IL-17 Inhibition vs IL-23 Inhibition for Psoriatic Arthritis: An Ongoing Debate

Authors

  • Pankti Mehta, MD Gladman Krembil Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  • Vinod Chandran, MD, MBBS, DM, PhD, FRCPC Gladman Krembil Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada

DOI:

https://doi.org/10.58931/crt.2025.2262

Abstract

The interleukin-17 (IL-17) and interleukin-23 (IL-23) pathways play a central role in the pathogenesis of psoriatic disease (PsD). This review outlines the immunobiology of these cytokine pathways and summarizes the current evidence on the efficacy and safety of IL-17 and IL-23 inhibitors across PsD domains, including peripheral arthritis, axial arthritis, enthesitis, dactylitis, psoriasis, and inflammatory bowel disease (IBD). IL-17 inhibitors, which target the effector cytokines IL-17A, IL-17F, or their receptors, have demonstrated robust efficacy in psoriasis, peripheral arthritis, and axial disease. IL-23 inhibitors act upstream by targeting the p19 subunit of IL-23 and show comparable efficacy in peripheral arthritis and psoriasis, though evidence for efficacy in axial disease remains limited. While IL-17 inhibitors carry a risk of IBD exacerbation, IL-23 inhibitors are considered therapeutic options for patients with coexisting IBD. In addition, radiographic progression appears better suppressed by IL-17 inhibitors, although emerging data suggest that IL-23 blockade may offer delayed benefits. Both IL-17 and IL-23 drug classes exhibit favourable safety profiles, with clinical trials suggesting slightly better tolerability for IL-23 inhibitors. Future directions include head-to-head comparisons, biomarker-guided treatment selection, and trials assessing long-term structural outcomes. Understanding the tissue- and cell-specific effects of inhibiting these cytokine pathways is key to optimizing therapy in PsD.

Author Biographies

Pankti Mehta, MD, Gladman Krembil Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Dr. Pankti Mehta is a Clinical Fellow in Psoriatic Arthritis and Lupus at the Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University of Toronto. She is also pursuing a Master’s in Medical Science at the Institute of Medical Science, University of Toronto. She completed her specialist training in Clinical Immunology and Rheumatology at SGPGIMS, India. Her research interests include biomarker discovery and the development of outcome measures in systemic lupus erythematosus, psoriatic arthritis, and inflammatory myopathies. She serves on the Digital and Social Media Committees of Rheumatology (Oxford) and the Journal of Clinical Rheumatology, and is a member of the Research Committee of Y-GRAPPA.

Vinod Chandran, MD, MBBS, DM, PhD, FRCPC, Gladman Krembil Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada

Dr. Vinod Chandran a rheumatologist, is a clinician scientist at the Krembil Research Institute, University Health Network, and Professor of Medicine at the University of Toronto. He is an expert in psoriatic arthritis and directs the Gladman Krembil Psoriatic Arthritis Program at the Schroeder Arthritis Institute. His translational research program is focused on developing biomarker-based diagnostic and prognostic tools for psoriatic arthritis, with support by grants from the Canadian Institutes of Health Research, the National Psoriasis Foundation, the Arthritis Society, and the Krembil Foundation. He has published more than 250 papers. He is an elected member of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA- an international organization facilitating research and education on the diagnosis and treatment of psoriasis and psoriatic arthritis) Board of Directors and its Co-Vice President.

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Mehta P, Chandran V. IL-17 Inhibition vs IL-23 Inhibition for Psoriatic Arthritis: An Ongoing Debate. Can Rheumatol Today [Internet]. 2025 Aug. 28 [cited 2025 Aug. 31];2(2):4–14. Available from: https://canadianrheumatologytoday.com/article/view/2-2-Mehta_et_al

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