Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

Sweet, K., Song, Q., Loza, M. J., McInnes, I. B. , Ma, K., Leander, K., Lakshminarayanan, V., Franks, C., Cooper, P. and Siebert, S. (2021) Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials. RMD Open, 7(2), e001679. (doi: 10.1136/rmdopen-2021-001679) (PMID:34011674) (PMCID:PMC8137258)

Abstract

Objective: To investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment. Methods: Participants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies. Serum levels of acute phase reactants C reactive protein (CRP) and serum amyloid A (SAA) and inflammatory cytokines/chemokines were measured at weeks 0, 4 and 24 in 300 study participants and 34 healthy controls (HCs). The PSUMMIT studies measured serum interleukin (IL)-17A, IL-17F and CRP after ustekinumab treatment and levels with ustekinumab versus guselkumab treatment were compared. Results: Baseline serum levels of CRP, SAA, IL-6, IL-17A and IL-17F were elevated in participants with active PsA vs HCs (p<0.05, geometric mean (GM) ≥40% higher). Baseline T-helper cell 17 (Th17) effector cytokines were significantly associated with baseline psoriasis but not joint disease activity. Compared with placebo, guselkumab treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F and IL-22 as early as week 4 and continued to decrease through week 24 (p<0.05, GM decrease from baseline ≥33%). At week 24, IL-17A and IL-17F levels were not significantly different from HCs, suggesting normalisation of peripheral IL-23/Th17 axis effector cytokines postguselkumab treatment. Reductions in IL-17A/IL-17F levels were greater in guselkumab-treated versus ustekinumab-treated participants, whereas effects on CRP levels were similar. Conclusion: Guselkumab treatment reduced serum protein levels of acute phase and Th17 effector cytokines and achieved comparable levels to those in HCs. In participants with PsA, reductions of IL-17A and IL-17F were of greater magnitude after treatment with guselkumab than with ustekinumab.

• Item Type: Articles
• Additional Information: Study funded by Janssen Research and Development.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Siebert, Professor Stefan
• Authors: Sweet, K., Song, Q., Loza, M. J., McInnes, I. B., Ma, K., Leander, K., Lakshminarayanan, V., Franks, C., Cooper, P., and Siebert, S.
• 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: RMD Open
• Publisher: BMJ Publishing Group
• ISSN: 2056-5933
• ISSN (Online): 2056-5933
• Published Online: 19 May 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in RMD Open 7(2): e001679
• Publisher Policy: Reproduced under a Creative Commons License