Sultan Keith S, Berkowitz Joshua C, Khan Sundas
Keith S Sultan, Department of Medicine, Division of Gastroenterology, Hofstra Northwell School of Medicine, Manhasset, NY 11030, United States.
World J Gastrointest Pharmacol Ther. 2017 May 6;8(2):103-113. doi: 10.4292/wjgpt.v8.i2.103.
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.
英夫利昔单抗和阿达木单抗等生物疗法已成为炎症性肠病治疗的主要手段。早期研究表明,英夫利昔单抗与硫唑嘌呤等免疫调节药物联合治疗(CT)可能有助于优化生物药代动力学、最小化免疫原性并改善治疗效果。克罗恩病的标志性SONIC试验以及溃疡性结肠炎的UC SUCCESS试验表明,在初治的中重度疾病患者中,英夫利昔单抗与硫唑嘌呤联合治疗在诱导临床缓解方面优于单独使用任何一种药物的单药治疗。然而,仍有许多未解决的问题。联合治疗在非初治患者中的作用以及联合治疗的最佳持续时间尚不清楚。使用替代生物制剂和/或替代免疫调节药物进行联合治疗的有效性尚不明晰,而且SONIC试验的结论是否能外推至英夫利昔单抗和硫唑嘌呤以外的药物也不清楚。联合治疗的风险也日益凸显,包括机会性感染和恶性肿瘤,尤其是淋巴瘤。本综述阐述了与联合治疗的风险和益处相关的证据以及需要进一步研究的领域。掌握这些信息后,从业者可以制定最适合每个患者的治疗策略。