This research is to create a database of information about the progression of RDEB from birth, through diagnosis and into old age, that will be of great value to researchers and RDEB families and support the economic imperative for finding better treatments and a cure for EB.

Prof Jemima Mellerio works in London, UK, collecting information on different subtypes of RDEB by interviewing patients every 6 months (under 10yo) or every year (10yo+) and recording their experiences of itch, pain, sleep and general quality of life. Clinical measurements such as bone density, heart scans and blood test results will also be recorded along with types and costs of dressings used and all the information made available to help families and researchers to better understand what a diagnosis of RDEB is likely to mean. This project is called the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study, abbreviated to PEBLES.

 

Contents:

• Project summary (top of page)
• About our funding
• Final progress summary
• Latest progress summary
• About our researchers
• Why this research is important
• Researcher's abstract
• Researcher's progress update
• Researcher's final progress update

 

About our funding:

Research leader	Prof Jemima Mellerio
Institution	St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and Great Ormond Street Hospital for Children NHS Foundation Trust, London
Type of EB	RDEB
Patient involvement	Yes
Funding amount	£734,790
Project length	9 years
Start date	2013
DEBRA internal ID	Mellerio1

 

Final progress summary:

The PEBLES study has recruited 65 people (16 children and 49 adults) with different subtypes of RDEB since 2014 and carried out over 360 reviews of their symptoms and experiences.

The December 2022 PEBLES participant newsletter is available here.

In 2023 researchers published the findings of their project in a research paper about itch in RDEB. Read an article about the published findings for a general audience here. In 2024, researchers published again, describing the costs of UK community care for people living with RDEB based on information gathered in the PEBLES project.

The PEBLES Team would like to say a big thank you to DEBRA UK for funding the study from 2014-2022!

 

Latest progress summary:

53 people with RDEB are involved in the PEBLES study.

In 2019, the areas of research were listed as:

1. Demographics	11. Iscore EB	21. Mobility
2. Diagnosis	12. Lueven itch score	22. Renal/urology
3. Family history	13. Interventions	23. Investigations
4. Clinical trials	14. Pain	24. Cardiology and anaemia
5. Non-EB medical history	15. GI tract including nutrition	25. Medications
6. Birth history	16. Dental	26. Dressings and care
7. Growth	17. ENT	27. Costs of care and dressings
8. Endocrine (including puberty and bones)	18. Airway	28. Social and employment status
9. Skin	19. Eyes	29. Quality of life
10. BEBS score	20. Hands

2017 update - PEBLES: where are we now?

55 consented patients: 11 children and 44 adults. 2 withdrawn, 1 lost to follow-up
52 completed data for 1st assessment
46 completed 2nd assessment
23 completed 3rd assessment
5 completed 4th assessment
3 completed 5th assessment
1 completed 6th assessment

In 2015, two posters were presented to the British Association of Dermatology summarising results to date:

PEBLES poster BAD 2015

Literature Review BAD 2015

 

About our researchers:

Lead researcher: Prof 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.

Co-researchers: Dr Anna Martinez, Ms Elizabeth Pillay and Ms Eunice Jeffs.

 

Why this research is important:

We have started by looking at the issues that are most important to people living with EB, namely pain, itch and quality of life. This highlights that RDEB has a very profound impact on people’s daily lives across all subtypes of disease and at all ages. We have also started to explore the costs of caring for EB through detailed analysis of costs of dressings and retention garments, as well as the cost of paid care. This information reveals the very high financial impact of RDEB and will, we hope, underscore the economic imperative for finding better treatments and a cure for EB. we are enormously grateful to all those that have agreed to take part in this research project.

Prof Jemima Mellerio

Back to contents

 
Researcher’s abstract:

Grant Title: Natural History and Clinical Endpoints Study in Epidermolysis Bullosa.
PEBLES: Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.

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

The second phase of this project was to develop an electronically based questionnaire to capture data from EB patients, families and carers. Data captured included demographic details, family history, blister count, itch, pain and laboratory parameters such as DEXA scans (measures of bone density), blood tests and echocardiograms (heart analysis) - the tablet can capture up to 2,000 items per patient. This information is anonymised and then uploaded on to a secure server which can then be examined and compared. The data so far have been shown to be robust and have provided a framework to help map the natural history of the disease, along with useful information on types and cost of dressings for example.

 

Researcher’s progress update:

November 2019:

Results from this study presented here include 53 participants with 4 different types of RDEB (41 adults and 12 children):

• 14 adults and 11 children have RDEB-generalised severe (RDEB-GS).
• 18 adults and one child have RDEB-generalised intermediate (RDEB-GI).
• 8 adults have RDEB-inversa (RDEB-INV).
• 1 adult has pruriginosa (DEB-PR).

This update focuses on the findings regarding itch, pain, quality of life, and cost of dressings and associated care.

Pain and EB

So far, participants have been reported to suffer from pain which affects from 1 – 7 nights’ sleep. Background pain has been measured as well as pain levels recorded during dressing changes, confirming that dressing changes do increase pain levels.
Impact of EB on Quality of life (QOL)
Those with RDEB-GS reported the worst QOL and so far have reported significant difficulty with activities such as bathing, showering, shopping and movement outside of the home, unlike the other subtypes who experienced lower impact. All groups reported the need to avoid some sports, although those with RDEB-GS were more likely to avoid all sports.
Children and their parents, like the adults, reported greater impact from EB on physical health and less impact on psychosocial health, including emotional, social and school-related functioning although this was still significant. Parents reported greater impact of EB on quality of life than did their children, highlighting the family wide impact.

Itch and EB

Participants with RDEB-GS reported the greatest frequency of itch, along with severity and distress from their symptoms, but the shortest duration of itching. All RDEB subtypes reported problems with lesions and difficulty falling asleep as a result of itching. Impact of itch on disturbance to routines, loss of appetite, change in behaviour towards others and loss of concentration was also reported by participants with RDEB-GS, again somewhat worse when compared with other subtypes.
It was clear from additional comments provided that many are frustrated by the lack of effective treatment for itch and want new treatments to be developed.

Dressings / care cost of EB

For the 53 recruited patients, the total annual cost of treatment of dressings is conservatively estimated at nearly £3million: this includes at least £2,431,844 for treatment with dressings, tubular bandages and retention garments, and over £377,650 paid care for 13 individuals (10 of whom had RDEB-GS). In addition, 18 unpaid carers were unable to seek employment because of their EB “responsibilities” although the cost of this could not be calculated.
Most participants (71%) changed their dressings all at once, with average dressing change time ranging from 39 minutes per day for RDEB-GI to 105 minutes per day for RDEB-GS.

What next?

The research team plan to look at how itch, quality of life and cost of treatment changes over a 2-4 year period by comparing data from participants with four or more reviews. As they collect more data from each participant, they will be able to look at changes over longer periods of time.
They will then look at other aspects of the data they have already collected, for example, identify the most severe symptoms, more detailed and comprehensive costings for treating EB, and the impact of caring for EB on the lives of participants and their families.
The team also plan to recruit more patients, and particularly more children. They will regularly analyse the data, gradually addressing a wider range of issues and analyses which will provide valuable data on many parameters
The research team presented these findings to other health care professionals at the 2020 EB international conference in London and plan to present and publish data for wider dissemination.

Extension of the project will enable:

1. Ongoing 6-monthly and 12-monthly reviews of existing participants, 52 (95%) of whom remain in the study.
2. Continued recruitment of additional patients from the London centres, with a priority for recruitment of children, to capture more about the onset of EB.
3. Ongoing analysis of available data, widening the parameters and including data from existing and additional reviews.
4. Publication of findings in journal/s and at conferences –specifically pain and itch data from the PEBLES database as these are important symptoms for patients.
5. Publication of the methodology of PEBLES so similar studies for other forms of EB and potentially other conditions can follow the process and key learnings from this work.
6. Integrity of the data through purchase of data management support to ensure data are error free prior to statistical review.
7. Forming of a steering group to help prioritise the data for analysis. This large amount of data will take 2 years to analyse, therefore prioritisation is important (anticipated to be quality of life, cost of dressings, paid care and nutrition).
8. Exploration of the feasibility of extending PEBLES to specialist EB centres in other sites and additional countries.

In Summary

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

 

Back to contents

 

Researcher's final progress update:

The aim of PEBLES has been to explore, in detail, the natural history of all forms of recessive dystrophic epidermolysis bullosa (RDEB), to quantify and follow how the condition presents, how it changes over time, the complications and problems that can occur, symptoms and quality of life, and the socioeconomic costs of living with RDEB.

To do this, the PEBLES team have recruited children and adults with different types of RDEB that attend the EB services in London (Great Ormond Street Hospital (children) or Guy’s and St Thomas’ Hospital (adults)). They have collected detailed information on many different aspects including diagnosis, details of the physical problems relating to EB and other health problems throughout life, medical procedures, medications, hospital appointments, disease severity scores, subjective measures such as pain, itch and quality of life, results of laboratory tests and the costs of dressings and care.

After an initial review, the PEBLES team repeat reviews every 6 months (in children up to 10 years) or annually (over 10-year olds). Over time, this builds a picture of different subtypes of RDEB in individuals of different ages, but also how it progresses over time in any one individual. Previous studies have failed to collect such detailed information and have rarely broken down the findings by RDEB subtype, which is important as different forms of RDEB can vary a great deal in terms of severity, complications, symptoms and impact on day-to-day living.

The information from PEBLES will help to identify outcomes that are important and significant in different types of RDEB, acting as control data for future clinical trials. When new therapies are developed for people living with RDEB, PEBLES data will be able to demonstrate how the condition would normally behave, serving as a comparator for data collected in trials where interventions aim to alter the disease course.

In addition, information collected in the course of the study will help build up a comprehensive picture of how different types of RDEB change over time, from birth throughout all stages of life. This information will help inform people living with EB, their families and medical teams about the prognosis of disease, what they can expect over time and likely complications that might need monitoring or treatment. Further, PEBLES data on the detailed socioeconomic costs of caring for people with RDEB will be extremely valuable in substantiating investment into the design and delivery of new therapies for EB.

PEBLES has been recruiting participants since late 2014 and had carried out over 360 reviews from 65 recruits by early September 2022. Since RDEB is a rare disease, particularly when broken down into its different subtypes, and with individuals of all ages being included, we have tried to comprise as many participants and as many reviews in the same people over time as possible to build a full and accurate picture of the condition.

Data from PEBLES will be published and available to researchers undertaking clinical trials with a wide range of different approaches e.g. cell or gene therapy, gene editing, protein replacement therapy and drug therapy. They will be able to use information from the study to help select appropriate and reliable outcome measures for their clinical trials. In addition, researchers may be able to use PEBLES data as surrogate control data for their studies; this could be particularly helpful because RDEB is so rare and it may not always be possible or ethical to have sufficient individuals taking placebo treatments in a trial.

Once information from different areas have been published, the PEBLES team will make anonymised raw data available in a repository for researchers or pharma companies to access with the team’s permission. This will mean that they can see the information in more detail to get more information about outcomes or control data. In this way, PEBLES will be available to support the wider clinical research community to help deliver new therapies to people with EB. (From Final Report January 2023.)

 

Back to contents