Methotrexate for ankylosing spondylitis

 

Abstract

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterised by sacroiliitis and spondylitis. Generally, treatment is limited to the alleviation of symptoms using non-steroidal anti-inflammatory drugs (NSAIDs). Recently, disease-modifying antirheumatic drugs (DMARDs) have been used for patients for whom NSAIDs do not work. Methotrexate (MTX), a widely used DMARD, is effective for rheumatoid arthritis (RA), and so might work for AS too.

Objectives

To evaluate the efficacy and toxicity of MTX for treating AS.

Search methods

We conducted searches in any language in: CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 20, 2005); EMBASE (1980 to November 20, 2005); CINAHL (1982 to November 20, 2005), and the reference sections of retrieved articles.

Selection criteria

Randomised and quasi-randomised trials examining the efficacy of MTX versus placebo, other medication, or no medication, for AS.

Data collection and analysis

Two reviewers independently assessed unblinded trial reports for inclusion, assessed methodological quality and entered trial data into RevMan 4.2 using the double-entry facility. Disagreements were resolved by a third reviewer. In the absence of significant heterogeneity, results for continuous data were combined using weighted mean difference or standardised mean difference. Relative risk was used for dichotomous data.

Main results

Three trials, involving 116 patients, were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. Only the response rate in one trial showed a statistically significant benefit of 36% in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX is questionable. No serious side effects were reported in these trials.

Authors' conclusions

There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality randomised controlled trials of longer durations and with larger sample sizes are needed to clarify the effect(s) of MTX on AS.

 

Plain language summary

Methotrexate for ankylosing spondylitis

This summary of a Cochrane review presents what we know from research about the effect of methotrexate for ankylosing spondylitis. The review shows that:

There is silver level evidence (www.cochranemsk.org) that for people with ankylosing spondylitis, methotrexate may not improve overall disease activity, physical function, overall pain, pain, tenderness and swelling in the ligaments of the joints, movement of the spine, stiffness or overall well being. It may not cause serious side effects. But there is not enough evidence to be certain of the benefits and harms of methotrexate for ankylosing spondylitis and more research is needed.

What is ankylosing spondylitis and what drugs are used to treat it?
Ankylosing spondylitis (AS) is a type of arthritis, usually in the joints and ligaments of the spine. It may also affect the shoulders, hips, or other joints. Pain and stiffness occurs and limits movement in the back and in other joints that are affected.

Non steroidal anti-inflammatory drugs (NSAIDs) are usually used to stop the pain and stiffness. When people do not do well with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, are sometimes prescribed. It is not known whether methotrexate controls pain and stiffness in AS, slows the progress of AS, or can stop joint damage.

What are the results of this review?
Benefits of methotrexate
In people with ankylosing spondylitis, at 6 to 12 months, methotrexate

may not improve overall disease activity, physical function, overall pain, pain, tenderness or swelling in the ligaments of the joints, movement of the spine, stiffness and overall well being. But there is not enough evidence to be certain.

Damage to the spine as seen on x-ray was not measured and therefore it is not known whether methotrexate slows damage.

Harms of methotrexate
In people with ankylosing spondylitis, at 6 to 12 months, methotrexate may not cause serious side effects. But there is not enough evidence to be certain. Side effects may include nausea, stomach pain, vomiting, mild diarrhea, mild headaches, mouth sores, changes in liver function, hair loss or mild infections.

 

摘要

背景

胺基甲基葉酸治療僵直性脊椎炎

僵直性脊椎炎(AS)是一種原因不明的慢性發炎疾病，其特徵是?髂關節炎和脊椎炎，一般來說，治療僅限於使用非類固醇抗炎藥物(NSAIDs)緩解症狀。最近，疾病調節抗風濕藥物(DMARDs)已被用於治療非類固醇抗炎藥物沒有效的病人，胺基甲基葉酸(MTX) 是一種被廣泛使用於治療類風濕關節炎(RA)的疾病調節抗風濕藥，可能對治療僵直性脊椎炎有效。

目標

評估胺基甲基葉酸治療僵直性脊椎炎的療效和毒性。

搜尋策略

我們搜尋以任何語言在 CENTRAL (The Cochrane Library Issue 4, 2005) MEDLINE(1966 to November 20, 2005) EMBASE(1980 to November 20, 2005) CINAHL(1982 to November 20, 2005)發表的研究，以及參考部分引文。

選擇標準

以隨機和半隨機對照試驗比較胺基甲基葉酸與安慰劑，其他藥物和不使用藥物的療效 。

資料收集與分析

兩個審查者獨立評估非盲測試驗報告的納入標準和評估方法的品質，將試驗數據輸入到RevMan 4.2使用複式輸入設備，分歧的結果由第三個審查者重複評估。由於無重要的異質性，連續數據的結果合併使用加權平均差或標準化平均差，相對危險度用於二分法數據。

主要結論

三個試驗共包括116例患者：一個12個月的試驗比較naproxen 加胺基甲基葉酸與單獨使用naproxen，兩個24週的試驗比較不同劑量胺基甲基葉酸與安慰劑， 基本結果無統計上的顯著差異，包含身體機能，疼痛，脊椎活動性，周邊關節/肌腱疼痛，腫脹和壓痛，脊椎X光片的變化，病患和醫生的整體評估。在一個胺基甲基葉酸組對照安慰劑組的試驗中，只有回應率表現出36 ％顯著效益(RR 3.18, 95% CI 1.03 to 9.79)，回應率是一個綜合指數，其中包括評估早晨僵硬，身體健康，貝氏僵直性脊椎炎疾病活動指數(BASDAI) ，貝氏僵直性脊椎炎功能指數(BASFI)，脊椎關節病變健康評估問卷(HAQS)和醫生與患者的整體評估，然而最後結果進行比較時，沒有單一結果顯示胺基甲基葉酸組和安慰劑組有統計上的顯著差異，因此胺基甲基葉酸的好處值得懷疑，這些試驗沒有嚴重的副作用報告。

作者結論

沒有足夠的證據支持胺基甲基葉酸治療僵直性脊椎炎有任何好處，需要研究時間更長，樣本更大的高質量隨機對照試驗來澄清胺基甲基葉酸對僵直性脊椎炎的效果。

翻譯人

本摘要由林口長庚醫院賴伯亮翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

這個考科藍文獻回顧摘要提出了我們從研究所知胺基甲基葉酸治療強僵直性脊椎炎的影響，這個文獻回顧顯示：有銀級證據(www.cochranemsk.org)證實，胺基甲基葉酸對於僵直性脊椎炎者，可能不會提高整體疾病活動，身體功能，整體疼痛，關節韌帶的疼痛，壓痛和腫脹，脊椎活動，它可能不會引起嚴重的副作用，但是沒有足夠的證據來確定胺基甲基葉酸治療僵直性脊椎炎的利益和損害，更多的研究是必要的。什麼是僵直性脊椎炎，用什麼藥物來治療呢？僵直性脊椎炎(AS)是一種關節炎，通常發生在脊椎的關節和韌帶。它也可能影響到肩膀，臀部，或其他關節，產生疼痛和僵硬，限制背部和其他關節的活動。非類固醇抗炎藥(NSAIDs)通常用來阻止疼痛和僵硬，當非類固醇抗炎藥效果不張時，疾病調節抗風濕藥物(DMARDs)如胺基甲基葉酸有時會被考慮使用。目前還不清楚胺基甲基葉酸的作用，是否能控制僵直性脊椎炎的疼痛和僵硬，還是能減緩疾病的進展，或是可以停止關節的傷害。這個文獻回顧的結論為何？胺基甲基葉酸治療僵直性脊椎炎6至12個月的好處：胺基甲基葉酸可能不會改善整體疾病活動，身體功能，整體疼痛，韌帶關節的疼痛，觸痛或腫脹，脊柱活動，僵硬和整體幸福感，但是沒有足夠的證據來確定。 X 射線可見的脊椎損害沒有計量， 因此目前尚不清楚是否胺基甲基葉酸可減緩脊椎的損害。胺基甲基葉酸治療僵直性脊椎炎6至12個月的傷害：胺基甲基葉酸可能不會引起嚴重的副作用，但是沒有足夠的證據來確定，副作用可能包括噁心，胃痛，嘔吐，輕度腹瀉，輕度頭痛，口腔潰瘍，肝功能改變，脫髮或輕微的感染。