Title: Maintaining skin remission using treat-to-target – changing paradigms in psoriasis care
Funder: Department of Health and Social Care

Abstract: Background Psoriasis is a common, debilitating skin disease that costs the NHS >750 million/year, largely because management has been transformed by powerful biologics costing >10,000/year/patient. Routine use of biologics has enabled more patients to achieve clear skin ('remission') than ever before. While trial data indicates remission can be maintained with less frequent dosing or stopping treatment, individuals in remission currently continue biologics indefinitely in routine practice. This is burdensome to patients, healthcare services, society, and the economy. 'Treat-to-target' involves modifying treatments to reach/sustain a pre-defined goal. It has proved successful in chronic diseases (hypertension, diabetes, rheumatoid arthritis) with close monitoring. A treat-to-target strategy for psoriasis, whereby individuals receive biologic doses as required to maintain remission, promises lower infection and adverse event risks, injection burden and cost compared with continuous treatment. Individuals in remission on newer generation biologics such as IL-23p19 inhibitors are particularly suited to treat-to-target since these agents are highly effective with low/absent immunogenicity. However, this strategy is yet to be assessed in real-world practice. Hypothesis/Aim I hypothesise that a biologic treat-to-target strategy for remission, which is remotely monitored using patient-generated health data, has non-inferior clinical-effectiveness and superior cost-effectiveness over treatment continuation in psoriasis. This research seeks to develop and determine the feasibility of this strategy for routine care. I will identify and address implementation issues before it is rolled-out in a definitive RCT for effectiveness evaluation. Methods A three-phase programme of mixed methods research is planned. In Phase 1, I will refine our existing web-based REDCap platform (PsoProtectMe, www.psoprotectme.org, >4,500 participants) for use as a remote monitoring tool. I will identify the barriers and enablers to treat-to-target and remote monitoring (including in under-served groups) using a multi-stakeholder participatory co-design study. Focus groups involving patients, clinicians, NHS managers will inform iterative refinement of PsoProtectMe. A final patient workshop will beta-test the optimised platform. The co-creation design will ensure the platform is sensitive to end-users' needs whilst being implementable and sustainable within the NHS. In Phase 2, I will assess the usability of, and engagement with, the remote monitoring tool over 12-months. A prospective longitudinal cohort study in patients with psoriasis will assess the utility of remotely monitoring self-reported outcomes and self-taken photographs over time. Semi-structured interviews with a subset of participants will explore the acceptability of regular self-reporting. In Phase 3, I will implement a remotely monitored treat-to-target strategy, comprising withdrawal of treatment in individuals with clear skin for >1 year on highly-effective IL-23p19 inhibitors (stable remission), followed by re-treatment at the first sign of recurrence. A 12-month multicentre feasibility randomised-controlled trial will determine the practicality and acceptability of real-world delivery for patients and clinicians.Impact/Dissemination This research will deliver a step-change in treatment paradigms for the increasing number of psoriasis patients in remission on biologics. It promises personalised patient-driven treat-to-target care, reduced long-term drug-related morbidity and cost savings for the NHS. It is generalisable to other immune-mediated conditions treated with biologics. Findings will be disseminated to clinicians/patients/public/industry/policy makers, ensuring immediate clinical relevance, and facilitating translation to patient benefit.

Lay abstract: Personalised 'as required' treatment - new concepts for maintaining clear skin in psoriasis BackgroundPsoriasis is a common, debilitating skin disease that affects between 2 and 4 in every 100 people worldwide. Scientific research has delivered increasingly powerful injection drugs called biologics. More than half of patients receiving newer biologics achieve remission (i.e. clear skin) within a year. Patients currently continue biologics lifelong at standard doses, even when their skin is completely clear. This is burdensome due to regular injections, blood tests, risks of infections and side effects. It is also expensive since biologics cost the NHS ~10,000/year/patient. We know from clinical trials that some patients may be able to stop treatment for a while, and then restart if/when their psoriasis returns. If people only take a drug when they need it this would reduce risks and burden to patients and save the NHS money. Aim I aim to understand whether patients can take biologic treatments 'as required' in routine care whilst still maintaining complete control of their psoriasis (remission). MethodsIn 2020, I led the launch of a secure web-based platform called PsoProtectMe (housed on REDCap at King's College London, www.psoprotectme.org) to monitor the health and wellbeing of people with psoriasis in the pandemic. Over 4500 individuals worldwide (2200 UK) have self-reported using PsoProtectMe. In Phase 1, I will refine PsoProtectMe for remote monitoring of patients who are taking 'as required' treatment. I will use focus groups and workshops involving a diverse range of patients, healthcare professionals and NHS managers to understand the barriers and enablers to remote monitoring and taking 'as required' treatment. This information will be used to refine the remote monitoring platform so it is accessible and sensitive to the needs of users. In Phase 2, I will evaluate how people with psoriasis feel when remotely providing their health data and the practicalities of regularly using the platform. Individuals with psoriasis will be recruited UK-wide using the networks of the Psoriasis Association (UK's leading charity and member organisation for individuals with psoriasis). Participants will submit regular validated measures of their health and wellbeing, and self-taken photographs of their skin, over 12-months. Four-monthly interviews with a subset will explore the acceptability of, and barriers to, regular self-reporting. In Phase 3, I will implement 'as required' biologic treatment, supported by remote monitoring using the refined platform, in the care of patients who are in remission. I will conduct a feasibility trial involving patients from 3 UK dermatology centres. This will determine whether remotely monitored 'as required' biologic treatment is acceptable for patients and doctors, and practical for routine care. I will ultimately aim to assess in a larger study whether it will lead to cost savings and similar quality-of-life and rates of clearance of psoriasis, compared with continuous treatment, and offer it across the NHS. Patient/public involvementI developed this research in collaboration with the Psoriasis Association and will continue to work with them throughout. I sought patient/public involvement (PPI) through patient/public advisory group meetings and national scoping surveys. Our patient and lay members group will meet six-monthly, appraise participant resources, advise on PPI strategy and feedback on findings. Dissemination/Impact I will disseminate results to all stakeholders through national/international conferences, research papers and by working with our professional and patient community. This research promises to transform and streamline clinical care, with personalised treatment provided according to need. I will highlight this work to other medical specialties prescribing biologics. It will thus help wide-ranging patients with immune-mediated diseases to reduce a lifelong burden of medications, maintain better control of their health, and save money and resources for the NHS.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM