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Natural History and Clinical Endpoints Study in Epidermolysis Bullosa

Natural History and Clinical Endpoints Study in Epidermolysis Bullosa

Investigator: Professor Jemima Mellerio, Consultant Dermatologist

Co-applicants: Dr Anna Martinez, Mrs Elizabeth Pillay

Institution: St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital and Great Ormond Street Hospital, London.

Total Grant Funding to date 2018: £260,748 since 2013  

New Extension funding until 2019 - £152,136

Facts about this research:

  • This project is also known as PEBLES which is an acronym for Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.
  • It’s important because clinical trials of new treatments for RDEB need endpoints – so we need to know about the natural history of the disease in order to know what to measure.
  • So far 55 patients have consented to participate – 44 adults and 11 children.
  • Each participant (or participant’s parent) receives a booklet of questionnaires to complete before review by a researcher as well as a camera to collect a standard set of photographs.
  • Examples of data collected consist of basic background data, laboratory, clinical information such as, blister count, age appropriate measures of items such as quality of life (collected from questionnaires), levels of pain and types and number of dressings used.
  • This provides a comprehensive picture of all aspects of RDEB patients from birth into childhood and beyond, information that has never been collected before or in such detail.
  • It will be extended to other EB centres.
  • It may also extend to collecting information on other types of EB.

Lay summary

Aims & Objectives

This study was initially funded in 2013 to help identify and define relevant endpoints which could be “measurable” target outcomes for clinical trials. A systematic review was initially carried out of all the current research in order to determine what knowledge there is about the natural history of RDEB. This highlighted that there was a necessity for a prospective longitudinal study that included assessment of laboratory, clinical, quality of life and socioeconomic information to understand the disease progression to a greater extent.

The second phase of this project was to then develop an electronic based questionnaire to capture many aspects of data from EB Patients, families and carers that has never been collected before.

Detailed background and clinical data being collected includes the following:

  • Demographic details, such as gender, date of birth, family history, ethnicity, school or work and social history (including type of EB and type of mutation).
  • Growth and development are also included as useful information such as height, weight, body mass index and onset of puberty.
  • Neurological and Musculoskeletal Health – Such as range of mobility, whether fully mobile to limited walking or use of wheelchair.
  • Hand contractures and splints and previous surgery.
  • Health of eyes, ears, nose and throat and any symptoms or interventions.
  • Health of the gastrointestinal tract and information about nutrition, oral/tube feeding, problems with swallowing, bowel habit or colitis.
  • Dental Health – Microstomia, caries or missing teeth and surgery.
  • Blister count, itch, pain and laboratory parameters such as DEXA scans (which measure bone density), blood tests and echocardiograms, information from questionnaires and scores that measure severity for pain, itch and quality of life.
  • Information about cancer such as age of first squamous cell carcinoma, number of sites, therapies and other types of cancers.
  • Blood ferritin and iron levels, kidney function and inflammatory levels are recorded.
  • Health economic data is also captured including hospital appointments, admissions, length of stay and medication, dressings, (types, amount, sizes, cost), number of dressing changes and who undertakes them.
  • Standard views of skin are photographed on tablet or patient’s own camera.

Recruitment to PEBLES started in November 2014. To date this project has recruited 55 patients with different types of recessive dystrophic EB (RDEB) into the study, and gathered prospective data in the majority of these individuals (every 6 months for up to 10 years old, and annually thereafter). 

  • So far 55 patients have consented to participate – 44 adults and 11 children. Of these 55 patients, 2 patients have withdrawn and 1 patient has been lost to follow up.

GS – Generalised Severe      GI – Generalised Intermediate     I – Inversa       Pru - Pruriginosa

The tablet is able to capture up to 2,000 possible data entry points per patient. The information recorded is anonymised and then uploaded on to a secure server so it can be examined and compared. Further funding of the project will enable further data collection from patients who are already part of the project as well as recruitment of additional patients from the London EB centres as well as extending it to the Birmingham paediatric and adult EB services, (Birmingham Children’s Hospital and Solihull Hospital in addition to Ormond Street and Guy’s and St Thomas’).

Part of the extension funding for this project will also include the transfer of existing and prospective data to a new web-based system, allowing the data to be centralized and analysed in greater depth. This will help facilitate data retrieval and will form the basis of an initial review of pain and itch in individuals with RDEB from more patients and hopefully from a second UK site as the new system will be able to handle more data. Early results have provided information on the costs of managing EB and most importantly a framework to help map the natural history of the disease. An example of these early results show that the range of costs for dressings, per patient, per year, range from £92.64 to £542,543.04.

In Summary

PEBLES will provide more detailed information about RDEB than previously collected. It will help build a comprehensive picture of all aspects of well-characterised RDEB patients that will also extend to other centres and in time, for other types of EB. Ultimately, this project will help identify meaningful endpoints that will inform future clinical trials that are needed for all types of EB.

What is important about this research?

“The extension of this DEBRA funded research means that we can open the study to the two Birmingham EB centres and increase the numbers of individuals with recessive dystrophic EB that we can recruit.  Doing this is essential as the strength of the project lies in capturing as much detailed information from people with different types of RDEB at all ages so we are better placed to follow the natural history of the disease. Only by doing this can we start to look at meaningful end points that will be relevant to future clinical trials for EB. ”

Investigator Biography


Professor Jemima Mellerio is a Consultant Dermatologist and professor at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust. She has over 20 years working clinically in the field of EB and other genetic skin diseases, as well as a research background looking at the molecular basis of different types of EB, and clinical trials into newer therapies for EB such as fibroblast and mesenchymal stromal cell therapy. She is dedicated to continuing this work to develop more effective treatments for all types of EB.


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