆有統計學意義)。 golimumab和安慰劑之間在嚴重不良反應、感染、嚴重感染、肺部感染、結核病、癌症,因不良反應、無效和死亡而退出研究方面,皆無顯著統計差異。沒有影像學資料的報告。

作者结论

隨著整體有力的證據指出,在FDA批准的劑量下,golimumab加上methotrexate明顯比安慰劑加methotrexate更有效的治療活動期類風濕關節炎患者。根據短期隨機對照試驗,在短期的安全性上,是合理的,對於總不良反應、嚴重感染、腫瘤、肺結核或死亡是沒有差異的。對於安全性的評估,長期監測研究還是需要的。

Plain language summary

Golimumab for rheumatoid arthritis

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

The review shows that in people with rheumatoid arthritis;

- Golimumab improves the number of tender or swollen joints and other outcomes such as pain and disability (ACR 50).

- Golimumab increases the number of people in remission.

- Slightly more people who take Golimumab will have minor side effects (such as a minor infection), but this may be the result of chance. There is no difference in the number of people who will have a serious adverse event, compared to people who took a placebo. 

We do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include a serious infection or upper respiratory infection. Rare complications may include certain types of cancer.

What is rheumatoid arthritis (RA) and what are is golimumab?

When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints making them inflamed. This inflammation causes your joints to be hot, swollen, stiff, and painful. The small joints of your hands and feet are usually affected first.  If the inflammation goes on without treatment, it can lead to damaged joints.  Once the joint is damaged it cannot be repaired, so treating rheumatoid arthritis early is important.

Golimumab is an anti-tumor necrosis factor (TNF)-alpha biologic drug.  Biologics are a group of medications that suppress the immune system and reduce the inflammation in the joints.  Even though suppressing the immune system can make it slightly harder to fight off infections, it also helps to stabilize an overactive immune system. By reducing the inflammation, the aim is to help prevent damage to the joints.  Golimumab is an injection given once a month.

Best estimate of what happens to people with rheumatoid arthritis who take golimumab:

ACR 50 (number of tender or swollen joints and other outcomes such as pain and disability)

- 23 more people out of 100 experienced improvement in the symptoms of their rheumatoid arthritis after 14-24 weeks with golimumab (23% absolute improvement).

- 38 people out of 100 who took golimumab experienced improvement.

- 15 people out of 100 who took a placebo experienced improvement.

Disease Remission

- 18 more people out of 100 were considered to be in remission after 14-24 weeks with golimumab (18% absolute improvement).

- 22 people out of 100 were considered to be in remission with golimumab.

- 4 people out of 100 were considered to be in remission with placebo.

 People who dropped out of the studies due to any reason

- 5 fewer people out of 100 who took golimumab dropped out of the studies for any reason.  (2% absolute difference)

- 5 people out of 100 who took golimumab dropped out of the studies for any reason.

- 10 people out of 100 who used a placebo dropped out of the studies for any reason.

概要

Golimumab於類風濕性關節炎:從Cochrane回顧的摘要呈現了我們所知道的關於生物製劑在類風溼關節炎的療效。這個回顧指出,golimumab改善了類風濕關節炎病患疼痛和腫脹的關節數目以及其他的預後,如疼痛和殘疾(ACR50)。golimumab使疾病緩解的人數增加。使用golimumab少許增加輕微的副作用(如輕微感染),但這可能是偶然的結果。與服用安慰劑的人相較,產生嚴重不良事件的病人數沒有區別。我們沒有確切的副作用和併發症的資訊,尤其是如此罕見但嚴重的副作用。可能的副作用可能包括嚴重的感染或上呼吸道感染。罕見的併發症可能包括某些類型的癌症。何謂類風濕性關節炎?何謂golimumab?當你有類風濕關節炎,你的免疫系統,正常抵擋感染,卻攻擊你的關節使它們發炎。這種發炎使你的關節熱、腫脹、僵硬、疼痛。你的手和腳的小關節通常是首當其衝。如果不經治療讓發炎繼續,它會導致關節損壞。一旦關節被破壞將無法修復,所以早期治療類風濕關節炎是重要的。golimumab是一種抑制腫瘤壞死因子α的生物製劑。生物製劑是一組藥物,可以抑制免疫系統,減少關節發炎。儘管抑制免疫系統會稍微難以抵禦感染,但它也有助於穩定過於活躍的免疫系統。透過減少發炎,目的是避免關節壞。golimumab一個月注射一次。最佳估計是有類風濕關節炎的人使用golimumab後:其ACR50(疼痛和腫脹的關節數目和其他結果,如疼痛和殘疾)每100人有超過23人在第14–24週後得到類風濕關節炎症狀改善(23%絕對改善);100人裡有38人症狀有改善,而每100人中只有15人使用安慰劑得到進步。疾病緩解方面(remission)100人有超過18人在14–24週後達到疾病緩解(18%絕對改善)。每100人有22人使用golimumab達到緩解,而使用安慰劑每100人只有4人達到緩解。在任何原因退出研究的人之中,有小於5%的人使用golimumab因任何原因退出(2%絕對差)。100人有5人使用golimumab因任何原因退出研究,而使用安慰劑100人有10人因任何原因退出研究。

翻译注解

Ancillary