The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan

Kunihiro Yamaoka, Yoshiya Tanaka, Hideto Kameda, Nasser Khan, Nobuhito Sasaki, Masayoshi Harigai, Yanna Song, Ying Zhang, Tsutomu Takeuchi, Kunihiro Yamaoka, Yoshiya Tanaka, Hideto Kameda, Nasser Khan, Nobuhito Sasaki, Masayoshi Harigai, Yanna Song, Ying Zhang, Tsutomu Takeuchi

Abstract

Introduction: Upadacitinib is a Janus kinase inhibitor with demonstrated efficacy in patients with rheumatoid arthritis (RA).

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration numbers: SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-SUNRISE: NCT02720523; BALANCE I: NCT01960855; BALANCE II: NCT02066389.

Conflict of interest statement

Kunihiro Yamaoka has received speakers bureau fees from AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd. Yoshiya Tanaka has received speaking fees and/or honoraria from AbbVie, Asahi-Kasei Pharma Corporation, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Eli Lilly Japan KK, Gilead, GlaxoSmithKline KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Novartis, Pfizer Japan Inc., Sanofi KK, and YL Biologics; and research grants from AbbVie, Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd, and UCB. Hideto Kameda has received consulting fees, speaking fees, and/or honoraria from AbbVie GK, Asahi-Kasei Pharma Corporation, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan KK, Gilead, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Novartis, Pfizer Japan Inc., Sanofi KK, and UCB Japan; and research grants from AbbVie GK, Asahi-Kasei Pharma Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Corporation, and Novartis. Nasser Khan, Nobuhito Sasaki, Yanna Song, and Ying Zhang are employees of AbbVie and may own stocks or stock options. Masayoshi Harigai has received grants from AbbVie Japan Co. Ltd, Bristol-Myers Squibb KK, Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Co., Santen Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, and Teijin Pharma, Ltd; and personal fees from AbbVie Japan Co. Ltd, Astellas Pharma Inc., Bristol-Myers Squibb KK, Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, and Teijin Pharma, Ltd. Tsutomu Takeuchi has received grants from AbbVie GK, Asahi-Kasei Pharma Corporation, Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co. Ltd, Novartis Pharma KK, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd; and personal fees from AbbVie GK, Astellas Pharma Inc., AstraZeneca KK, Bristol-Myers Squibb KK, Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Eli Lilly Japan KK, GlaxoSmithKline KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co. Ltd, Novartis Pharma KK, Pfizer Japan Inc., Sanofi KK, Teijin Pharma Ltd, Taiho Pharmaceutical Co. Ltd, Taisho Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, and UCB.

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Source: PubMed

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