Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan.
The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
Upadacitinib is a Janus kinase inhibitor with demonstrated efficacy in patients with rheumatoid arthritis (RA).
The aim of this study was to assess the long-term safety of upadacitinib in patients with active RA from Japan compared with global clinical trial populations.
Pooled data in patients enrolled from Japan (the 'Japanese population'; SELECT-SUNRISE, SELECT-EARLY, and SELECT-MONOTHERAPY) were compared with that from global (Japan and ex-Japan) upadacitinib clinical trial populations and summarized descriptively.
The Japanese population (mean age 57.0 years; mean RA duration 6.1 years) received upadacitinib 7.5 mg (n = 121), 15 mg (n = 126), and 30 mg (n = 124) once daily, while the global population (mean age 54.8 years; mean RA duration 9.1 years) received upadacitinib 6 mg twice daily/15 mg once daily (n = 2883) and 12 mg twice daily/30 mg once daily (n = 1375). Most patients were female (79.3%). The exposure-adjusted incidence rates (EAIRs) of serious adverse events in the Japanese population were 11.5, 12.2, and 21.2 per 100 patient-years (PY) with upadacitinib 7.5, 15, and 30 mg, respectively. Herpes zoster rates were higher in the Japanese population (7.8, 12.4, and 16.7 per 100 PY with 7.5, 15, and 30 mg, respectively) versus global populations (3.7 and 7.0 per 100 PY with 15 and 30 mg, respectively). Prior herpes zoster was a significant risk factor for herpes zoster.
The safety profile of upadacitinib was generally similar between Japanese and global RA populations, except for higher EAIRs for serious adverse events and infections, including herpes zoster, in the Japanese population.
SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-SUNRISE: NCT02720523; BALANCE I: NCT01960855; BALANCE II: NCT02066389.
Upadacitinib 是一种已被证明对类风湿关节炎（RA）患者有效的 Janus 激酶抑制剂。
本研究旨在比较日本和全球临床试验人群中，接受 upadacitinib 治疗的活动性 RA 患者的长期安全性。
汇总来自日本（“日本人群”）SELECT-SUNRISE、SELECT-EARLY 和 SELECT-MONOTHERAPY 研究和全球（日本和非日本）upadacitinib 临床试验人群的数据，并进行描述性总结。
日本人群（平均年龄 57.0 岁；平均 RA 病程 6.1 年）接受 upadacitinib 7.5 mg（n=121）、15 mg（n=126）和 30 mg（n=124）每日一次，而全球人群（平均年龄 54.8 岁；平均 RA 病程 9.1 年）接受 upadacitinib 6 mg 每日两次/15 mg 每日一次（n=2883）和 12 mg 每日两次/30 mg 每日一次（n=1375）。大多数患者为女性（79.3%）。日本人群中 upadacitinib 7.5、15 和 30 mg 的严重不良事件发生率（EAIR）分别为 11.5、12.2 和 21.2/100 患者年。日本人群的带状疱疹发生率高于全球人群（7.8、12.4 和 16.7/100 患者年，分别为 7.5、15 和 30 mg）。带状疱疹史是带状疱疹发生的显著危险因素。
除日本人群中严重不良事件和感染（包括带状疱疹）的 EAIR 较高外，upadacitinib 在日本和全球 RA 人群中的安全性特征总体相似。
SELECT-EARLY：NCT02706873；SELECT-NEXT：NCT02675426；SELECT-COMPARE：NCT02629159；SELECT-MONOTHERAPY：NCT02706951；SELECT-BEYOND：NCT02706847；SELECT-SUNRISE：NCT02720523；BALANCE I：NCT01960855；BALANCE II：NCT02066389。
