Siebert, S. et al. (2024) Modulation of IL‐23 signaling with guselkumab in biologic‐naïve patients versus TNF inhibitor‐inadequate responders with active psoriatic arthritis. Arthritis and Rheumatology, (doi: 10.1002/art.42803) (Early Online Publication)
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Abstract
Objective: Assess and compare immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19-subunit inhibitor, in participants with active PsA who were biologic-naïve or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR). Methods: Serum biomarker levels at baseline and following treatment with guselkumab 100 mg Q8W were compared between biologic-naïve (N=251) and TNFi-IR (N=93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS dataset. Baseline biomarker levels determined by achievement of Week-24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between subgroups. Results: Baseline IL-22, TNFα, and beta defensin (BD)-2 levels were significantly lower in biologic-naïve than in TNFi-IR participants. With guselkumab, Week-24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naïve and TNFi-IR participants (≥1.4-fold difference, nominal P<0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naïve PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P<0.05]) and trended higher in TNFi-IR ACR20 responders. Conclusion: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naïve and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses with guselkumab suggest greater dysregulation of IL-23/Th17 signaling in TNFi-IR patients.
Item Type: | Articles |
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Additional Information: | This work was funded by Janssen Research & Development, LLC, Spring House, PA, USA, and San Diego, CA, USA. |
Keywords: | Biomarkers, psoriatic arthritis, IL-23 inhibitor, guselkumab, biologics. |
Status: | Early Online Publication |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Siebert, Professor Stefan |
Authors: | Siebert, S., Coates, L. C., Schett, G., Raychaudhuri, S. P., Chen, W., Gao, S., Seridi, L., Chakravarty, S. D., Shawi, M., Lavie, F., Sharaf, M., Zimmermann, M., Kollmeier, A. P., Xu, X. L., Rahman, P., Mease, P. J., and Deodhar, A. |
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: | Arthritis and Rheumatology |
Publisher: | Wiley |
ISSN: | 2326-5191 |
ISSN (Online): | 2326-5205 |
Published Online: | 22 January 2024 |
Copyright Holders: | Copyright © 2024 The Authors |
First Published: | First published in Arthritis and Rheumatology 2024 |
Publisher Policy: | Reproduced under a Creative Commons License |
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