Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme.

This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA). Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks). 3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups. In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab. SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.

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Competing interests: SBC received grants and consultation fees from Amgen, AbbVie, Boehringer Ingelheim, Gilead, Pfizer, Roche and Sandoz. RFvV received grants from AbbVie, Arthrogen, BMS, GSK, Lilly, Pfizer and UCB and personal fees from AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche and UCB. KLW received consulting fees and research grants from AbbVie, BMS, Lilly, Pfizer, Roche and UCB. CAFZ received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche, participated on advisory boards and speaker’s bureau for Merck, Pfizer, and Sanofi-Aventis and served as a consultant for Pfizer. YT received speaking fees and/or honoraria from AbbVie, Asahi-Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Gilead, GSK, Janssen, Lilly, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi and YL Biologics and received research grants from Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda and UCB. LB received speaking fees, consulting fees and research grants from AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB. YZ, NK, BH and JVE are full-time employees of AbbVie and may hold AbbVie stock or stock options. GRB received speaking or consulting fees from AbbVie, Gilead, Janssen, Lilly, MSD, Pfizer, Roche and UCB.