Abstract
INTRODUCTION: Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin and mucosal fragility, leading to painful blisters and erosions. Among its subtypes, the severe form of EB simplex (EBS-sev, OMIM 131760) is associated with widespread blistering from birth, mucosal involvement and increased neonatal mortality due to infections. EBS is primarily caused by dominant mutations in the KRT5 or KRT14 genes.There is currently no curative treatment for EBS; management is symptomatic and multidisciplinary. Our recent data indicate that EBS-sev is associated with an inflammatory profile involving elevated levels of Th17-polarising cytokines (TGF-β, IL-6, IL-21), suggesting a role for the Th17 immune response in disease pathogenesis. METHODS AND ANALYSIS: EBULO is an open-label, multicentre phase 2 study, over a 20-week period, to evaluate the oral daily intake of apremilast (dosage depending on the age and the weight of patients) based on a challenge/dechallenge/rechallenge design. Patients are evaluated during five on-site visits, and apremilast is administered for 16 weeks during two treatment periods, with a 4-week treatment interruption in between. The primary outcome will be to assess the efficacy of apremilast in the treatment of patients with EBS-sev evaluated by counting the number of new blisters, a method specifically developed for this protocol to overcome the lack of reliable assessment tools in EBS-sev. The secondary outcome will include assessing the safety and tolerability of apremilast treatment through the description of the specific events occurring during the treatment periods of the study. ETHICS AND DISSEMINATION: The French Ethical Review Authority has approved the EBULO trial protocol. Results will be published in international peer-reviewed journals and summaries will be provided to funders and participants of the trial. TRIAL REGISTRATION NUMBER: NCT06509984.