POSITIVE: Tildrakizumab Has Significant Impact on QoL in Psoriatic Disease

New data from the landmark POSITIVE trial is shedding light on the potential of tildrakizumab (Ilumya) for improving quality of life in patients with psoriatic disease.

“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. This study provides valuable new insights for the dermatology community,” said Ulrich Mrowietz, MD, professor of Dermatology and founder of the Psoriasis-Center at the Department of Dermatology at University Medical Center Schleswig-Holstein, in a statement from Almirall.2

Tildrakizumab received approval from the US Food and Drug Administration in 2018 for the management of plaque psoriasis. This approval was awarded to Sun Pharmaceuticals who own the US rights to tildrakizumab. Sun Pharmaceuticals granted Almirall exclusive rights to commercialization of the agent in Europe under the name Ilumetri in 2016.3

Billed by Almirall as first real-world evidence study in dermatology to use the WHO-5 Well-Being Index as a primary endpoint, POSITIVE was a 24-month, multinational, phase IV observational trial. Of note, the trial’s design is reflective of a resolution passed at the 78th World Health Assembly titled "Skin Diseases as a Global Public Health Priority". The resolution called for a Global Action Plan focused on prevention, early detection, treatment, long-term care, and improved access of dermatologic conditions and also recognized the intersection of skin health with mental health, stigma, and social well-being.1,2

The trial, which was presented at the European Academy of Dermatology and Venereology (EADV) 2025 Congress, enrolled 785 adult patients across 9 European countries who all received tildrakizumab in addition to routine care. At baseline, the mean WHO-5 well-being score was 53.7±21.4, which investigators point out was significantly 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).1,2

By week 16, WHO-5 scores increased to 63.2 (SD, 20.5), reaching the European norm, and continued to improve through two years of treatment, surpassing population levels at 70.43 (SD, 20.1).1,2

Clinical skin outcomes improved in parallel. Mean PASI 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 values maintained over two years (1.5±2.8 at week 52 1.3 (SD, 2.3) at week 104). At 2 years, 79.0% of patients maintained PASI of 2 or less.1,2

Quality-of-life measures showed consistent benefit, with mean DLQI-R scores falling from 12.0 (SD, 7.5) at baseline to 2.1 (SD, 3.5) at week 104. Improvements were also observed in family burden, with FamilyPso scores reduced from 1.1 (SD, 0.9) at baseline to 0.6 (SD, 0.7) at week 104.1,2

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. Of note, 29.5% of patients demonstrated psycholag—a delay in psychological recovery despite rapid skin clearance.1,2

Investigators pointed out safety outcomes were favorable, with 11.1% of patients experiencing at least 1 treatment-related adverse event and no unexpected safety signals.1,2

“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, in the aforementioned statement.2 “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.”

References:

1. Mrowietz U. Long-Term Holistic Management in Psoriatic Disease: Tildrakizumab Achieves Sustained Control of Skin Manifestations, Psychological Well-being, and Partner Quality of Life - The POSITIVE Study. Presented at the European Academy of Dermatology and Venereology (EADV) 2025 Congress. Paris, France. September 17-20, 2025.

2. Sun Pharma. Almirall and Sun Pharma enter into a License Agreement for Tildrakizumab in Europe for Psoriasis. www.prnewswire.com. Published July 27, 2016. Accessed September 21, 2025. https://www.prnewswire.com/news-releases/almirall-and-sun-pharma-enter-into-a-license-agreement-for-tildrakizumab-in-europe-for-psoriasis-300304946.html

3. Almirall. Almirall Presents Long‑Term Results from First Real‑World Dermatology Study Using WHO‑5 Well‑Being Index as Primary Endpoint in the treatment of Psoriasis at EADV 2025. Business Wire. Published September 18, 2025. Accessed September 21, 2025. https://www.businesswire.com/news/home/20250917565524/en/Almirall-Presents-LongTerm-Results-from-First-RealWorld-Dermatology-Study-Using-WHO5-WellBeing-Index-as-Primary-Endpoint-in-the-treatment-of-Psoriasis-at-EADV-2025