OBJECTIVES: Biologic therapies have proven efficacious for patients with moderate-to-severe psoriasis. However, recommended therapeutic regimens and modes of administration differ from agent to agent. For Italy, their economic value compared with standard of care has not been explored. This study estimates the cost-effectiveness of intermittent therapy with etanercept in patients with moderate-to-severe plaque-type psoriasis in comparison with non-systemic therapy in Italy. METHODS: This study employs cost-utility analysis using a Markov model adapted from the British “York model”. It compares intermittent etanercept vs non-systemic therapy in terms of cost per Quality-Adjusted Life Year (QALY). Data on efficacy and changes in quality of life were derived from three etanercept clinical trials. Direct costs of treating psoriasis patients, including hospitalizations and dermatology clinic visits, were taken from an Italian cost-of-illness study. Extrapolations were made to evaluate the cost-effectiveness of intermittent etanercept vs non-systemic therapy over a period of ten years. RESULTS: For the group of patients with moderate and severe plaque psoriasis (initial Psoriasis Area and Severity Index PASI≥10) the incremental cost-effectiveness ratio (ICER) for etanercept compared with non-systemic therapy was €33,216/QALY; for the group of patients with severe psoriasis (PASI≥20), the ICER was €25,486/QALY. CONCLUSIONS: Within the Italian health care system, intermittent etanercept (25 mg twice weekly) is a cost-effective therapeutic option compared with non-systemic therapy for the group of patients with moderate and severe plaque psoriasis. For patients with PASI ≥20 etanercept cost-effectiveness is even greater.