Background <p>Calcipotriol and betamethasone dipropionate (CAL/BDP) formulations are the gold standard treatment for patients with mild to moderate plaque psoriasis. Yet, few studies have addressed the cost efficacy of these therapies in Italy. This study aims to evaluate the cost per response of CAL/BDP PAD-cream against CAL/BDP gel formulations from an Italian National Healthcare System (NHS) perspective.</p> Methods <p>A cost-per-response model was built considering three clinical measures: Physician’s Global Assessment (PGA) success (PGA &lt; 2 and with a minimum of two-point decrease from baseline), a 75% reduction in the modified Psoriasis Area and Severity Index 75 (mPASI75) and quality-adjusted life years (QALY) gained. Clinical evidence was extracted from a pooled analysis including two phase III clinical trials assessing CAL/BDP PAD-cream against gel. Sensitivity analyses were performed to test the robustness of the results, and alternative scenarios were conducted to examine specific CAL/BDP gel comparators and drug use.</p> Results <p>CAL/BDP PAD-cream showed lower costs per response than CAL/BDP gel formulations for PGA success and mPASI75. The incremental cost-effectiveness ratio was €3162.12 per QALY gained. Similar results were obtained for alternative scenarios considering the most commonly prescribed branded gel as the only comparator, or generic gel products as comparators. In an alternative scenario defining an equal amount of drug used per patient for both treatments, CAL/BDP PAD-cream turned dominant over gel formulations.</p> Conclusion <p>CAL/BDP PAD-cream is a highly efficient alternative for managing mild to moderate plaque psoriasis compared with gel formulations for the Italian NHS.</p>