JAK1-selective inhibitors versus pan-JAK inhibitors: comparative real-world study of drug retention in chronic inflammatory arthritis.

Background: Janus kinase inhibitors (JAKi) are effective treatments for chronic inflammatory arthritis (CIA). Tofacitinib and baricitinib are pan-JAK inhibitors, while upadacitinib and filgotinib are JAK1-selective inhibitors. Objective: This study aimed to compare retention rates between JAKi classes and identify predictors of discontinuation. Design: Retrospective observational study. Methods: We retrospectively evaluated patients with CIA (Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Spondyloarthritis (SpA)) treated with JAKis from 2017 to 2024. The independent variable was JAKi class (pan-JAK inhibitors/JAK1-selective inhibitors). Retention was assessed using Kaplan-Meier estimates, and predictors of discontinuation were evaluated through Cox multivariable regression. Results: The study included 181 patients (83% women; median age 56). Diagnoses were RA (84%), PsA (9%), and SpA (7%). A total of 227 JAKi treatment courses were analyzed: 96 JAK1-selective inhibitors and 131 pan-JAK inhibitors. Overall, 118 courses (52%) were discontinued (55% inefficacy; 42% adverse events). The discontinuation incidence rate (IR) was 35.5 per 100 patient-years, with 50% stopping treatment within 1.65 years. Discontinuation was more frequent in women, patients with cardiovascular (CV) disease or risk factors, and in PsA compared to RA. Discontinuation rates were lower for JAK1-selective inhibitors (IR: 28.6; 95% confidence interval (CI): 20.5-39.8) versus pan-JAK inhibitors (IR: 39.6; 95% CI: 31.9-49.1). Multivariate analysis confirmed that pan-JAK inhibitors, female sex, PsA, CV disease, prior targeted biological and synthetic disease-modifying drugs exposure, and leflunomide co-treatment increased the risk of discontinuation. Conclusion: Pan-JAK inhibitors may have higher discontinuation rates than JAK1-selective inhibitors in real-world CIA patients. Clinical characteristics and comorbidities should guide JAKi selection to optimize long-term treatment retention.