Skin Clearance and High-Impact Area Response in the POSITIVE Study

Real-world evidence plays a critical but sometimes undervalued role in building clinical confidence around biologic therapies. Francisco Kerdel, MD, FAAD, of Florida Academic Dermatology Center, explains that while randomized controlled trials establish efficacy through carefully selected patient populations, real-world studies capture the broader, unfiltered mix of patients seen in everyday practice—including those with comorbidities or characteristics that would have excluded them from a phase 3 program. The POSITIVE study, which followed 785 patients over 2 years, represents an unusually robust real-world dataset and provides meaningful validation for tildrakizumab's efficacy in a population that more closely reflects clinical reality.

The skin clearance outcomes in POSITIVE were notable. Mean PASI scores fell from 12.9 at baseline—a level consistent with severe disease, accounting for lesion thickness, redness, scaling, and total body surface involvement—to 1.3 at year 2. Nearly 88% of patients achieved PASI ≤3 and 65% achieved PASI ≤1 at month 24, values that Kerdel characterizes as approaching complete clearance. He emphasizes that a shift of this magnitude is not cosmetic; it reflects a significant reduction in disease burden across all dimensions that the PASI captures.

Beyond overall skin clearance, POSITIVE also documented strong and sustained responses in high-impact areas: scalp, palmoplantar regions, and nails. Kerdel highlights the methodological value of examining these areas in a real-world prospective study rather than in a post hoc extraction from a larger phase 3 cohort. Prospective high-impact area analyses tend to enroll the most affected patients for that specific presentation, lending additional rigor and clinical meaning to the findings. Sustained drug survival over 2 years further reinforced the durability of response—a key consideration for a chronic condition like psoriasis.