Best systemic treatments for adults with atopic eczema over the long term (BEACON)

Research question: What is the most effective, tolerable and cost-effective systemic therapy to treat moderate-severe adult atopic eczema? Background: Atopic eczema (eczema) is the most common inflammatory adult skin disease. It presents with itchy, sore, inflamed skin that leads to scratching, infection and sleep loss along with significant psychological and social impairment. Moderate to severe disease (around 10% of the eczema population) usually requires systemic therapy with commonly used treatments including ciclosporin (the only licensed standard therapy), methotrexate and dupilumab (a novel, targeted therapy). There is clinical equipoise as to which intervention is best, and no active comparator data for dupilumab. Aims and objectives: To determine the effectiveness, tolerability and cost-effectiveness of dupilumab and methotrexate compared with ciclosporin in adults with moderate to severe eczema; to identify the optimal treatment pathway over one year; to use a platform design to enable future, additional comparator arms. Methods: This is an assessor-blind, randomised controlled trial. Adults with at least moderate disease will receive dupilumab (subcutaneous), methotrexate (subcutaneous) or ciclosporin (oral) randomised 1:1:1. The primary outcome (blinded) will be objective disease severity at 6 months using the core outcome measure of Eczema Area and Severity Index (EASI); secondary endpoints relate to symptoms (itch, disease control), quality of life, depression, anxiety, safety and cost effectiveness. Participants will be assessed at months 0, 1, 3 and 6 with an optional dose increase at month 3. At 6 months, treatment will be continued for a further 6 months if defined effectiveness criteria are met, or switched to an alternative therapy in line with NICE guidance (dupilumab to methotrexate, ciclosporin/methotrexate to dupilumab). The sample size of 402 gives 90% power to detect a mean absolute difference of 6.6 (minimal clinically important difference (MCID)) in EASI (superiority for methotrexate or dupilumab against ciclosporin; if treatment benefit is demonstrated for both, methotrexate will be compared against dupilumab). Q learning methods will be used in a secondary analysis to identify the pathway that optimises outcomes at 12 months. Timelines: Forty eight months to deliver this project is realistic given the experience and track record of the research team, established network of recruiting centres, and requisite infrastructure and operational support through the Clinical Trials Unit at Kings, NIHR Clinical Research Network and UK Dermatology Clinical Trials Network. Impact: This trial will provide the first comprehensive head to head evidence on the comparative effectiveness, tolerability and cost effectiveness of the three key systemic agents used to treat moderate-severe adult eczema, and the optimal 12 month treatment pathway. These data will translate into improved health outcomes, minimise treatment switching, and enable healthcare commissioning based on clinical evidence and value for money. Partnership with the National Eczema Society and input from patients means that our findings are relevant to patients’ needs. This trial will be set up to facilitate future transition into a multi-arm multi-stage platform trial that can evaluate new biologic and oral therapies for eczema.