Background/Purpose: Psoriatic arthritis (PsA) is a heterogeneous condition and sex differences in phenotypic presentation, disease trajectory, and treatment response have been reported. Nevertheless, it remains unclear whether classes of targeted therapies differentially impact men and women with PsA.

Our objective was to assess the influence of sex on the long-term persistence of each class of targeted therapies in a national healthcare database.

Methods: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database (SNDS). We included all adults with PsA, new users of targeted therapies (not in the year before the index date) during 2015-2021, and studied each different treatment line during the study. Persistence was defined as the time from treatment initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by sex involved using multivariate frailty model and adjusting on csDMARDs and prednisone as time-dependant variables. Similar analyses were performed in patients receiving first-line targeted therapy only. To control the risk of type 1 error, a Bonferroni adjustment was applied: a p≤0.01 was considered significant, and 99% confidence intervals (CI) were calculated.

Results: We included 14,778 patients with PsA new users of targeted therapies: 8,475 (57%) women (mean age 50±13 years), 6,303 (43%) men (51±13 years). The number of lines of therapy were: within women, 9,462 (60%) TNF inhibitors (TNFi), 3,762 (24%) IL17i, 1,639 (10%) IL12/23i, 392 (2%) IL23i, 576 (4%) JAKi, and within men 6,192 (59%) TNFi, 2,433 (23%) IL17i, 1,170 (11%) IL12/23i, 406 (4%) IL23i and 287 (3%) JAKi. Overall, 1-year persistence rates were 52% for women and 62% for men. Persistence decreased markedly over time in both sexes to 27% and 39% respectively at the end of the third year, although in varying proportions by therapeutic class. After adjustments, persistence was statistically lower in women than in men for TNFi (adjusted hazard ratio (HR_a) 1.4, 99%CI 1.3-1.5) and IL17i (HR_a 1.2, 99%CI 1.1-1.3), but not for IL12/23i (HR_a 1.1, 99%CI 0.9-1.3), IL23i (HR_a 1.1, 99%CI 0.7-1.5) and JAKi (HR_a 1.2, 99%CI 0.9-1.6). Results were similar for patients receiving first-line therapy (Table).

Conclusion: Treatment persistence is lower in women than in men for TNFi and IL17i, but no longer significant for IL12/23i, IL23i and JAKi. This may be due to differences in rheumatic phenotype, disease activity/severity or immunogenicity, but also to disparities in healthcare-seeking behavior due to gender norms. This highlights the need for sex- and gender-based studies to better understand the underlying mechanisms, but also for face-to-face studies with sex-stratified analyses to optimize the management of PsA patients and achieve the ambitious goal of personalized medicine in the coming years.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/influence-of-sex-on-the-persistence-of-different-classes-of-targeted-therapies-for-psoriatic-arthritis-a-cohort-study-of-14778-patients-from-the-french-health-insurance-database-snds/