Tildrakizumab in Managing Psoriasis with Involvement of Difficult-to-Treat Areas: A Multicenter Real-Life Retrospective Study

<b>Background</b>: Psoriasis involving difficult-to-treat anatomical areas, such as the scalp, genitalia, fingernails, and palmoplantar regions, carries a disproportionate disease burden and often requires systemic therapy. In this context, real-life data comparing the long-term effectiveness of tildrakizumab 100 mg versus 200 mg in patients with difficult-to-treat psoriasis remain limited. <b>Methods</b>: This multicenter retrospective observational study included adult patients in three Italian dermatology centers. Global efficacy endpoints included PASI75, PASI90, PASI100, and absolute PASI ≤ 2 at weeks 16, 32, 52, and 104. Site-specific effectiveness was assessed as complete clearance (PGA = 0) in patients with baseline involvement (PGA ≥ 2) of difficult-to-treat areas. Outcomes were described by dose. <b>Results</b>: 183 patients were included (100 mg: n = 89; 200 mg: n = 94). Patients receiving 200 mg had higher baseline BMI and were more frequently biologic-experienced. At week 104, PASI75 was achieved by 94.2% of patients receiving 100 mg and 94.7% receiving 200 mg, while PASI90 and PASI100 were achieved by 82.7% vs. 57.9% and 48.1% vs. 47.4%, respectively. Clearance of difficult-to-treat areas improved progressively across all sites. Scalp and genital psoriasis showed higher and earlier clearance rates, whereas nail and palmoplantar psoriasis showed slower and more heterogeneous responses. No consistent dose-dependent advantage emerged, despite less favorable baseline characteristics in the 200 mg group. <b>Conclusions</b>: Over 104 weeks, tildrakizumab showed sustained long-term effectiveness in both global disease control and difficult-to-treat areas. The 200 mg dose, used in a more difficult-to-treat population, achieved comparable long-term outcomes, supporting dose optimization in clinical practice.