OBJECTIVES: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are a major contributor to the substantial costs associated with psoriatic arthritis (PsA), a chronic inflammatory rheumatic disease associated with psoriasis. Currently there are no cost-effectiveness analyses (CEAs) comparing the interleukin-17A antagonists ixekizumab and secukinumab in Spain. A CEA was conducted from the perspective of the Spanish National Health System to compare the cost-effectiveness of ixekizumab versus secukinumab in bDMARD-naïve patients with PsA and concomitant moderate-to-severe psoriasis. METHODS: A Markov model with a lifetime horizon and monthly cycles was developed based on the widely accepted York model. The model included four health states: induction period (12 weeks), continuous treatment, best supportive care (BSC) and death. The response criterion was a combination of Psoriatic Arthritis Response Criteria and ≥90% improvement in Psoriasis Area Severity Index (PASI90). At the end of the bDMARD induction period, responders transitioned to continuous treatment with the induction bDMARD. Non-responders and patients who discontinued continuous treatment transitioned to BSC. Clinical efficacy data were derived from network meta-analyses. Health utilities were generated by applying a regression analysis to PASI and Health Assessment Questionnaire scores collected in the SPIRIT studies with ixekizumab in PsA for bDMARD-naïve patients with moderate-to-severe psoriasis. Only direct medical costs were included (year of costing 2017). RESULTS: Ixekizumab was associated with incremental reductions in costs of €5,333 and comparable gains in quality-adjusted life-years (QALYs) with a difference of 0.01 in favour of ixekizumab. Deterministic and probabilistic sensitivity analyses globally confirmed the base case results. CONCLUSIONS: Yielding comparable QALY gains at lower cost, ixekizumab is cost-effective versus secukinumab in biologic-naïve PsA patients with concomitant moderate-to-severe psoriasis in Spain.