Safety of guselkumab with and without prior TNF-α inhibitor treatment: pooled results across four studies in patients with psoriatic arthritis

Rahman, P. et al. (2023) Safety of guselkumab with and without prior TNF-α inhibitor treatment: pooled results across four studies in patients with psoriatic arthritis. Journal of Rheumatology, 50(6), pp. 769-780. (doi: 10.3899/jrheum.220928) (PMID:36642439)

Abstract

Objective: Assess pooled safety results through the end of the Phase 2/3 studies of guselkumab (≤2 years) in tumor necrosis factor-α inhibitor (TNFi) -naïve and -experienced patients with psoriatic arthritis (PsA). Methods: Data were pooled from the Phase 2 and DISCOVER-1 (TNFi-naïve/experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to guselkumab 100 mg every 4 or 8 weeks (Q4W+Q8W=Combined Guselkumab) or placebo with crossover to guselkumab Q4W or Q8W at Week 24. Timeadjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the placebo-controlled period and through end of study. Results: Of 1554 randomized patients (n=373 [guselkumab Q4W], 664 [guselkumab Q8W], and 517 [placebo]), 1138 (73.23%) were TNFi-naive and 416 (26.76%) were TNFi-experienced. Respective AE rates through Week 24 were 220.8/100PY (TNFi-naïve) and 251.6/100PY (TNFiexperienced) in the Combined Guselkumab group and 196.1/100PY (TNFi-naïve) and 303.0/100PY (TNFi-experienced) in the Placebo group. Among all guselkumab-treated patients (including those who crossed over from placebo), low AE rates were maintained during longterm evaluation in both TNFi-naïve (139.69/100PY) and TNFi-experienced (174.0/100PY) patients. Rates/100PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between placebo and guselkumab-treated patients through Week 24 treatment regardless of prior TNFi use and remained low through the end of the studies. Conclusion: The safety profile of guselkumab in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain
• Authors: Rahman, P., Boehncke, W.-H., Mease, P. J., Gottlieb, A. B., McInnes, I. B., Shawi, M., Wang, Y., Sheng, S., Kollmeier, A. P., Theander, E., Yu, J., Leibowitz, E., Marrache, A. M., and Coates, L. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Journal of Rheumatology
• Publisher: Journal of Rheumatology
• ISSN: 0315-162X
• ISSN (Online): 1499-2752
• Published Online: 15 January 2023
• Copyright Holders: Copyright © 2023 The Journal of Rheumatology
• First Published: First published in Journal of Rheumatology 50(6):769-780
• Publisher Policy: Reproduced in accordance with the publisher copyright policy