AbstractObjectivesWe aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA).Materials and methodsWe enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004–2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan–Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded.ResultsTwo hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50–3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07–3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22–0.73).ConclusionsSurvival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI.Key Points• Drug survival in PsA patients was confirmed be greater for the first bDMARD administered.• In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches.• Female sex may constitute a predisposing risk factor for flare and therapeutic switches.• Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.