A pan-European register-based observational study of abrocitinib and conventional systemic therapies in moderate and severe atopic dermatitis: the DREAM TO TREAT AD study protocol.

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin condition. Currently, there is a lack of real-world evidence regarding the effectiveness of systemic therapies for moderate-to-severe AD. Abrocitinib is a novel Janus kinase 1 selective inhibitor licensed for AD in adults and adolescents requiring systemic treatment. The DREAM TO TREAT AD (D2T AD) study was set up to collect real-world data on abrocitinib and conventional systemic treatment use in moderate-to-severe AD. It aims to describe treatment patterns and effectiveness within a 3-year follow-up period in five registers: Ireland [Atopic Eczema Systemic Therapy Register (A-STAR) Ireland], Denmark (SCRATCH), Germany (TREATgermany), the Netherlands and Belgium (TREAT NL/BE), and the UK (A-STAR UK).

Methods: The study protocol and methodology were developed collaboratively by academics of the participating registers with the study funder. The study follow-up timepoints and outcomes are based on an international Delphi exercise previously run by the TREAT Registry Taskforce. All five registers collect data in several domains, including patients' characteristics and treatment outcomes in patients receiving systemic treatment. Assignment to treatment was decided by the treating clinician. Data collected by the registers will be transformed into harmonized datasets and then to analytical datasets (ADS) to address research questions. Study objectives include describing patient baseline characteristics, in addition to clinician- (Eczema Area and Severity Index) and patient-reported outcomes [Patient-Reported Eczema Measure (POEM), Children's/Dermatology Life Quality Index (C/DLQI), Peak Pruritus Numeric Rate Scale (PP-NRS)] at baseline and follow-up, as well as treatment patterns while on abrocitinib and conventional systemic treatments. The ADS will be analysed using the novel DataSHIELD solution that enables centralized statistical analysis on decentralized data (i.e. without data leaving the register of origin). The DataSHIELD solution includes central analytic hubs (CAHs) and local data nodes (LDNs). CAH can remotely interrogate LDNs via an internet connection using analytical commands. Each LDN produces local statistical results that are sent back to the CAH, which can then combine the results from all LNDs without seeing any patient-level data.

Discussion: D2T AD undertakes a novel federated data analysis approach across five registers in observational dermatology research and will provide crucial information on AD treatment outcomes for clinical decision-making, in addition to proving the feasibility of this type of scientific collaboration.

Protocol Registration: EMA RWD Catalogue (EU PAS no.: 108468; study ID: 199009; https://catalogues.ema.europa.eu/node/3894/administrative-details).