IMPACT study: large real-world evaluation of guselkumab in psoriatic arthritis integrating clinical response and treatment persistence

Background: In psoriatic arthritis (PsA), real-world evidence complements randomised controlled trials by evaluating treatment effectiveness in routine care. Guselkumab (GUS), a selective interleukin-23p19 inhibitor, has demonstrated efficacy in phase-III trials, but real-world data remain limited. Objectives: To assess the real-world effectiveness, treatment persistence and safety of GUS in a large, multicentre PsA cohort. Design: IMPACT (Italian Multicentric PAtient-Centred assessment of Guselkumab Treatment) is a multicentre, observational, longitudinal study including consecutive adult patients with PsA treated with GUS. Methods: Clinical assessments were conducted at baseline and at 3, 6, 9 and 12 months. Effectiveness outcomes included the change from baseline in Disease Activity in Psoriatic Arthritis (DAPSA), Axial Spondyloarthritis Disease Activity Score (ASDAS) and Psoriasis Area Severity Index (PASI) scores, as well as the resolution of enthesitis and dactylitis, and treatment persistence. Predictors of DAPSA remission and treatment discontinuation were analysed using multivariable Cox regression models. Results: A total of 389 patients were included (245 (63.0%) female; median age 56.0 years), with moderate-to-high baseline disease burden and prevalent prior biologic (b-)/targeted synthetic disease-modifying anti-rheumatic drugs (DMARD) exposure (86.4%). Median DAPSA decreased from 24.2 at baseline to 10.5 at 12 months, with significant improvements from 3 months onward. The proportion of patients achieving DAPSA-low disease activity, or -remission increased progressively, reaching up to 58.6% (187/319) and 14.1% (45/319), respectively, at 12 months. Improvements were observed across multiple disease domains, including skin involvement (PASI-100 in 123/182 (67.6%) at 12 months), enthesitis and dactylitis (12-month resolution in 118/186 (63.4%) and 57/60 (95.0%), respectively) and axial disease (ΔASDAS −1.7 at 12 months). Treatment persistence was 78.7% at 12 months, with discontinuations mainly due to ineffectiveness; age, sex, fibromyalgia, baseline disease activity, prior b/tsDMARD exposure and corticosteroid use were associated with remission and/or discontinuation. Few adverse events were recorded, with no unexpected safety signals. Conclusion: In this large real-world cohort, GUS demonstrated sustained effectiveness in several disease domains, favourable treatment persistence and no unexpected safety signals, supporting its use in routine care of complex and b/tsDMARD-experienced PsA patients.