Introduction: The management of patients with ulcerative colitis (UC) has evolved over the past few decades. While aminosalicylates remain the mainstay of induction and maintenance therapy in patients with mild-to-moderate UC, the advent of biologic agents and novel oral small molecules has substantively changed the treatment landscape for patients with moderate-to-severe disease and confounded the role of traditional immunomodulators (IMMs) such as thiopurines and methotrexate in the UC management algorithm.

Areas covered: We summarize the mechanism of action of thiopurines and methotrexate, identify clinical parameters for their use, and appraise the evidence supporting the efficacy and safety of IMMs in UC as both monotherapy and in combination with other therapies, emphasizing on prospective, controlled data.

Expert opinion: With the advent of several classes of highly effective treatments for UC, emergence of data demonstrating no benefit of IMMs over placebo, and concerns about the relative safety profile of long-term IMM exposure, we propose that the role of thiopurines or methotrexate be restricted to patients with milder disease failing to maintain corticosteroid-free remission on aminosalicylates alone or in combination therapy with tumor necrosis factor antagonists in patients with moderate-to-severe UC.

简介：在过去的几十年中，溃疡性结肠炎（UC）的患者管理有所发展。虽然氨基水杨酸酯仍然是轻度至中度UC患者诱导和维持治疗的主要手段，但生物制剂和新型口服小分子药物的出现已从根本上改变了中重度疾病患者的治疗前景，并混淆了UC管理算法中使用了传统的免疫调节剂（IMM），例如硫嘌呤和氨甲蝶呤。

涵盖的领域：我们总结了硫嘌呤和甲氨蝶呤的作用机理，确定了其使用的临床参数，并评估了支持IMM在UC中作为单一疗法或与其他疗法联合使用的有效性和安全性的证据，重点在于前瞻性，可控制的数据。

专家意见：随着几类针对UC的高效治疗方法的出现，数据的出现，证明IMM与安慰剂相比无益处，并且担心长期IMM暴露的相对安全性，我们建议使用硫嘌呤或甲氨蝶呤的作用仅限于中度至重度UC患者单独使用氨基水杨酸酯或与肿瘤坏死因子拮抗剂联合治疗无法维持无糖皮质激素缓解的轻度疾病患者。