Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Radiographic Axial Spondyloarthritis: Post Hoc Analyses from Four Phase 3 Clinical Trials

Arthur Kavanaugh; Xenofon Baraliakos; Sheng Gao; Warner Chen; Kristen Sweet; Soumya D Chakravarty; Qingxuan Song; May Shawi; Proton Rahman

doi:10.1007/s12325-023-02475-4

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Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Radiographic Axial Spondyloarthritis: Post Hoc Analyses from Four Phase 3 Clinical Trials

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Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Radiographic Axial Spondyloarthritis: Post Hoc Analyses from Four Phase 3 Clinical Trials

Arthur Kavanaugh, Xenofon Baraliakos, Sheng Gao, Warner Chen, Kristen Sweet, Soumya D Chakravarty, Qingxuan Song, May Shawi and Proton Rahman

Advances in therapy, v 40(5), pp 2439-2456

01 May 2023

DOI: https://doi.org/10.1007/s12325-023-02475-4

PMID: 36995469

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Arthritis, Psoriatic - diagnostic imaging

Arthritis, Psoriatic - drug therapy

Arthritis, Psoriatic - genetics

Axial Spondyloarthritis

Humans

Ustekinumab - therapeutic use

Emerging evidence suggests psoriatic arthritis (PsA) with axial involvement (axPsA) and radiographic axial spondyloarthritis (r-axSpA) may possibly represent distinct disorders, with some differing clinical manifestations, genetic associations, and radiographic findings. Moreover, axPsA and r-axSpA may respond differently to therapies: guselkumab (interleukin [IL]-23p19 subunit inhibitor [i]) and ustekinumab (IL-12/23p40i) demonstrated improvements in axial symptoms in patients with PsA; however, neither risankizumab (IL-23p19i) nor ustekinumab demonstrated efficacy versus placebo in patients with r-axSpA. Current analyses aim to further understand potential molecular distinctions between axPsA and r-axSpA and examine the pharmacodynamic effects of guselkumab in patients with axPsA and those with PsA without axial involvement (non-axPsA). Post hoc analyses utilized biomarker data from blood and serum samples collected from a subset of participants in phase 3 studies of ustekinumab in r-axSpA and guselkumab in PsA (DISCOVER-1 and DISCOVER-2). Participants with axPsA were identified by investigator-verified sacroiliitis (imaging-confirmed) and axial symptoms. HLA mapping, serum cytokine analysis, and whole-blood RNA sequencing were conducted. Relative to r-axSpA, patients with axPsA had a lower prevalence of HLA-B27, HLA-C01, and HLA-C02 alleles and a higher prevalence of HLA-B13, HLA-B38, HLA-B57, HLA-C06, and HLA-C12 alleles. Compared with r-axSpA, patients with axPsA had elevated baseline levels of serum IL-17A and IL-17F cytokines, enrichment of IL-17 and IL-10 pathway-associated genes, and neutrophil gene markers. Across axPsA and non-axPsA cohorts, reductions in cytokine levels and normalization of pathway-associated gene expression with guselkumab treatment were comparable. The differences in HLA genetic associations, serum cytokines, and enrichment scores support the concept that axPsA and r-axSpA may be distinct disorders. The comparable pharmacodynamic effects of guselkumab on cytokine levels and pathway-associated genes observed in patients with axPsA and non-axPsA are consistent with demonstrated clinical improvements across PsA cohorts. These findings contribute to the understanding of potential genetic and molecular distinctions between axPsA and r-axSpA. ClinicalTrials.gov identifiers, NCT03162796, NCT0315828, NCT02437162, and NCT02438787.

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Details

Title: Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Radiographic Axial Spondyloarthritis: Post Hoc Analyses from Four Phase 3 Clinical Trials
Creators: Arthur Kavanaugh - University of California, San Diego
Xenofon Baraliakos - Rheumazentrum Ruhrgebiet
Sheng Gao - Janssen
Warner Chen - Janssen
Kristen Sweet - Janssen
Soumya D Chakravarty - Drexel University, General Internal Medicine
Qingxuan Song - Janssen Research & Development, LLC, Spring House, PA, USA
May Shawi - Janssen
Proton Rahman - Memorial University of Newfoundland
Publication Details: Advances in therapy, v 40(5), pp 2439-2456
Publisher: Springer Nature
Number of pages: 18
Resource Type: Journal article
Language: English
Academic Unit: Rheumatology; General Internal Medicine
Web of Science ID: WOS:000960842700002
Scopus ID: 2-s2.0-85151327737
Other Identifier: 991021861288604721

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Web of Science research areas: Medicine, Research & Experimental; Pharmacology & Pharmacy