Background & Aims

This American Gastroenterological Association (AGA) living guideline is intended to support practitioners in the pharmacological management of moderate-to-severe ulcerative colitis (UC).

Methods

A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations on the pharmacological management of moderate-to-severe UC.

Results

The AGA guideline panel made 14 recommendations. In adult outpatients with moderate-to-severe UC, the AGA recommends the use of infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab, and suggests the use of adalimumab, filgotinib, and mirikizumab over no treatment. In patients who are naïve to advanced therapies, the AGA suggests using a higher-efficacy medication (eg, infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, and guselkumab) or an intermediate-efficacy medication (eg, golimumab, ustekinumab, tofacitinib, filgotinib, and mirikizumab) rather than a lower-efficacy medication (eg, adalimumab). In patients who have previously been exposed to 1 or more advanced therapies, particularly tumor necrosis factor (TNF)-α antagonists, the AGA suggests using a higher-efficacy medication (eg, tofacitinib, upadacitinib, and ustekinumab) or an intermediate-efficacy medication (eg, filgotinib, mirikizumab, risankizumab, and guselkumab) rather than a lower-efficacy medication (eg, adalimumab, vedolizumab, ozanimod, and etrasimod). In adult outpatients with moderate-to-severe UC, the AGA suggests against using thiopurine monotherapy for induction of remission, but suggests using thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission. The AGA suggests against using methotrexate monotherapy, for induction or maintenance of remission. In adult outpatients with moderate-to-severe UC, the AGA suggests the use of infliximab, adalimumab, and golimumab in combination with an immunomodulator over corresponding monotherapy. However, the AGA makes no recommendation in favor of, or against, the use of non-TNF antagonist biologics in combination with an immunomodulator over non-TNF biologic alone. In patients with UC who are in corticosteroid-free clinical remission for at least 6 months on combination therapy of TNF antagonists and an immunomodulator, the AGA suggests against withdrawal of TNF antagonists, but makes no recommendation in favor of, or against, withdrawing immunomodulators. In adult outpatients with moderate-to-severe UC, who have failed 5-aminosalicylates, and have escalated to therapy with immunomodulators or advanced therapies, the AGA suggests stopping 5-aminosalicylates. Finally, in adult outpatients with moderate-severe UC, the AGA suggests early use of advanced therapies and/or immunomodulator therapy, rather than gradual step-up after failure of 5-aminosalicylates. The panel also proposed key implementation considerations for optimal use of these medications and identified several knowledge gaps and areas for future research.

Conclusions

This guideline provides a comprehensive, patient-centered approach to the pharmacological management of patients with moderate-to-severe UC.

中文翻译：

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AGA 中度至重度溃疡性结肠炎药物治疗的 AGA Living Clinical Practice Guide

 背景和目标

该美国胃肠病学协会 （AGA） 实时指南旨在支持从业者对中度至重度溃疡性结肠炎 （UC） 进行药物治疗。

 方法

由内容专家和指南方法论者组成的多学科小组使用建议分级评估、开发和评价 （GRADE） 框架来确定临床问题的优先级，确定以患者为中心的结局，进行证据综合，并就中度至重度 UC 的药物管理提出建议。

 结果

AGA 指南小组提出了 14 条建议。对于中度至重度 UC 成人门诊患者，AGA 建议使用英夫利昔单抗、戈利木单抗、维得利珠单抗、托法替尼、乌帕替尼、乌司奴单抗、奥扎莫德、依曲莫德、瑞沙珠单抗和古塞奇尤单抗，并建议使用阿达木单抗、filgotinib 和 mirikizumab 而不是不治疗。对于未接受过先进治疗的患者，AGA 建议使用更有效的药物（例如，英夫利昔单抗、维多珠单抗、奥扎莫德、依曲莫德、乌帕替尼、瑞沙珠单抗和古塞奇尤单抗）或中等疗效药物（例如，戈利木单抗、乌特克单抗、托法替尼、filgotinib 和 mirikizumab），而不是低效药物（例如，阿达木单抗）。对于既往接受过 1 种或多种先进治疗的患者，特别是肿瘤坏死因子 （TNF） α拮抗剂的患者，AGA 建议使用更有效的药物（例如，托法替尼、upadacitinib 和乌司奴单抗）或中等疗效药物（例如，filgotinib、mirikizumab、risankizumab 和 guselkumab），而不是低效药物（例如，阿达木单抗、维多珠单抗、奥扎莫德和依曲莫德）。在中度至重度 UC 成人门诊患者中，AGA 建议不要使用硫嘌呤单药治疗来诱导缓解，但建议使用硫嘌呤单药治疗而不是不治疗来维持（通常是皮质类固醇诱导的）缓解。AGA 建议不要使用甲氨蝶呤单药治疗来诱导或维持缓解。在中度至重度 UC 成人门诊患者中，AGA 建议将英夫利昔单抗、阿达木单抗和戈利木单抗联合免疫调节剂使用，而不是相应的单药治疗。 然而，AGA 没有建议支持或反对使用非 TNF 拮抗剂生物制剂与免疫调节剂联合使用，而不是单独使用非 TNF 生物制剂。对于接受 TNF 拮抗剂和免疫调节剂联合治疗至少 6 个月的无皮质类固醇临床缓解的 UC 患者，AGA 建议不要停用 TNF 拮抗剂，但没有提出支持或反对停用免疫调节剂的建议。对于中度至重度 UC 成人门诊患者，如果 5-氨基水杨酸盐治疗失败，并已升级为免疫调节剂或高级疗法，AGA 建议停用 5-氨基水杨酸盐。最后，在中重度 UC 成人门诊患者中，AGA 建议早期使用先进疗法和/或免疫调节剂疗法，而不是在 5-氨基水杨酸盐治疗失败后逐渐增加。该小组还提出了优化使用这些药物的关键实施考虑因素，并确定了几个知识差距和未来研究的领域。

 结论

该指南为中度至重度 UC 患者的药物治疗提供了一种全面的、以患者为中心的方法。