In the second half of the pre-recorded session and interviews at EADV 2023, Professor Christine Bodemer (Paris Descartes – Paris Sorbonne University, France) and Dr Mauricio Torres (Fundación Universitaria de Ciencias de la Salud, Columbia) discuss real-world experience with birch bark extract and patient communication in clinical practice.
Biggest challenges for people living with EB – Impact of treatment on total body surface area
We have to keep in mind that EB is a genetic disease occurring, in the majority of cases and worse with a chronicity. And so at the beginning it's a very, very difficult disease to be appreciated by the parents of the children because they have to understand the chronicity of the mucosal cutaneous wounds and their consequence. And it's like a tsunami. And as there is no sufficient number of trained caregivers they have to become the caregivers of their own child. And so it impacts the quality of life of the patient and also of the whole family.
And what wants the families and the patient? They want to be able to have a real life with EB and not only to survive, and for that to have time in us to live. And so it's very important to try to have a better, to reduce the delay of the daily dressing change for the care of EB wounds. It's very important. And also to reduce the distress at this period because the pain can be very important. And so to have to stimulate a better wound healing in a shorter time. And so to reduce pain, to reduce infectious complications and to permit to have more time for the daily life. And the burden of the patient and his family is very important because it's not only a physical burden, of course, but also a psychological burden, a social burden with difficulty of social integration, and an economic burden because of the cost for the management of the disease. And so if we are able to reduce the time for the wound healing and to reduce the number of wounds and the severity of the wounds, it permits to have a better quality of life. After the easy study, the blind double study phase, there was an open levels phase. And during this open level phase, we observed, after 24 months, we observed that there is a decrease of the body surface percentage involved. And so it means that it's possible also, with the application, the daily application of the produce to finally decrease the involved body surface areas. And so it's very important for the patients who are responders to the project.
Professor Bodemer started the second half of the session discussing quality of life for people with epidermolysis bullosa (EB), results of the EASE study and real-world experience with birch bark extract. EASE was a double-blind, randomised phase 3 trial investigating birch bark extract (development name, Oleogel-S10) in people with dystrophic EB (DEB) and junctional EB (JEB)11 . In the study, 41.3% of people had first complete target wound closure within 45 days with birch bark extract, compared with 28.9% with control gel11 . Adverse events were observed with similar frequency in both groups11 .
Professor Bodemer considers the daily priorities for people living with EB and what the results of the EASE study could mean for them. She also discusses key takeaways from her centre’s experience in France.
Experience from centre in France – Experience in the clinic and hopes for the future
In my centre, we have a large series of patients with EB, not only early EB patients, but other forms of EB. And really, we are happy to propose birch bark extract to try to improve the patients. And we try to explain the patient that it's not sure that we will have an improvement, but we're sure that the product is safe, now, without a worsening of infectious complications, for instance, of the wounds. And so we propose, systematically, to try the product and we explain also, it's very important, we explain that it's not a definitive treatment. It means that it doesn't cure the treatment. So the wounds and the disease. And it's very important to explain that at the beginning. If we don't do that, of course, it's not, the patients are not so happy.
But by this way, the patients understand, the parents, the families, understand and they're very happy to have these new products. And I highly think that in the future, we will have several different products and it will be the combination, the association of different products that could help the patients during their daily life. Of course, what we want is to cure the disease, but we know that it's not yet the possibility. And so it's a real progress to have several approach included the approach with the birch bark extract. I think that it'll be important to know also the experience of the other centres with the use of the products during several months and years in the future. And this experience will be fine. And I really would like, hope, that in the future, it will be possible to have some, perhaps, biomarkers or things like that, very helpful to define which patient is supposed to be really improve with this product or not. And so in the future, I really think that it'll be important to have very large cohort of patients with analyse of biomarkers and to have a better understanding of all the patients, also of the individual patients. Because we don't finally, we don't try to cure a disease. We try to cure a patient with a disease and it's not exactly the same because for the expressions for the phenotype of a disease, it's not only the genes, the mutations, and what we know about a disease, which is important. It's also all the other factors are very important in the daily life of a patient. So if we can, in the future, to have an individual approach of each patient for the combination of the treatment, it will be great.
Professor Bodemer presents the highlights from her pre-recorded presentation of the session at EADV 2023.
The impact of EB – Priorities for people with EB – EASE study efficacy results – EASE study safety results – Priorities for people with EB and the EASE study – Real-world experience in France – From clinical trial to real-world experience
I'm going to discuss on translating clinical data into clinical practise. So, just to keep in mind, epidermolysis bullosa is a very, very devastating and painful disease, And in all the forms of EB you can have a very high pain and high risk of complication, undernutrition, infections and so on. And even in the more severe form as the development of squamous cell carcinoma. And so there is an important deterioration of quality of life with a great difficulty of social integration of the patients. And the impact of EB on patient have been well studied and published in the literature. And as you can observe on this slide, the burden observed in patients with early EB recessive dystrophic forms of EB, it mean with an involvement of collagen VII in the skin. And you can observe that the impact of the quality of life is particularly important because it's the most important impact observed in all these chronic diseases before even dermatomyositis, eczema, psoriasis and so on. And the parameters which impact patients' quality of life in EB is mostly wounds, and frequently non-healing wounds in patients, pain and itch. And so the priorities for people with EB for patients and their family is to try to accelerate wound healing and is certainly the top of the five priority.
But also to reduce the number and severity of EB wounds and also to reduce pain and itch, which are often the most burdensome element of EB and to reduce the distress and time associated with dressing change. And it's very particular moment in the life of the patients with a great anxiety for this moment. And also to reduce the risk of infection of patients and also their caregivers. And it's essential because infectious complication can be even life threatening, particularly in children. And so, this study have tried to evaluate efficiency of treatments in the EASE treatments with the use of oleogel and the use of oleogel in patients with different forms of EB and with protocols that has been set up in 49 sites from 26 countries. And as you can see on this slide, EASE study has been realised with the use of oleogel and the use of also control gel in double-blind study. And it has been possible to observe that there was a higher proportion of patients with targeted wound closure with oleogel when we compare versus control gel at day 45 with a significant difference between the two groups. There were a higher proportion of patients with targeted wound closures in patient with RDEB with the so specific forms, which is one of the most severe forms of EB when we compare to control gel group as you can see on this slide. And so in 72% of patients there is an increase in the probability of target wound closure in RDEB patient with oleogel-S10. Oleogel-S10 provides also sustained produced wound burden and it has been well demonstrated in this study in all patient with oleogel we could observe a great difference between the group with patients treated with oleogel and the patient treated with the control gel we consider the change in BSAP from the zero. Wound complication, if we consider the group with oleogel, you can observe that in all patients with oleogel there was wound complication observe in 61.5% of patients compared to control gel. And during the open label phase study, it was 39.5%.
And if we consider pyrexia, wound infections, pruritus and anaemia, there was no really difference between the two groups. And we can say that in the group with oleogel, so there was probably less side effects observed as we compare the complication observed in the patient with the control gel. And all these complications are certainly related to the disease and to the characteristic of the EB wounds, non-healing EB wounds in patients. And so, the priorities for people with EB are met by the EASE study. With accelerating wound healing as we have just detailed that. And also with the reduction of the pain, even the itch, more study are certainly necessary to have a better evaluation of the action on the itch and also with reduction of the distress of the patient and their families. Because a reduction of the pain and the reduction of the risk of infections, it means no more infections into patients with oleogel and even a reduction of this risk and reduction of the number and severity of EB wounds. So in France we can use with compassionate We can have a compassionate use of oleogel in France and the patients that have been on hold and recruited in the protocols and with a great improvement for the wound healing wanted to continue with oleogel. And so now we have 40 patients with EB diagnosis, well confirmed diagnosis that have received oleogel with compassionate use. The result are as follows; wounds were considered improved in 11 amongst 18 patient with recent wounds improved. And in six among these 80 patients with recent and all wounds improved. And finally, we can say that 20 patients have responded to the questionnaires mentioning that they were very happy to use oleogel. It means that in more than 60% of this 33 patients, we can consider that there is an improvement with the use of oleogel. So, what can we say? We can say that from clinical trial to the experience of the clinicians, we can say that there is certainly an improvement of the wound closure and wound healing with the use of oleogel and oleogel provides a complex and accelerated wound healing in statistically significant progression of EB patients. And that also there is a reduction in clinical study of the global skin involvement of the patients with large wounds on the majority of the skin. And also we can see that there is also an improvement of itch in both clinical study and during the AAC programmes with some improvement, even if statistically it's not perhaps completely proved, but we know how complex are the component of itch in patients with EB and there was an improvement of pain and there is an improvement of pain in patient we use currently oleogel in the compassionate study in France. And also there is probably reduction of the burden of the patient and their family during the dressing change with the use of oleogel.
An open dialogue regarding wound care routine – Potential impact of birch bark extract
My advice is try to know your patient. Definitely, even though we have the proper diagnosis, even though we have the best practise at that moment, if you want to introduce a new routine, a new product on each patient and their families, you need to have a conversation just before the treatment and explaining to them the necessities, the possible outcomes. During the treatment, if there is something you have to organise, something you have to optimise for each of them, and then on the long term, you want to keep the adherence to the treatments, and so I think it's important to follow up every time, asking how they use the product, how do they want to use it, and they can teach us a lot. So know your patient, hear your patient and their family. That's my advice. I think when you notice that your wounds are closing really faster than they used to, that you can control the wounds easily than you're doing before, that's a very important impact on the quality of life, not only for the patient, also for the caregivers of the patient.
This ability of reduction of pain, itchiness, the ability to go to school or go to work without this new blistering or new wounds. What I see the difference is not the age of the patient, it's how chronic or recurring are the wounds. In my experience, the recurring wounds healing process with the [indistinct] is fast, it's really amazing. With the chronic wounds, especially these very long term ones, I'm not that sure of the big impact. The impact that I saw it the most is in recurrent wounds, no matter the age. Obviously, if you're younger, your cells are newer and you can grow fast tissue, but it depends on the chronicity of the wounds.
Dr Torres concluded the session by discussing how to really understand your patient, communication for the best chance at success, and real-world data using birch bark extract in practice. In his centre in Colombia, use of birch bark extract on EB wounds resulted in reductions in body surface area percentage (BSAP) that were consistent with the 2-year results of the EASE study12,13 .
Dr Torres gives advice on how to have an open dialogue with people with EB or their caregivers, for their wound care routine. He describes the potential impact of birch bark extract on quality of life and how clinicians can educate themselves and their patients on new treatments for EB.
Advising patients starting birch bark extract – Education on new EB treatments
Well, it's I think it's important just to introduce a new treatment, a new routine, but also just remember to always have the proper bandages. My opinion, it's works much better if you have the proper dressings and the proper routine of wound care. So keep in mind to not only have the product, also the bandages, and prepare the wound. It's always important just to be ready every time there's a cure dressing. First, know your social or your local association for patients. Usually they are very well trained and they have the latest news. Debra Columbia as an example, but they were all over Latin America and almost all over the world. You can find some information in the EB clinic. They were international. They're always updating, well, and go to meetings. No, and you just, there's a lot of information. There is a lot going on all over the world, so just try to look for it. If you are a healthcare professional, just keep in mind these patients and their family has a lot of doubts, they have a lot of questions. Try to be positive, try to be honest, to give the answers. If you don't have it, just don't feel ashamed, don't feel embarrassed to don't have it. Just look for the proper answers. It's, we have to try to do our best, and I was saying before, the teamwork is necessary in this disease.
Dr Torres presents the highlights from his pre-recorded presentation of the session at EADV 2023.
Introduction – Know your patient – Documenting wound types and duration – Using birch bark extract in practice – Results from real-world experience
When we're seeing, when we're thinking about implications for change, we have to remind that in a world characterised by constant evolution. A need for a change is an ever present reality. We are currently living in a new area for EB, just not only in the diagnosis, classification, also for treatment and management. I think it's an opportunity and also a challenge that involve us, not only as physicians, but on all of us as a community to dedicate to working with EB patients. But our implications for change on the first side is understand and know our patient. We just saw the importance of the proper diagnosis, classification on type and subtype, but also for understanding how our patients behave.
We have to individualise it during the consult. We normally have 15 or 20 minutes for the visit, so we develop this ABCDE in EB patients for healthcare professionals. Works perfectly well in Spanish. In English, we have to do some adaptations, and the first one is the A about the blisters. Important to understand how are they located, how often do they present, and classify and try to measure pain and each in every consult. With the B, we have this baseline. Understanding if there is any digestive symptoms, how are the bowel habits, if there are any medications that all the patients are having. On the C, we need to understand how are the cure, how are the dressing changes doing for every patient? How often do they do it? What type and how many bandages do they use? And if they need any antibiotics, healing painkillers before then the cure. For the D, we have the comorbidities associated. It's very important to registrate about the anaemia, squamous cell carcinoma, malnutrition among others. And also with the E, with the exams and test and a specialist involved. At least we need to do test one per year, one time per year, but it's always important to register it on the clinical chart. Another thing very important is to make a proper name of the wounds that all of our patients have. Trying to understand how often, if they're acute, they're chronic, they're recurring, and if some of them represents activity or dose, or damage of the disease. And we can do it during the registration or the the EBDASI with these five sections. The first section on the skin, the second on the scalp, the third one on the mucus membranes, the fourth is about the nails on the hands and toes, and the fifth section of the EBDASI is to register all the different lesions and comorbidities that our patients has.
It's important in two aspects, not only classification and do a correlation with between mild and severe disease, but also for the follow-up, especially on the severe cases. Another thing that is very important is even though this patient has recessive dystrophic EB, with a lot of activity and damage just to differentiate the type of wounds, especially the partial thickness wounds where we can do a registration, and also some of the treatments available. In this, we can do a register with this body surface area, partial thickness wounds scar, and just remember that the wounds in EB are not perfect squares. They have these geographical forms that we have to register in the [indistinct] for kids, and also for adults. If you want to introduce a new treatment, a new option in the daily care of every patient, you need to talk about it before, during the treatment, and after the treatment. Before because it's really important to explain how to use it during the treatment. It's important to set, to explain what we are looking for, what our expectations, and on the follow up on the long-term treatment, it's important just to keep the adherence of the treatment, and also to understand that it's important not to do a quick stop, or just forget about the treatment. So having this open conversation is essential, but also essential for the adherence of the treatment, but also to explain to them how to use it. It's always important to say that it's a single use medication that even though it's a small tube, can cover a lot of big areas like the ones we can have here.
The beginning we were trying to calculate it with formulas, we were explaining to them directly, but I think with the images not only for the patients and caregivers, it's important to see how many wounds they can treat, but also for the physicians to do the follow up to be able to know how many tubes we'll have to prescribe. Where we have this knee with this 10 square centimetres wound. So that means you can treat 25 wounds like this. Or if you have this foot and you see like, 10 centimetres long with a three or two and a half is a width area, give us like 25 square centimetres. If you wanna do it like calculations and mathematics, you can maybe be in trouble, but if you see like these portion of the foot has a 25 square centimetres wound, you can treat 10 wounds like this. So I think it's important to understand perfectly well how to use it and apply it for the local regulations. And then the how to use it, it's always important to select the proper wounds and do it. You can apply the medication directly on the dressing or directly on the wound.
Just remember it's always one millimetre of thickness, and it's important to always cover the wound treated with the right bandage. In our practising for the last years, we include 13 patients that couldn't be included on the EASE trial because of the exclusion criteria with very severe dystrophic EB. On these patients, what we notice is a reduction of the body surface area of partial thickness wounds when applied. Data consistent with what we've seen, we have been seeing in the EASE study, and also a reduction on the EBDASI skin activity and skin damage. The product is well tolerated in this image on the right side. It's you can see a kid applying the medication all over his body with a well tolerated, nice smell, nice texture. But on this two years follow up where we can notice, it's the majority of the patients were able to return to school and work. They report a change in the mood/self-esteem, and the increase in the quality of the sleep among other changes. That's why we are now recommending this just to have it keep in mind that one tube can cover a lot of area. It's important to remind a lot of all of our patients that it's a single use tube. That is a self-administration gel that can be used directly or in the bandages, but always in the company of bandages. Not just leave the product alone. And at least do a change every four days just being able to allow the product to work.
