Section of Gastroenterology, Division of Internal Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Children's Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Clin Gastroenterol Hepatol. 2019 Aug;17(9):1788-1798.e2. doi: 10.1016/j.cgh.2018.11.003. Epub 2018 Nov 15.
BACKGROUND & AIMS: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world.
We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness.
In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49-0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56-1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36-0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41-0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51-1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55-1.04).
In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.
尽管指南建议在抗肿瘤坏死因子（TNF）治疗开始时将免疫调节剂纳入克罗恩病（CD）或溃疡性结肠炎（UC）的治疗方案，但从真实世界的数据来看，这种治疗策略的附加疗效有限。
我们从 2001 年至 2016 年曼尼托巴省炎症性肠病（IBD）流行病学数据库中收集了开始接受 TNF 拮抗剂治疗的 CD（n=852）或 UC（n=303）患者的数据。在开始 TNF 拮抗剂治疗时，新开始使用或持续使用免疫调节剂的患者被认为接受了联合治疗。主要结局是 TNF 拮抗剂治疗期间或 TNF 拮抗剂停药后 90 天内的治疗无效（IBD 相关住院、肠道切除术、皮质类固醇使用或 TNF 拮抗剂更换）。我们使用 Cox 比例风险模型评估免疫调节剂联合使用与治疗无效之间的关系。
在 CD 患者中，联合治疗显著降低了治疗无效的可能性（治疗无效的调整后危险比[aHR]，0.62；95%可信区间[CI]，0.49-0.79）。然而，这种关联在 UC 患者中并不显著（aHR，0.82；95% CI，0.56-1.20）。在 CD 患者中，联合治疗还与首次 IBD 相关住院的时间延迟有关（aHR，0.53；95% CI，0.36-0.80）和 TNF 拮抗剂的更换（aHR，0.63；95% CI，0.41-0.97），但与 IBD 相关手术（aHR，0.76；95% CI，0.51-1.12）或新的或复发性皮质类固醇使用（aHR，0.75；95% CI，0.55-1.04）无关。
在对 IBD 真实世界患者数据库的分析中，我们发现，与单独使用 TNF 拮抗剂相比，联合使用免疫调节剂和 TNF 拮抗剂治疗 CD 患者的治疗无效可能性降低，但对 UC 患者无效。
