Impact of biologic class and treatment line on psoriatic arthritis risk in psoriasis: a population-based cohort study

Background Patients with psoriasis (PsO) are at increased risk of developing psoriatic arthritis (PsA). Emerging evidence suggests that biologic therapies may differentially influence the development of PsA; however, there are no data on the relative ability of second-line biological therapy to prevent PsA. Aim To evaluate the impact of biologic therapy on the risk of incident PsA in patients with PsO with a focus on second-line biologic therapy. Methods We identified 2819 patients who initiated biologic therapy for PsO between 2002 and 2022, including Tumor Necrosis Factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23p19 inhibitors and IL-12/23 inhibitors. The primary outcome was incident PsA. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate arthritis-free survival and HRs for the development of PsA. Risk was assessed separately for first-line and second-line biologic therapy. Results Among 2819 patients with PsO initiating first-line biologic therapy, 400 (14.2%) developed PsA. In multivariable Cox regression, first-line anti-IL-23p19 agents were significantly associated with a lower risk of developing PsA compared with TNF inhibitors (HR 0.13; 95% CI 0.02 to 0.96; p=0.045). Among 1246 patients receiving second-line biologics, 125 (10.0%) developed PsA. Notably, in second-line therapy, only IL-17 inhibitors were independently associated with a statistically significant reduction in PsA risk versus TNF inhibitors (HR 0.37; 95% CI 0.16 to 0.85; p=0.019), with trends observed for anti-IL-12/23 (HR 0.14; 95% CI 0.02 to 1.05; p=0.056) and anti-IL-23p19 (HR 0.46; 95% CI 0.20 to 1.07; p=0.070). Conclusions This is the first study to evaluate second-line biological therapy in relation to PsA risk. IL-17 inhibitor therapy was significantly associated with a reduced risk of incident PsA compared with TNF inhibitors.