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

Abstract

OBJECTIVES:

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).

METHODS:

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).

RESULTS:

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.

CONCLUSION:

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.

TRIAL REGISTRATION NUMBERS:

SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.

• Authors: Stanley B Cohen, Ronald F van Vollenhoven, Kevin L Winthrop, Cristiano A F Zerbini, Yoshiya Tanaka, Louis Bessette, Ying Zhang, Nasser Khan, Barbara Hendrickson, Jeffrey V Enejosa, Gerd R Burmester
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 80 Issue 3 Pg. 304-311 (03 2021) ISSN: 1468-2060 [Electronic] England
• PMID: 33115760 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antirheumatic Agents
• Heterocyclic Compounds, 3-Ring
• upadacitinib
• Adalimumab
• Methotrexate

Topics

• Adalimumab (adverse effects)
• Antirheumatic Agents (adverse effects)
• Arthritis, Rheumatoid (chemically induced, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Herpes Zoster (chemically induced, epidemiology)
• Heterocyclic Compounds, 3-Ring (adverse effects)
• Humans
• Methotrexate (adverse effects)
• Treatment Outcome
• Venous Thromboembolism (chemically induced)