Combination therapy for inflammatory bowel disease.

Keith S Sultan, Joshua C Berkowitz, Sundas Khan
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Abstract

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy (CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn's disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment naïve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC's conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

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炎症性肠病的综合疗法。
英夫利昔单抗和阿达木单抗等生物疗法已成为治疗炎症性肠病的主要手段。早期研究表明,英夫利昔单抗与硫唑嘌呤等免疫调节剂的联合疗法(CT)有助于优化生物药代动力学、降低免疫原性并改善疗效。具有里程碑意义的克罗恩病 SONIC 试验和溃疡性结肠炎 UC SUCCESS 试验表明,在诱导中度至重度疾病的治疗新患者获得临床缓解方面,英夫利西单抗和硫唑嘌呤联合疗法优于单独使用其中一种药物的单药疗法。然而,许多未解之谜仍悬而未决。CT 在非天真的患者中的作用以及 CT 的最佳持续时间仍是未知数。CT与其他生物制剂和/或其他免疫调节剂联合使用的效果也不明确,SONIC的结论是否可以推广到英夫利昔单抗和硫唑嘌呤以外的领域也不得而知。此外,CT 的风险也迫在眉睫,包括机会性感染和恶性肿瘤,尤其是淋巴瘤。本综述列出了与 CT 风险和益处相关的证据,以及需要进一步研究的领域。掌握了这些信息,医生就可以制定出最适合每位患者的治疗策略。
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