Our research Current projects PEBLES symptom study Professor Jemima Mellerio works in London, UK to collect information on different types of Epidermolysis Bullosa by interviewing patients every 6 months (under 12yo) or every year (13yo+) and recording their experiences of itch, pain, sleep and general quality of life with EB. 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 with EB and EB researchers to better understand what a diagnosis of EB is likely to mean. This work is named PEBLES for Prospective Epidermolysis Bullosa Longitudinal Evaluation Study. Contents: Project information Abstract Grant Title: Natural History and Clinical Endpoints Study in Epidermolysis Bullosa Also known as PEBLES: Prospective Epidermolysis Bullosa Longitudinal Evaluation Study Investigators: Jemima Mellerio and team (extending out to include Birmingham as well as Guy’s and St.Thomas’/Great Ormond Street Hospital) Co-investigators: Dr Anna Martinez, Ms Elizabeth Pillay & Ms Eunice Jeffs 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. Start Date: 01/07/2013 Grant Total: £734,790 Current grant extension funding: £321,906 Research type: Continuation and expansion of the ongoing project to document the natural history of EB and prospective data Abstract 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. Facts about this research Project 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. What is important about this research? “It has been exciting to start to interrogate the data that we have been collecting through the PEBLES project over the last 5 years. 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 now starting to look at data relating to other aspects of EB including bone health and gastrointestinal aspects. DEBRA’s ongoing support of PEBLES means that we will be able to recruit further individuals with RDEB as well as to collect more ongoing data in those already in the project. The strength of the data relies on having a good number of recruits; we are enormously grateful to all those that have agreed to take part in this research project.” Professor Jemima Mellerio 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.