OBJECTIVE: Methotrexate (MTX) is widely used as first-line treatment in psoriatic arthritis (PsA). Despite the variable efficacy of MTX in PsA compared to newer therapeutic agents, its affordability and availability make it crucial, especially in resource-limited healthcare settings. Identification of factors associated with MTX non-response could facilitate early redirection to more effective therapy. This study aimed to identify baseline clinical, demographic, and psychosocial variables associated with non-response 3 months after MTX initiation in a real-world, treatment-naïve PsA patient cohort. METHOD: Recently diagnosed, disease-modifying anti-rheumatic drug-naïve PsA patients were included. Treatment response was defined by attaining minimal disease activity 3 months after initiation of MTX monotherapy. A multivariate logistic regression analysis was performed, including sensitivity analysis. Missing variables were imputed through multiple imputations. RESULTS: In total, 287 patients were included, of whom 199 (69%) were non-responders. The median dose of MTX was 19.5 (interquartile range 15-25) mg/week. Worse baseline functioning (Health Assessment Questionnaire) [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.13-0.60], higher tender joint count in 68 joints (OR 0.91, 95% CI 0.84-0.97), and higher depression scores (Hospital Anxiety and Depression Scale) (OR 0.88, 95% CI 0.78-0.99) were associated with a lower response rate to MTX at 3 months. CONCLUSION: Our findings highlight the need for a comprehensive approach to managing patients with PsA. This involves addressing modifiable risk factors, such as depression, alongside controlling PsA disease activity. Further research is warranted to evaluate whether this integrated strategy could improve treatment efficacy and overall patient outcomes.