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PARIS — A psoriasis treatment trial using a patient-centered outcome as the primary endpoint supports a World Health Organization (WHO) initiative to measure therapeutic benefit in chronic diseases more holistically, capturing mental and physical recovery, not just control of the underlying pathology.

Already commonly used in cancer trials, this approach “establishes a new paradigm for value-based dermatological care,” according to the principal investigator, Ulrich Mrowietz, MD, professor of dermatology and head of the Psoriasis Center at the University Medical Center Schleswig-Holstein, Kiel, Germany.

Patient-Reported Outcome Evaluates Well-Being

The study, called POSITIVE, employed a patient-reported outcome as a primary endpoint in a multinational plaque psoriasis trial for the first time, according to Mrowietz. The goal was to evaluate recovery 2 years after initiating therapy with the interleukin-23 inhibitor tildrakizumab, which is approved for treating moderate-to-severe psoriasis in the US and other countries.

The results of the trial were presented as a late breaker at European Academy of Dermatology and Venerology (EADV) 2025 Congress.

The outcomes on the five-point patient-completed WHO-5 Well-Being Index that assesses psychological well-being were instructive, Mrowietz reported.

From a WHO-5 mean baseline score of 53.7, a level comparable to scores associated with breast cancer and diabetes, the scores at 16 weeks climbed to a mean of 63.2, which is only slightly below the mean score of 64.0 for a healthy European general population, Mrowietz noted. During this time, the mean Psoriasis Area and Severity Index (PASI) score had fallen to a mean of 1.7 at 28 weeks from a baseline of 12.9.

With further follow-up, the mean WHO-5 score climbed to 65.9 at 52 weeks, which Mrowietz indicated is meaningfully higher than that typical of a healthy population. Mean PASI scores also improved, falling to 1.5 and 1.3 at 1 year and 2 years, respectively.

“We interpret the higher than average score as a consequence of the relief patients experience from sustained control from a chronic disease,” Mrowietz reported. At 2 years, the mean WHO-5 score was 70.43.

Even though the improvement in PASI score and the climb on the well-being score tracked together, 29.5% of patients had a delayed WHO-5 recovery score at 16 weeks despite skin clearance. This is significant because it highlights a “complex relationship between physical and mental health recovery,” Mrowietz said. He attributed the delay to persistent anxiety that the disease would relapse.

In addition to WHO-5 and PASI scores, the 785 patients with moderate-to-severe psoriasis participating in this phase 4 observational trial were also followed with the Dermatology Life Quality Index-Relevant (DLQI-R).

The study was undertaken as a response to a WHO initiative to emphasize patient-centered healthcare in all chronic diseases, according to Mrowietz, but he added that chronic dermatological diseases were mentioned specifically.

For the clinical approach to patients, “the question is being redirected from ‘what is the matter with you’ to ‘what matters to you’ in regard to controlling disease,” Mrowietz explained.

Partner’s Experience Also Evaluated

Within this initiative and reflected in the POSITIVE trial, attention to partner and family well-being is considered an important part of patient well-being. Mrowietz and study coauthors reported some of the results from the POSITIVE trial in Psoriasis: Targets and Therapy several months prior to the EADV meeting and believe these secondary results are also important.

“We did see an improvement in WHO-5 scores over the course of the 2 years, but the recovery was slower in partners than patients,” Mrowietz reported. He believes that this reflects persistent concern among partners, as measured by the FamilyPso questionnaire, that the improvement will prove transient. Further analysis is planned.

One potential message from these initial results is that partners should be encouraged to accompany patients to clinic visits, he said. In addition to the fact that an accompanying individual can reinforce the information provided to the patient, they might also derive reassurance from hearing and understanding the treatment plan, he added.

“It is possible that an unsupportive anxious partner might have a negative effect, which is something worth considering, but often the support provided by the partner can help with adherence to the treatment strategy,” Mrowietz said.

One notable attribute of the WHO-5 is that it is designed purposefully to focus on positive rather than negative variables. Unlike most patient questionnaires that focus on the severity of symptoms, the WHO-5 asks patients (and partners) to agree or disagree with such statements as “I feel cheerful and in good spirits” or “I have felt calm and relaxed” subsequent to treatment. This is the oppositive of such tools as the DLQI-R that frames questions from a negative direction, Mrowietz said.

One of the advantages of a holistic approach to judging therapeutic benefit is that it focuses on a global sense of change, and considerations beyond disease control, including the degree to which treatment has relieved the burden of having a chronic disease, is captured, he said.

This is particularly useful for judging clinical benefits in a chronic disease that can be controlled without cure.

“We need to establish what matters to patients,” said Mrowietz, who believes that patient-centered outcomes will be increasingly included in clinical trials for chronic disorders in general, not just those involving cancer or the skin.

A dermatologist who focuses primarily on skin cancer, Paola Pasquali, MD, chief of the Dermatology Service, Pius Hospital de Valls, Valls, Spain, agreed. Citing her own experience, she said that patient-centered care is already widely employed in the field of oncology overall and in dermatologic oncology specifically.

“I think the value of this is common knowledge in cancer treatment,” she told Medscape Medical News. She noted, for example, that partner participation in clinical decisions is standard practice, and patients are encouraged to select therapies based on their own priorities, including ones that may have fewer side effects, but less impact on disease control.

Relative to other areas of medicine, “there has been much more concern about what the patient wants,” she said, acknowledging that optimal care should always include attention to patient well-being.

The POSITIVE study was funded by Almirall Pharmaceuticals. Mrowietz reported a financial relationship with Almirall and with AbbVie, Aditxt, Amgen, Aristea, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Formycon, Immunic, Janssen-Cilag, LEO, Merck, Sharp & Dohme, MetroPharm, Novartis, Phi-Stone, Sanofi-Aventis, UCB, and Union Therapeutics. Pasquali reported no potential conflicts of interest.