The landmark POSITIVE trial has revealed that tildrakizumab (Ilumya/Ilumetri) delivers comprehensive benefits beyond skin clearance, significantly improving psychological wellbeing, quality of life, and reducing family burden in patients with psoriatic disease. The 24-month, multinational phase IV observational study enrolled 785 adult patients across 9 European countries, marking the first real-world evidence study in dermatology to use the WHO-5 Well-Being Index as a primary endpoint.
Psychological Wellbeing Shows Dramatic Improvement
At baseline, patients demonstrated significantly impaired psychological wellbeing with mean WHO-5 scores of 53.7±21.4, substantially lower than the European population average of 64.9 (P <.0001) and comparable to values observed in patients with diabetes distress (51.4) or breast cancer (52.2). By week 16, WHO-5 scores increased to 63.2 (SD, 20.5), reaching European population norms, and continued improving through two years of treatment to 70.43 (SD, 20.1), surpassing population levels.
"POSITIVE takes a truly holistic approach to managing psoriasis by incorporating PROs that were previously unexplored in dermatology, such as the WHO-5 score for measuring psychological well-being and the impact of the disease on patient's partners," said Ulrich Mrowietz, MD, professor of Dermatology and founder of the Psoriasis-Center at the Department of Dermatology at University Medical Center Schleswig-Holstein.
Sustained Clinical Efficacy Demonstrated
Clinical skin outcomes improved in parallel with psychological measures. Mean PASI scores decreased from 12.9 (SD, 8.1) at baseline to 2.4 (SD, 3.3) at week 16 and 1.7 (SD, 2.7) at week 28, with sustained improvement maintained over two years (1.5±2.8 at week 52 and 1.3 (SD, 2.3) at week 104). At two years, 79.0% of patients maintained PASI scores of 2 or less.
After 16 weeks of therapy, 60.9% of patients achieved PASI scores less than 2, while 57.7% reached WHO-5 scores greater than 64, indicating good psychological well-being. Notably, the study identified that 29.5% of patients demonstrated "psycholag"—a delay in psychological recovery despite rapid skin clearance.
Quality of Life and Family Impact
Quality-of-life measures showed consistent benefit throughout the observation period. Mean DLQI-R scores fell from 12.0 (SD, 7.5) at baseline to 2.1 (SD, 3.5) at week 104. The study also demonstrated reduced family burden, with FamilyPso scores decreasing from 1.1 (SD, 0.9) at baseline to 0.6 (SD, 0.7) at week 104.
Safety Profile Remains Favorable
Safety outcomes were favorable throughout the 24-month period, with 11.1% of patients experiencing at least one treatment-related adverse event and no unexpected safety signals identified.
Regulatory and Commercial Context
Tildrakizumab, a humanized anti-IL-23p19 monoclonal antibody designed to selectively block the cytokine IL-23, received FDA approval in 2018 for plaque psoriasis management. Sun Pharmaceuticals owns US rights to the drug, while Almirall holds exclusive European commercialization rights under the name Ilumetri, granted in 2016 through a licensing agreement involving an initial $50 million upfront payment.
"Measuring psychological and physical wellbeing as primary outcomes, the POSITIVE study demonstrates comprehensively - for the first time - that patients can 'get their lives back' as a range of relevant health aspects improve with treatment," said Volker Koscielny, chief medical officer. "The study also proposes a model that looks at disease impact in a more holistic way, including the impact on people close to the patients."
The trial's design reflects a resolution passed at the 78th World Health Assembly titled "Skin Diseases as a Global Public Health Priority," which called for a Global Action Plan recognizing the intersection of skin health with mental health, stigma, and social well-being.
