Comparative Effectiveness and Safety of Adalimumab, Secukinumab, and Upadacitinib in Psoriatic Arthritis: A Prospective Cohort Study Based on <scp>PARWCH</scp> Cohort

Psoriatic arthritis (PsA) is a chronic inflammatory disease, with prevalence among psoriasis patients ranging from 6% to 42% across populations. Although targeted therapies such as adalimumab (ADA), secukinumab (SEC), and upadacitinib (UPA) have demonstrated efficacy in randomized controlled trials, real-world head-to-head comparisons remain limited. This study aimed to compare the real-world effectiveness and safety of ADA, SEC, and UPA in PsA patients. We conducted a prospective cohort study using data from the PARWCH database. PsA patients treated with ADA, SEC, or UPA were included and followed at baseline, Week 4, Week 12, and Week 24. Skin responses were evaluated using PASI75/90. Joint outcomes-including peripheral and axial arthritis-were assessed with ACR, PsARC, and ASAS criteria. Patient-reported pain, disease activity, and HAQ scores were also recorded. Adverse events (AEs) were monitored throughout treatment. MMRM and GLMM were used to analyze continuous and binary outcomes, respectively. A total of 187 PsA patients were included (SEC: 78; ADA: 66; UPA: 43). All three agents demonstrated comparable effectiveness in improving peripheral joint symptoms (ACR20: SEC vs. ADA, Coef = -0.29, p = 0.62; UPA vs. ADA, Coef = -0.29, p = 0.66) and axial involvement (ASAS20: SEC vs. ADA, Coef = -0.04, p = 0.81; UPA vs. ADA, Coef = -1.05, p = 0.23). UPA and SEC showed significantly greater effectiveness than ADA in improving skin lesions (PASI90: SEC vs. ADA, Coef = 1.84, p = 0.006; UPA vs. ADA, Coef = 1.53, p = 0.04). However, ADA was more effective in relieving pain compared to both UPA (Coef = 2.43, p < 0.001) and SEC (Coef = 1.21, p = 0.02). Over 24 weeks, 85 AEs were reported by 48 patients, with fatigue, rash, upper respiratory tract infection, and pruritus being the most common. No serious AEs occurred. In conclusion, UPA and SEC demonstrated balanced effectiveness across skin and joint domains, while ADA offered superior pain relief. These findings support personalized treatment strategies tailored to the clinical features of PsA patients.