Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
United European Gastroenterol J. 2024 Jul;12(6):793-801. doi: 10.1002/ueg2.12584. Epub 2024 May 22.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report an integrated summary of tofacitinib safety from the completed global UC clinical program (9.2 years maximum tofacitinib exposure).
This analysis included patients receiving tofacitinib 5 or 10 mg twice daily (b.i.d.) from completed phase 2/3 placebo-controlled studies, an open-label, long-term extension study and a randomized phase 3b/4 study. Proportions and incidence rates (IRs; unique patients with events/100 patient-years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest (AESI).
Overall, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg b.i.d.; 938 (81.1%) were in the predominant dose tofacitinib 10 mg b.i.d. group; 552 (47.7%) received tofacitinib for ≥2 years; total exposure: 3202.0 PY; 994 (85.9%) experienced AEs; 254 (22.0%) experienced serious AEs. Median treatment duration: 1.7 (range 0.0-9.2) years. IRs (95% CI) for combined tofacitinib doses: deaths 0.24 (0.10-0.48); serious infections (SIs) 1.80 (1.37-2.32); herpes zoster (HZ; non-serious and serious) 3.24 (2.63-3.94); serious HZ 0.24 (0.10-0.48); opportunistic infections 0.96 (0.65-1.36); malignancies (excluding non-melanoma skin cancer [NMSC]) 0.88 (0.59-1.26); NMSC 0.71 (0.45-1.07); major adverse cardiovascular events 0.27 (0.12-0.52); deep vein thrombosis 0.06 (0.01-0.22); pulmonary embolism 0.18 (0.07-0.40); and gastrointestinal perforations 0.09 (0.02-0.27).
Except for HZ and SIs, IRs for AESI were <1 case/100 PY. Safety was consistent with previous analyses of shorter exposure and tofacitinib's known safety profile, including real-world data.
GOV: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT03281304.
托法替布是一种用于治疗溃疡性结肠炎（UC）的口服 Janus 激酶抑制剂。我们报告了托法替布安全性的综合总结，来自已完成的全球 UC 临床项目（托法替布暴露的最长时间为 9.2 年）。
这项分析包括接受托法替布 5 或 10mg 每日两次（bid）治疗的来自完成的 2/3 期安慰剂对照研究、一项开放标签、长期扩展研究和一项随机 3b/4 期研究的患者。采用比例和发生率（IR；发生事件的独特患者/100 患者年 [PY] 的暴露）评估死亡和特别关注的不良事件（AESI）。
共有 1157 名患者接受了至少 1 剂托法替布 5 或 10mg bid；938 名（81.1%）患者接受了主要剂量托法替布 10mg bid；552 名（47.7%）患者接受了托法替布治疗≥2 年；总暴露时间：3202.0 PY；994 名（85.9%）发生了不良事件；254 名（22.0%）发生了严重不良事件。中位治疗持续时间：1.7 年（范围 0.0-9.2 年）。联合托法替布剂量的 IR（95%CI）为：死亡 0.24（0.10-0.48）；严重感染（SI）1.80（1.37-2.32）；带状疱疹（非严重和严重）3.24（2.63-3.94）；严重带状疱疹 0.24（0.10-0.48）；机会性感染 0.96（0.65-1.36）；恶性肿瘤（不包括非黑色素瘤皮肤癌 [NMSC]）0.88（0.59-1.26）；NMSC 0.71（0.45-1.07）；主要不良心血管事件 0.27（0.12-0.52）；深静脉血栓形成 0.06（0.01-0.22）；肺栓塞 0.18（0.07-0.40）；和胃肠道穿孔 0.09（0.02-0.27）。
除了带状疱疹和 SI 之外，AESI 的 IR<1 例/100 PY。安全性与之前较短暴露时间和托法替布已知安全性特征的分析一致，包括真实世界数据。
政府：NCT00787202；NCT01465763；NCT01458951；NCT01458574；NCT01470612；NCT03281304。
