Ahmed Waseem, Galati Jonathan, Kumar Anand, Christos Paul J, Longman Randy, Lukin Dana J, Scherl Ellen, Battat Robert
Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, New York.
Department of Medicine, New York University School of Medicine, New York, New York.
Clin Gastroenterol Hepatol. 2022 Mar;20(3):e361-e379. doi: 10.1016/j.cgh.2021.03.034. Epub 2021 Mar 31.
We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD).
Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy.
We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn's disease; median duration of treatment 24 weeks (IQR-IQR 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR-IQR 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I = 0%), endoscopic remission (P = .44, I = 0%), and malignancy (P = .87, I = 0%). However, significant heterogeneity existed for other outcomes.
Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.
我们进行了一项系统评价和荟萃分析，以总结关于双重生物治疗联合或与托法替布联用治疗难治性炎症性肠病（IBD）患者的安全性和有效性的新数据。
通过系统检索截至2020年11月9日的多个电子数据库，我们确定了队列研究或病例系列（>10例患者），报告了IBD患者同时使用生物制剂联合或与托法替布联用的安全性和有效性。使用汇总数据综合分析不良事件、临床缓解和内镜缓解率，并确定与双重治疗成功相关的因素。
我们确定了30项研究，报告了279例患者（76%为克罗恩病；中位治疗持续时间24周（IQR - IQR 13 - 32））的288项双重生物制剂或小分子治疗试验。双重治疗的主要适应证包括药物难治性IBD（81%）和并发肠外表现或风湿性疾病（12%）。双重治疗最常见的组合包括肿瘤坏死因子-α拮抗剂和抗整合素（48%）、乌司奴单抗和抗整合素（19%）；61%的患者之前至少对联合使用的两种治疗中的一种治疗失败。在中位随访32周（IQR - IQR 24 - 52）期间，不良事件和严重不良事件的汇总发生率分别为31%（95%CI，13% - 54%）和6.5%（95%CI，2.1% - 13.1%）；临床缓解和内镜缓解的汇总发生率分别为59%（95%CI，42% - 74%）和34%（95%CI，23% - 46%）。12%（95%CI，4% - 24%）的患者需要手术。因肠外表现接受双重治疗的患者成功率更高。内镜反应（P = 0.88，I² = 0%）、内镜缓解（P = 0.44，I² = 0%）和恶性肿瘤（P = 0.87，I² = 0%）的异质性不显著。然而，其他结局存在显著异质性。
双重生物制剂或小分子治疗可能是专科中心高度选择的难治性IBD患者的一种选择。在更广泛应用之前，需要更高质量的联合治疗以及数据质量的显著改善。
