Dupilumab step-down strategy to maintain remission in adult and adolescent patients with atopic dermatitis: study protocol for a non-inferiority randomized trial (MADULO)

Background Atopic dermatitis (AD) is a prevalent chronic relapsing inflammatory skin disease affecting individuals across the lifespan from childhood through adulthood. The burden of AD is now well recognized. Recent advancements in understanding its pathophysiology have led to significant therapeutic improvements over the past five years. Dupilumab stands as one of the pioneering systemic treatments available for AD. While dupilumab enables rapid and substantial short-term disease control, assessing the effectiveness of long-term therapeutic strategies is crucial. Improving knowledge on the management of maintenance treatment is a key clinical question for patients and clinicians. We hypothesize that spacing dupilumab injections in adolescent and adult patients with controlled AD is an interesting maintenance treatment option. This randomized clinical trial aims to compare a step-down strategy involving spaced dupilumab injections with standard maintenance treatment in patients with controlled AD. Methods This multicentre non-inferiority randomized controlled trial will enroll 256 adolescents and adults with controlled AD treated with labelled dose of dupilumab during at least 12 month from thirty-one academic hospitals. Participants will be randomly assigned in a 1:1 ratio to either the experimental group (progressive step-down injection strategy) or the control group (standard maintenance treatment, i.e. 300 mg dose administered every two weeks, for adolescents over the age of 12, the dose is adjusted according to weight). The primary outcome measure will be the Area under the Curve of the Atopic Dermatitis Control Tool score recorded weekly over one year. Discussion In clinical practice, AD patients who respond favorably to dupilumab often express interest in reducing treatment frequency, sometimes on their own inititative. Anticipated benefits of a step-down strategy include potentially improved long-term risk-benefit profiles and enhanced patient quality of life through reduced injection frequency. Collectively, this approach may yield insights into optimal long-term dupilumab strategies for responders while potentially lowering systemic treatment costs for healthcare providers. Trial registration Clinical trial.gov: NCT05642208 first published on 8 December 2022 (https://clinicaltrials.gov/study/NCT05642208?term=MADULO&rank=1) ; Clinical Trials Information System, EUCT number: 2022-501179-23-00 first published on 8 November 2022 (https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2022-501179-23-00).