托法替布治疗溃疡性结肠炎：全球临床项目长达 7.8 年的安全性汇总数据综合摘要。
Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme.
机构信息
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Department of Gastroenterology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
出版信息
J Crohns Colitis. 2023 Apr 3;17(3):338-351. doi: 10.1093/ecco-jcc/jjac141.
BACKGROUND AND AIMS
Tofacitinib is an oral small molecule Janus kinase [JAK] inhibitor for the treatment of ulcerative colitis. We report an integrated summary of tofacitinib safety [exposure: ≤7.8 years] from the global clinical programme.
METHODS
Patients receiving tofacitinib 5 or 10 mg twice daily [BID] from completed phase [P]2/3 placebo-controlled studies, an open-label, long-term extension study [final data cut-off: August 24, 2020], and interim analysis of a P3b/4 study (interim data cut-off: February 20, 2020; Overall plus P3b/4 [2020] Cohort) were included. Proportions with adverse events [AEs] and serious AEs, and incidence rates [IRs; unique patients with events/100 patient-years] for deaths and AEs of special interest [AESI] were evaluated. Opportunistic infections, malignancies, major adverse cardiovascular events [MACE] and gastrointestinal perforations were adjudicated.
RESULTS
In total, 1157 patients received one or more dose of tofacitinib (mean duration: 946.9 days); 955/1157 [83%] received a predominant dose of 10 mg BID; 412/1157 [35.6%] received tofacitinib for >4 years; 992/1157 [85.7%] had AEs, 244/1157 [21.1%] had serious AEs and 134/1157 (11.6%) discontinued use due to AEs. IRs [95% confidence intervals] for all tofacitinib doses were: deaths, 0.23 [0.09-0.46]; serious infections, 1.69 [1.26-2.21]; herpes zoster [non-serious and serious], 3.30 [2.67-4.04]; opportunistic infections, 1.03 [0.70-1.46]; malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 [0.55-1.24]; NMSC, 0.73 [0.45-1.10]; MACE, 0.29 [0.13-0.55]; deep vein thrombosis, 0.03 [0.00-0.18]; pulmonary embolism, 0.19 [0.07-0.42]; gastrointestinal perforations, 0.10 [0.02-0.28].
CONCLUSIONS
AESI IRs were stable to 7.8 years and generally <2.0 in the Overall plus P3b/4 [2020] Cohort, with the exception of herpes zoster [a known risk of tofacitinib treatment]. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304JCC Topic/keyword selection: 3. Clinical trials.
背景与目的
托法替布是一种用于治疗溃疡性结肠炎的口服小分子 Janus 激酶 [JAK] 抑制剂。我们报告了来自全球临床项目的托法替布安全性综合总结[暴露：≤7.8 年]。
方法
纳入接受托法替布 5 或 10mg 每日两次 [BID] 治疗的完成的 2/3 期安慰剂对照研究、开放标签长期扩展研究[最终数据截止日期：2020 年 8 月 24 日]和 P3b/4 研究的中期分析[中期数据截止日期：2020 年 2 月 20 日；总体加 P3b/4[2020]队列]的患者。评估不良事件 [AE] 和严重 AE 的比例以及死亡和特殊关注的 AE [AESI]的发生率[IR；每 100 患者年发生事件的独特患者数]。机会性感染、恶性肿瘤、主要不良心血管事件 [MACE] 和胃肠道穿孔进行了裁决。
结果
共有 1157 名患者接受了一次或多次托法替布治疗（平均持续时间：946.9 天）；955/1157 [83%]患者接受了主要剂量的 10mg BID；412/1157 [35.6%]患者接受托法替布治疗>4 年；992/1157 [85.7%]发生 AE，244/1157 [21.1%]发生严重 AE，134/1157（11.6%）因 AE 停用。所有托法替布剂量的 IRs[95%置信区间]为：死亡，0.23[0.09-0.46]；严重感染，1.69[1.26-2.21]；带状疱疹[非严重和严重]，3.30[2.67-4.04]；机会性感染，1.03[0.70-1.46]；恶性肿瘤（不包括非黑色素瘤皮肤癌 [NMSC]），0.84[0.55-1.24]；NMSC，0.73[0.45-1.10]；MACE，0.29[0.13-0.55]；深静脉血栓形成，0.03[0.00-0.18]；肺栓塞，0.19[0.07-0.42]；胃肠道穿孔，0.10[0.02-0.28]。
结论
在总体加 P3b/4[2020]队列中，AESI 的 IRs 稳定至 7.8 年，通常<2.0，除了带状疱疹[已知与托法替布治疗相关的风险]。ClinicalTrials.gov:NCT00787202；NCT01465763；NCT01458951；NCT01458574；NCT01470612；NCT03281304 JCC 主题/关键字选择：3.临床试验。
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