Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease with a broad clinical spectrum. PsA can affect the axial skeleton, peripheral joints, entheses, synovial sheaths of tendons, skin, nails and extra-articular organs. Tumour necrosis factor alpha blockers (TNF blockers) were a breakthrough development in the treatment of PsA. Identifying predictors of response to biological therapies in patients with PsA is of utmost importance, especially in view of the costs and potential side effects of these agents. The aims of the present study were to determine baseline predictive factors of response to biological therapies, at 3 and 6 months, in PsA patients with polyarticular involvement (with or without axial involvement). Data were collected from the Rheumatic Diseases Portuguese Register (Reuma.pt). Eligible patients had to be anti-TNF-naive at baseline and to have at least 3 months of follow-up after the beginning of TNF blocker therapy. Only patients with information on at least one of the response measures (at 3 or 6 months of follow-up) were included in the analysis. Univariable logistic regression analysis of potential baseline predictors of European League Against Rheumatism (EULAR) good clinical response, EULAR good/moderate response, 28-joint Disease Activity Score with three variables including the erythrocyte sedimentation rate (DAS28-3V-ESR) remission and Health Assessment Questionnaire (HAQ) response were performed. Multivariable logistic regression using a forward selection procedure was used until the best-fit model was obtained, taking confounding effects into account. A total of 180 patients were eligible for the study (mean age 52 years, 54% women). In multivariable analysis at 3 months, females were less likely to attain a good EULAR response [OR=0.082 (95% CI=0.024, 0.278)], a DAS28-3V-ESR remission [OR=0.083 (95% CI=0.017, 0.416)], a moderate or good EULAR response [OR=0.091 (95% CI=0.011, 0.091)] and a HAQ response [OR=0.074 (95% CI=0.009, 0.608)]. At 6 months, female gender was also less likely to achieve a good EULAR response [OR=0.060 (95% CI=0.011, 0.325)], DAS28-3V-ESR remission [OR=0.060 (95% CI=0.012, 0.297)], and a HAQ response [OR=0.138 (95% CI= 0.029, 0.654)]. In this study we found that gender was the most consistent predictor of response to TNF blocker therapy in patients with polyarticular PsA, with females having a lower probability of response compared to males. These findings suggest that gender-related biochemical, hormonal and psychological factors could play an important role in the response to TNF blocker therapy in PsA.