Although biologics have revolutionized psoriasis treatment, they pose a significant burden on the healthcare budget. With the wide range of biologics available and the increasing number of biosimilars, insights into the real-world cost per responder (CPR) are required. Therefore, this study aims to evaluate the real-world CPR of adalimumab, ustekinumab, IL17- and IL23-inhibitors, incorporating both relative (Psoriasis Area and Severity Index; PASI75/90/100) and absolute (PASI ≤ 3/ ≤ 1) responder definitions and real-world dose adjustments. Tildrakizumab and bimekizumab were excluded due to limited data. Using Dutch list prices and discounts on adalimumab's and ustekinumab's originator prices because of biosimilar availability, adalimumab showed the lowest 1-year CPR across all responder definitions. Among biologics without biosimilar availability, the lowest CPRs were seen for brodalumab and guselkumab. Overall, the cost-per-PASI ≤ 3-responder was, across all biologics, more homogeneous than the CPR based on relative PASIs. Similar patterns were seen when using Swedish prices, which are, in contrast to Dutch prices, transparent. The relevance of using real-world data, specifically with the use of absolute PASIs instead of relative PASIs, is shown in this study. Additionally, as price fluctuations have the biggest impact on cost-effectiveness, price transparency is essential to effectively guide physicians in selecting a cost-effective treatment strategy.