Division of Clinical Immunology and Rheumatology, Department of Medicine, Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA.
Inflamm Bowel Dis. 2021 Aug 19;27(9):1394-1408. doi: 10.1093/ibd/izaa289.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program.
Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157).
Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73-4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06-1.93); HZ, 1.77 (1.34-2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43-0.90); NMSC, 1.69 (1.35-2.10); major adverse cardiovascular events (MACE), 0.51 (0.31-0.79); pulmonary embolism (PE), 0.54 (0.30-0.89); deep vein thrombosis (DVT), 1.41 (1.00-1.93); and gastrointestinal perforations, 0.31 (0.16-0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27-2.36]), OIs (excluding HZ; 0.16 [0.04-0.42]), NMSC (0.78 [0.47-1.22]), PE (0.16 [0.04-0.41]), and DVT (0.04 [0.00-0.23]), and a higher rate for HZ (3.57 [2.84-4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar.
When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher.
CLINICALTRIALS.GOV: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
托法替尼是一种用于治疗溃疡性结肠炎（UC）的口服小分子 Janus 激酶抑制剂。我们旨在通过真实世界人群队列估计 UC 患者的安全性事件的总体发生率，以便与托法替尼 UC 临床试验计划进行比较。
对 IBM MarketScan®索赔数据库中基于人群的 UC 患者队列（2010 年 10 月至 2015 年 9 月）应用类似于临床试验的标准，以确定接受肿瘤坏死因子抑制剂（TNFi；n = 6366）治疗的类似于 UC 临床试验的队列，与托法替尼 UC 临床试验队列（n = 1157）进行比较。
UC 类似临床试验队列的发生率（每 100 患者年发生的事件数；[95%置信区间]）如下：严重感染，3.33（2.73-4.02）；机会性感染（不包括带状疱疹[HZ]），1.45（1.06-1.93）；HZ，1.77（1.34-2.29）；恶性肿瘤（不包括非黑色素瘤皮肤癌[NMSC]），0.63（0.43-0.90）；NMSC，1.69（1.35-2.10）；主要不良心血管事件（MACE），0.51（0.31-0.79）；肺栓塞（PE），0.54（0.30-0.89）；深静脉血栓形成（DVT），1.41（1.00-1.93）；和胃肠道穿孔，0.31（0.16-0.54）。与 UC 类似临床试验队列相比，接受托法替尼治疗的患者严重感染（1.75 [1.27-2.36]）、不包括 HZ 的机会性感染（0.16 [0.04-0.42]）、NMSC（0.78 [0.47-1.22]）、PE（0.16 [0.04-0.41]）和 DVT（0.04 [0.00-0.23]）的发生率较低，HZ 发生率较高（3.57 [2.84-4.43]）；恶性肿瘤（不包括 NMSC）、MACE 和胃肠道穿孔的发生率相似。
在承认将索赔数据与对照临床试验数据进行比较的局限性时，UC 类似临床试验队列中接受 TNFi 治疗的患者中 HZ 的发生率低于托法替尼 UC 临床试验队列；严重感染、机会性感染、NMSC、PE 和 DVT 的发生率较高。
临床试验.gov：NCT00787202、NCT01465763、NCT01458951、NCT01458574、NCT01470612。
