Background: Identifying patient characteristics that predict treatment response in psoriatic arthritis (PsA) is valuable for optimising a treat-to-target approach. Previous studies have suggested that men with PsA respond better to biologic disease-modifying anti-rheumatic drugs (bDMARDs), including secukinumab, an interleukin 17A inhibitor, compared to women. However, whether predictors of secukinumab effectiveness differ by sex remains unknown.

Objectives: To explore whether predictors of secukinumab effectiveness differ between men and women with PsA in routine clinical care across Europe.

Methods: We used data from 14 registries in the European Spondyloarthritis Research Collaboration Network (EuroSpA). Patients aged ≥18 years, diagnosed with PsA, and initiating secukinumab treatment in routine care between January 2015 and January 2021 were included. Treatment outcomes were 1) low disease activity (LDA) defined as a Disease Activity index for PsA using 28 joints (DAPSA28) ≤14 at 6 months, and 2) secukinumab discontinuation within 12 months. Multiply imputation by chained equations (35 imputed datasets) was used to impute missing baseline covariates and DAPSA28 at 6 months to account for attrition. Sex-stratified analyses were performed by logistic and Cox regression analyses to identify baseline predictors of DAPSA28 LDA at 6 months and 12-months’ secukinumab discontinuation, respectively. Potential predictors and statistical confounders were evaluated using purposeful selection [1].

Results: The cohort comprised 1,201 men and 1,589 women. At baseline, men exhibited a higher comorbidity burden, whereas women reported higher scores on patient-reported disease activity outcomes (Table 1). In men, a greater number of previous bDMARDs significantly predicted both lower odds of achieving DAPSA28 LDA at 6 months (odds ratio (OR)=0.83, 95% confidence interval (CI): 0.74-0.92) and higher risk of 12-month’s secukinumab discontinuation (hazard ratio (HR)=1.13, 95%CI: 1.04-1.23) (Table 2). Additionally, elevated C-reactive protein (CRP >10mg/L) predicted DAPSA28 LDA achievement in men (OR=1.61, 95%CI: 1.09-2.36). In women, a higher baseline fatigue score predicted greater risk of 12-months’ secukinumab discontinuation (HR=1.10, 95%CI: 1.01-1.19) (Table 2). In both men and women, pain and Health Assessment Questionnaire scores, and tender joint count using 28 joints, were predictors associated with lower odds of DAPSA28 LDA at 6 months, while psoriasis predicted lower risk of secukinumab discontinuation within 12 months (Table 2).

Conclusion: While men and women with PsA shared most baseline predictors of secukinumab effectiveness, previous bDMARD therapy and CRP>10mg/L emerged as predictors specific to men, whereas a higher baseline fatigue score was unique to women. These findings highlight the importance of sex-specific considerations for optimizing patient selection and personalized management strategies in routine care of patients with PsA treated with secukinumab.

REFERENCES: [1] Bursac et al. (2008). Source Code Biol Med 3, 17.

Acknowledgements: The EuroSpA collaboration has been supported by Novartis Pharma AG since 2017 and UCB Biopharma SRL since 2022. No financial sponsors had any influence on the study.

Disclosure of Interest: Jette Heberg Novartis (paid to employer) UCB (paid to employer), Stylianos Georgiadis Research grant from Novartis, UCB, Zohra Faizy Ahmadzay Research grant from Novartis (payed to the employer), Bente Glintborg Research grants from Pfizer, Abbvie, BMS, Sandoz, Isabel Castrejón BMS, Boehringer, Eli Lilly, Galapagos, Gebro, GSK, Janssen, Pfizer, UCB, Consultant for Alfasigma, Pfizer, UCB, Ladislav Šenolt Abbvie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Swedish Orphan Biovitrum, UCB, Abbvie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Swedish Orphan Biovitrum, UCB, Mehrdad Shoae Kazemi: None declared., Anne Gitte Loft Novartis, UCB, Janssen, Novartis, UCB, Brigitte Michelsen Speaker’s fees from Novartis, Research grant from Novartis and Pfizer (paid to employer). Centre for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328657), Simon Horskjær Rasmussen Research grant from Novartis, Gary J. Macfarlane Research grant from GSK, Karin Laas Abbvie, Johnson and Johnson, Novartis, Pfizer, Sigrid Vorobjov: None declared, Fernando Sánchez-Alonso: None declared, Ziga Rotar Abbvie, Amgen, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Abbvie, Novartis, Eli Lilly, Pfizer, Janssen, Sobi, Swixx BioPharma, AstraZeneca, Katja Perdan Pirkmajer Abbvie, Novartis, MSD, Medis, Eli Lilly, Pfizer, Lek, Sobi, Boehringer Ingelheim, Abbvie, Novartis, Medis, Eli Lilly, Pfizer, Boehringer Ingelheim, Stada, Sobi, Bjorn Gudbjornsson: None declared, Gerdur Grondal: None declared, Catalin Codreanu AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Sandoz, Sobi, “AbbVie, Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Sobi”, Florenzo Iannone consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Research grant from BMS, Galapagos, Pfizer, Fabiola Atzeni: None declared, Heřman Mann Sobi, Speakers bureau: AbbVie, Novartis, Janssen, UCB, Eli Lilly, Sobi, Abbvie, Dan Nordström Novartis, Pfizer, UCB, BMS, Lilly, MSD, Pfizer, UCB, MSD, Anna-Mari Hokkanen Grant/research support from MSD, Jorge Machida Cantante Jorge Machida Cantante: None declared, Filipe Barcelos: None declared, Pawel Mielnik Galapagos, Tore K. Kvien Grünenthal, Sandoz, UCB, AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Galapagos, AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB (to the institution), Gökçe Kenar: None declared, Marleen G.H. van de Sande Speakers fee: Novartis, UCB, Janssen, Eli Lily, Consultant for Novartis, Abbvie, Janssen, UCB, Grant/research support: UCB, Janssen, Novartis, Michael J. Nissen Speaker fees from AbbVie, Amgen, Eli Lilly, Janssens, Novartis, Pfizer, Consulting fees from AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Research grants from Novartis, Pfizer, Burkhard Moeller Eli Lilly, Janssen, Novartis, Pfizer, Amgen, Tor Olofsson MSD, UCB, Johan K Wallman Speaker fees from AbbVie, Amgen, Research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Merete Lund Hetland Speaker for Pfizer, Medac, Sandoz (no personal income, institution); speaker for Novartis (personal income), Advisory Board Abbvie (No personal income, paid to institution). Prev. chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies, Research grants (institution) from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk, Mikkel Østergaard Abbvie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Abbvie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, AbbVie, Amgen, BMS, Merck, Celgene, Eli Lilly, Novartis, UCB, Lykke Midtbøll Ørnbjerg Research grant from Novartis.

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