P104 Developing the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) to explore natural history and identify endpoints for the rare disease recessive dystrophic epidermolysis bullosa
Authors: Jeffs Eunice , Pillay Elizabeth , Robertson Susan , Wang Yanzhong , Martinez Anna , Mellerio Jemima 
Published: June 2024

Abstract
Epidermolysis bullosa (EB) comprises a collection of rare skin fragility diseases characterized by mucocutaneous wounding from minimal trauma. For recessive dystrophic EB (RDEB), a paucity of detailed knowledge about symptom presentation, severity and progression throughout life, treatment resource use and costs poses a challenge for delivering robust clinical trials and interpreting RDEB findings. The Prospective EB Longitudinal Evaluation Study (PEBLES) was established to explore the natural history of RDEB and identify potential outcome measures for clinical trial use. This prospective longitudinal observational study was designed to collect comprehensive data from a large cohort of patients with RDEB across all ages recruited from two national UK EB reference centres. Data collection at baseline and annually (≥ 10 year olds) or 6-monthly (&lt; 10 year olds) was wide ranging, including clinical features, laboratory parameters, events occurring in the review period (hospital admissions, squamous cell carcinoma), interventions (hand surgery, oesophageal dilatation), severity and quality of life scores, resource use and socioeconomic costs. Reviews were conducted as face-to-face interviews (virtual reviews during the COVID-19 pandemic), and health records (electronic, paper) were explored to update information since the preceding visit. Screening commenced in November 2014, with 71 UK participants recruited over 9 years (54 adult, 17 child recruits). Their subtypes were RDEB-severe (n = 28), RDEB-intermediate (n = 25), RDEB-inversa (n = 11), RDEB-pruriginosa (n = 6) and RDEB-pretibial (n = 1). They provided 427 reviews, median 7 (range 1–16), with 54 (76%) providing ongoing reviews (median 7 years’ participation); six (8%) died and 11 (15%) withdrew. The preliminary findings were reported as oral and poster conference presentations, with subsequent findings prepared for publication, including itch, wound care costs, pain, quality of life, and milestone events. A steering group monitored study conduct and advised on plans to analyse and disseminate the findings, including future use of an approved repository for findings. To ensure the sustainability of PEBLES and to facilitate expansion to new sites, a REDCap database replaced the original bespoke database. Attempts to expand PEBLES in the UK were unsuccessful, but an expansion team facilitated establishment of two new sites (Austria and Germany), with recruitment to commence early 2024. PEBLES has generated a large number of linked reviews, with publications of important findings regarding itch and costs of wound care and further dissemination planned. PEBLES can be expanded to additional sites, which will increase the participant pool and allow comparison of findings from three countries. Study findings will enable clinicians and researchers to better understand RDEB and variations across subtypes and could form a detailed synthetic control for future RDEB trials.