SummaryBackgroundMethotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines.AimsTo review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD.MethodsWe conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed.ResultsFor Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid‐dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti‐tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild‐to‐moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low.ConclusionMethotrexate is effective at inducing and maintaining remission in steroid‐refractory Crohn's disease and can reduce anti‐TNF‐induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first‐line conventional option for the treatment of mild‐to‐moderate Crohn's disease.

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系统评价：甲氨蝶呤——一种人们对炎症性肠病了解甚少且未充分使用的药物


摘要背景 甲氨蝶呤是一种用于治疗炎症性肠病 (IBD) 的免疫抑制剂，已有 30 多年的历史，但与硫嘌呤相比，其使用率仍然较低。目的回顾甲氨蝶呤治疗成人 IBD 的疗效、安全性、最佳剂量和给药方案。方法我们进行了系统评价涉及从开始到 2023 年 8 月接受甲氨蝶呤治疗的 IBD 患者的研究。所有研究均通过 PubMed 从 MEDLINE 数据库中纳入。结果对于克罗恩病，我们纳入了 8 项随机对照试验 (RCT) 和 17 项观察性研究。肠外甲氨蝶呤可有效提高类固醇依赖患者的缓解率，每周 25 毫克持续 16 周，每周 15 毫克维持治疗。甲氨蝶呤可与抗肿瘤坏死因子（TNF）药物联合使用以降低免疫原性。比较硫嘌呤和甲氨蝶呤的数据仍然很少。对于溃疡性结肠炎 (UC)，我们纳入了 5 项随机对照试验和 10 项观察性研究；没有证据支持在（UC）中使用甲氨蝶呤。我们从 17 项研究中提取了安全性数据；轻度至中度不良反应很常见。肝纤维化或肝硬化的发生率较低。结论甲氨蝶呤可有效诱导和维持类固醇难治性克罗恩病的缓解，并且在联合治疗时可降低抗TNF诱导的免疫原性。有关耐受性和安全性的数据令人放心。这些发现挑战了关于甲氨蝶呤的先入为主的想法，并表明它是治疗轻至中度克罗恩病的有效一线常规选择。