Methotrexate for induction of remission in ulcerative colitis

  • Review
  • Intervention

Authors


Abstract

Background

Ulcerative colitis is a chronic inflammatory bowel disease. Corticosteroids and 5-aminosalicylates are the most commonly used therapies. However, many patients require immunosuppressive therapy when their disease becomes steroid-refractory or dependent. Methotrexate is a medication that is effective for treating a variety of inflammatory diseases, including Crohn's disease. This review was performed to determine the effectiveness of methotrexate at inducing remission in patients with ulcerative colitis.

Objectives

To review randomized trials examining the efficacy of methotrexate for remission induction in patients with ulcerative colitis.

Search methods

MEDLINE (PUBMED), EMBASE, The Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD group specialized trials register, review papers on ulcerative colitis, and references from identified papers were searched in an effort to identify all randomized trials studying methotrexate use in patients with ulcerative colitis. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only.

Selection criteria

Randomized controlled trials comparing methotrexate with placebo or an active comparator in patients with active ulcerative colitis were considered for inclusion.

Data collection and analysis

Data were extracted independently by each author, analyzed on an intention-to-treat basis, and treated dichotomously. Methotrexate was compared to placebo in one trial. The odds ratio and 95% confidence interval were calculated and P-values were derived using the chi-square test.

Main results

Only 1 trial fulfilled the inclusion criteria. This study randomized 30 patients to methotrexate 12.5 mg orally weekly and 37 patients to placebo for 9 months. During the study period, 14/30 patients (47%) assigned to methotrexate, and 18/37 patients (49%) assigned to placebo achieved remission and complete withdrawal from steroids (OR 0.92, 95% CI 0.35-2.42; P = 0.87). The mean time to remission was 4.1 months in the methotrexate group and 3.4 months in the placebo group.

Authors' conclusions

A single trial of methotrexate 12.5 mg orally weekly showed no benefit over placebo in remission induction in patients with active ulcerative colitis. There is no evidence on which to base recommendations for treating ulcerative colitis patients with methotrexate. However, the possibility of a type 2 error exists, and a higher dose of methotrexate may be effective. A new trial in which adequate numbers of patients are randomized to placebo or a higher dose of methotrexate should be considered.

摘要

背景

Methotrexate用於潰瘍性大腸炎誘導緩解

潰瘍性大腸炎是一種慢性的大腸發炎症狀,糖皮質類固醇和5ASA (5Aminosalicylic acid) 是最常被用來治療潰瘍性大腸炎的藥物,然而出現無法以類固醇進行治療或是對類固醇產生依賴的現象時,許多患者便需要進行免疫抑制治療。Methotrexate是一種能有效治療多種發炎性疾病的藥物,包括克隆氏症。本文獻回顧希望能夠確認methotrexate在誘導緩解潰瘍性大腸炎的功效。

目標

本文回顧評估以methotrexate緩解潰瘍性大腸炎患者效果的隨機性試驗。

搜尋策略

搜尋MEDLINE (PUBMED) 、EMBASE、 Cochrane Central Register of Controlled Trials、Cochrane IBD/FBD group specialized trials register、潰瘍性大腸炎的系統性文獻回顧及所找到文章的引用資料,以找出所有研究使用methotrexate於潰瘍性大腸炎病人的隨機對照試驗。搜尋重要腸胃道研討會的摘要,藉以找出僅發表摘要的研究。

選擇標準

以潰瘍性大腸炎患者為受試對象,比較methotrexate和安慰劑或一對照組 (active comparator) 治療效果的隨機對照試驗都會被考慮納入本文獻回顧中。

資料收集與分析

由每一位作者分別獨立的取出數據、以治療意向 (intentiontotreat) 為基礎進行分析,並進行二元性處理。在一試驗中是將methotrexate和安慰劑進行比較。計算勝算比 (odds ratio) 和95% 信賴區間 (confidence interval) ,利用卡方檢定來計算P值。

主要結論

只有一個試驗符合納入標準,這個試驗隨機選取30名患者,使其每星期口服12.5毫克的methotrexate,並隨機選取37名患者使用安慰劑,連續進行9個月,在研究期間,methotrexate組的30名病患中有14人 (47%) 、安慰劑組的37名病患中有18人 (49%) 症狀獲得緩解,並且可以完全停止使用類固醇 (OR值為0.92,95% CI 介於0.35至2.42間,P值為0.87) ,methotrexate組和安慰劑組的病患症狀獲得緩解的平均時間分別為4.1個月和3.4個月。

作者結論

一個單一試驗顯示,每週口服12.5毫克的methotrexate與安慰劑相比較之下,並methotrexate對潰瘍性大腸炎的患者無明顯緩解效果,目前尚無證據建議用來治療潰瘍性大腸炎患。然而,型2錯誤 (type 2 error) 是可能存在的,且高劑量的methotrexate可能可以對潰瘍性大腸炎產生功效。應該考慮利用一個新的試驗,將適當數量的患者隨機分配使其使用安慰劑或高劑量的methotrexate。

翻譯人

本摘要由劉家綺翻譯。

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

總結

尚無證據顯示低劑量的methotrexate能有效治療慢性活性潰瘍性大腸炎:低劑量的口服methotrexate (每星期使用12.5毫克) 並沒有出現可以緩解慢性活性克隆氏症的功效,應該要考慮進行一個試驗,納入較多數量的受試者使其使用高劑量的methotrexate,也應該進行一個新的試驗以確認methotrexate是不是可以對於非活性潰瘍性大腸炎的緩解產生維持效果。

Plain language summary

Methotrexate for treatment of chronic active ulcerative colitis

Low dose oral methotrexate (12.5 mg/week) was not shown to be effective for inducing remission in chronic active ulcerative colitis. A trial in which larger numbers of patients receive a higher dose of methotrexate should be considered. A new study could also determine if methotrexate is effective for maintaining remission in non-active ulcerative colitis.