Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Medicine, Griffith University, Brisbane, Queensland, Australia.
RMD Open. 2021 May;7(2). doi: 10.1136/rmdopen-2021-001595.
To analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.
The analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.
13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the 'infections and infestations' System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.
The tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.
分析托法替布在类风湿关节炎（RA）、银屑病关节炎（PsA）、溃疡性结肠炎（UC）和银屑病（PsO）临床研究项目中的特殊关注不良事件（AE），并确定这些事件的发生率（IR；每 100 名患者-年中出现事件的独特患者数）在不同疾病间是否一致。
该分析纳入了来自接受 ≥1 剂托法替布治疗的患者数据，这些患者来自于 RA（23 项研究）、PsA（3 项研究）、UC（5 项研究）和 PsO（7 项研究）的 1 期、2 期、3 期或 3b/4 临床试验以及长期扩展（LTE）研究（共 38 项研究）。除了一项正在进行的 UC LTE 研究（数据截止日期为 2019 年 5 月）外，所有研究均在 2019 年 7 月前完成。采用特殊关注 AE 的 IR 来评估安全性。
该分析共纳入了 13567 例患者（RA：n=7964；PsA：n=783；UC：n=1157；PsO：n=3663），共 37066 患者-年暴露于托法替布。最长暴露时间为 10.5 年（RA）。在所有疾病中，“感染和寄生虫感染”系统器官分类中的 AE 最为常见。在特殊关注的 AE 中，带状疱疹（非严重和严重；RA、PsA、UC 和 PsO 的 IR 分别为 3.6、1.8、3.5 和 2.4）和严重感染（RA、PsA、UC 和 PsO 的 IR 分别为 2.5、1.2、1.7 和 1.3）的 IR 最高。按年龄和性别校正后的死亡率比值（按国家加权）在各队列中均≤0.2。
与之前的分析相比，这项分析中托法替布的安全性概况在不同疾病间以及随着随访时间的延长保持一致。
