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Abstract Number: 1038

Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Ankylosing Spondylitis

Arthur Kavanaugh1, Xenofon Baraliakos2, Sheng Gao3, Warner Chen3, Kristen Sweet3, Soumya Chakravarty4, Qingxuan Song3, May Shawi5, Frank Behrens6 and Proton Rahman7, 1University of California San Diego, San Diego, CA, USA, San Diego, CA, 2Rheumazentrum Ruhrgebiet Herne, Herne, Germany, 3Janssen Research and Development, LLC, Spring House, PA, 4Janssen Scientific Affairs, LLC; Drexel University College of Medicine, Villanova, PA, 5Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, 6Rheumatology University Hospital & Fraunhofer Institute Translational Medicine and Pharmacology, Goethe-University Frankfurt, Frankfurt Am Main, Germany, 7Memorial University, St. John's, NL, Canada

Meeting: ACR Convergence 2022

Keywords: Ankylosing spondylitis (AS), genetics, Psoriatic arthritis

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Session Information

Date: Sunday, November 13, 2022

Session Title: Spondyloarthritis Including PsA – Treatment Poster II: Mixed

Session Type: Poster Session B

Session Time: 9:00AM-10:30AM

Background/Purpose: Despite overlapping symptoms, axial psoriatic arthritis (axPsA) and ankylosing spondylitis (AS) may be distinct disorders with differing clinical manifestations, genetic associations, and radiographic findings.1 While guselkumab (GUS), a human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, improved symptoms of axPsA,2 risankizumab, a humanized monoclonal antibody targeting the IL-23p19 subunit, did not show improvement in the primary endpoint of proportion of AS patients (pts) achieving an ASAS40 response at week (W) 12.3 A better understanding of the molecular distinctions between axPsA and AS is needed to differentiate these diseases and guide treatment choice.

Methods: Whole blood and serum samples were collected from consenting pts in the NCT03162796/NCT0315828 studies of GUS in PsA and the NCT02437162/NCT02438787 studies of ustekinumab in AS. Human leukocyte antigen (HLA) genotypes were determined by RNA sequencing, limited to Caucasian pts to reduce genetic variability,4 and select serum cytokine levels were analyzed alongside samples from healthy individuals. Differential prevalence of HLA alleles in axPsA vs AS was determined using a Fisher’s Exact test. Statistical significance of differential baseline (BL) serum cytokine expression among axPsA vs non-axPsA vs AS pts, and of GUS effect on serum cytokine reduction vs placebo among axPsA and non-axPsA pts, were determined with a generalized linear model performed on log2-transformed data. Biomarker data from GUS every-4-weeks and every-8-weeks treatment arms were pooled.

Results: Among 186/234 Caucasian axPsA/AS pts with available data, 34%/15% were female, 70%/14% used methotrexate at BL, mean serum CRP levels were 2.8/2.4 mg/dL, and mean BASDAI scores were 6.4/7.5, respectively. Aside from race, BL demographics and disease characteristics were representative of the overall population. The prevalence of class I HLA allele -B27, -C01, and -C02 carriers was significantly lower in axPsA than AS pts (30.7% vs 92.3%, p< 0.001; 5.9% vs 31.6%, p< 0.001; and 28.0% vs 62.0%, p< 0.001, respectively), while the prevalence of HLA-C06 was significantly higher in axPsA than AS populations (36.0% vs 8.6%, p< 0.001). BL serum levels of IL-17A and IL-17F were significantly higher in axPsA (N=71) than in AS (N=58) pts (p< 0.01 and p< 0.001, respectively). Comparable IL-17A/IL-17F expression was seen for axPsA and non-axPsA (N=229) pts (both p=NS). Significant and comparable reductions from BL in serum IL-17A/IL-17F in axPsA and non-axPsA pts were seen with GUS treatment (axPsA N=41, non-axPsA N=160) vs placebo (axPsA N=30, non-axPsA N=69) at W4/24 (all p< 0.05).

Conclusion: Adults with axPsA and AS exhibit different genetic risk factors and serum IL-17 levels, supporting the concept of distinct disorders. GUS demonstrated significant pharmacodynamic effects in axPsA pts that aligned with such effects in non-axPsA pts, consistent with observed clinical improvement.2

References:
1. Feld et al. Nat Rev Rheumatol. 2018;14(6):363-371.
2. Mease et al. Lancet Rheumatol. 2021;3(10)E715-E723.
3. Baeten et al. Ann Rheum Dis. 2018;77(9):1295-1302.
4Buchkovich et al. Genome Med. 2017;9(86).


Disclosures: A. Kavanaugh, Abbvie, Amgen, Bristol-Myers Squibb(BMS), Eli Lilly, Genentech, Janssen, Merck, Novartis, Pfizer, UCB; X. Baraliakos, AbbVie, Lilly, Galapagos, MSD, Novartis, Pfizer, UCB, Bristol-Myers Squibb, Janssen, Roche, Sandoz, Sanofi; S. Gao, Janssen Research & Development, LLC; W. Chen, Janssen Research & Development, LLC, Johnson & Johnson; K. Sweet, Janssen Research & Development, LLC, Johnson & Johnson; S. Chakravarty, Janssen Scientific Affairs, LLC, Johnson & Johnson; Q. Song, Janssen Research & Development, LLC, Johnson & Johnson; M. Shawi, Janssen Pharmaceutical Companies of Johnson and Johnson; F. Behrens, AbbVie, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Bristol-Myers Squibb(BMS), Galapagos, Gilead, UCB, Affibody, MoonLake, GlaxoSmithKlein(GSK); P. Rahman, Janssen, Novartis, AbbVie, Eli Lilly and Company, Pfizer.

To cite this abstract in AMA style:

Kavanaugh A, Baraliakos X, Gao S, Chen W, Sweet K, Chakravarty S, Song Q, Shawi M, Behrens F, Rahman P. Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/genetic-and-molecular-distinctions-between-axial-psoriatic-arthritis-and-ankylosing-spondylitis/. Accessed January 30, 2023.
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