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Abstract Number: 1373

IL-23 Skin and Joint Profiling in Psoriatic Arthritis: Novel Perspectives in Understanding Clinical Responses to IL-23 Inhibitors

Alessandra Nerviani1, Marie-Astrid Boutet1, Wang Sin Gina Tan1, Katriona Goldmann1, Nirupam Purkayastha1, Tamas Lajtos1, Rebecca Hands1, Myles Lewis1, Stephen Kelly2 and Costantino Pitzalis3, 1Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, United Kingdom, 2Mile End Hospital, Barts Health NHS Trust, London, United Kingdom, 3Queen Mary University of London, London, United Kingdom

Meeting: ACR Convergence 2020

Keywords: Interleukins, Psoriatic arthritis, skin, Synovitis

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Session Information

Date: Sunday, November 8, 2020

Session Title: Spondyloarthritis Including Psoriatic Arthritis – Treatment Poster III

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: PsA is a chronic heterogeneous inflammatory condition affecting up to 30% of patients with skin and/or nail psoriasis and the IL-23/IL-17 axis is believed to be key in psoriasis and PsA pathogenesis. Several drugs targeting the IL-23/IL-17 axis have been successfully tested in the context of psoriasis and PsA but, while 50-60% of patients achieve almost complete psoriasis clearance upon treatment, the joint disease improvement is modest. To date, the mechanism for the divergent skin-joint response remains largely unexplained. This study aims to determine the relationship between synovial versus skin transcriptional/histological profiles in patients with active PsA and to explore mechanistic links between diseased tissue pathology and clinical outcomes.

Methods: Twenty-seven patients fulfilling the ClASsification for Psoriatic ARthritis (CASPAR) criteria with active peripheral joint disease ( >3 tender and >3  swollen joints) despite an adequate trial of at least two conventional synthetic DMARDs and either biologic-naïve or failing one or more TNF-α-inhibitor (anti-TNF) were enrolled in an observational/open-label study. Patients underwent biopsies of synovium and paired lesional/non-lesional skin before starting anti-TNF (if biologic-naïve; n=18) or ustekinumab (anti-IL-12/IL-23p40; if anti-TNF inadequate responders; n=9). Molecular analysis of 80-inflammation-related genes and protein levels for IL-23p40/IL-23p19/IL-23R were assessed by real-time-PCR and immunohistochemistry, respectively.

Results: At baseline, all patients had persistent active disease as per inclusion criteria. At 16-weeks-post-treatment, skin responses favoured ustekinumab, while joint responses favoured anti-TNF therapies. Principal-component-analysis revealed distinct clustering of synovial tissue gene expression away from the matched-skin. While IL12B–IL23A-IL23R were homogeneously expressed in lesional skin, their expression was extremely heterogeneous in paired synovial tissues. Here, IL-23 transcriptomic/protein expression was strongly linked to patients with high-grade synovitis who, however, were not distinguishable by conventional clinimetric measures.

Conclusion: PsA synovial tissue shows a heterogeneous IL-23 axis profile when compared to matched skin. Synovial molecular-pathology may help to identify among clinically indistinguishable patients those with a greater probability of responding to IL-23 inhibitors.


Disclosure: A. Nerviani, None; M. Boutet, None; W. Tan, None; K. Goldmann, None; N. Purkayastha, None; T. Lajtos, None; R. Hands, None; M. Lewis, None; S. Kelly, None; C. Pitzalis, None.

To cite this abstract in AMA style:

Nerviani A, Boutet M, Tan W, Goldmann K, Purkayastha N, Lajtos T, Hands R, Lewis M, Kelly S, Pitzalis C. IL-23 Skin and Joint Profiling in Psoriatic Arthritis: Novel Perspectives in Understanding Clinical Responses to IL-23 Inhibitors [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/il-23-skin-and-joint-profiling-in-psoriatic-arthritis-novel-perspectives-in-understanding-clinical-responses-to-il-23-inhibitors/. Accessed June 29, 2022.
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