Skin wound type may be key to designing clinical trials for RDEB
Patients can have chronic, open wounds or recurrent wounds
People with recessive dystrophic epidermolysis bullosa (RDEB) have two different kinds of wounds — chronic open wounds that are larger, more painful, and slow to heal, and recurrent wounds that repeatedly close and reopen, but almost always heal on their own.
These findings from a new study suggest that failing to account for wound type could confound results in clinical trials, where rates of healing are often a primary measure of effectiveness. “Future RDEB studies should consider wound type as the main stratification factor in clinical trial design as wound type appears to be a key predictor of wound healing,” wrote the study’s researchers, who had participants use a mobile app to upload weekly photos of their wounds over several months to capture real-world healing patterns. Doing it this way, reduced the need for in-person visits and may broaden access to RDEB trials, they said.
The study, “Natural history study of recessive dystrophic epidermolysis bullosa wounds and patient reported outcomes using mobile application home photography,” was published in Scientific Reports.
Epidermolysis bullosa (EB) refers to rare genetic disorders that make the skin extremely fragile. While it can affect multiple organ systems, the most frequent and burdensome symptoms are skin wounds, pain, and itch. In dystrophic EB, skin weakness is related to blistering in the skin’s lower layers and is caused by mutations in the COL7A1 gene that encodes type VII collagen. RDEB is a specific subtype wherein mutated copies of the gene are inherited from both parents.
The researchers previously identified two types of RDEB wounds — chronic open wounds that stayed open for about three months and recurrent wounds that healed more quickly, but reopened.
“Despite these breakthroughs, there remains a lack of understanding of how often RDEB wounds may heal then re-blister, and this gap in knowledge of the placebo response in wounds limits clinical trial design and the interpretation of results,” wrote the researchers, who said tracking how RDEB wounds heal requires frequent evaluations over time, but traveling to clinics is often difficult for patients because of their fragile skin. In this study, 13 patients uploaded photos from home, tracked up to six wounds a week for up to six months and letting the researchers compare the natural course of chronic open wounds with recurrent wounds. The participants, whose RDEB was genetically confirmed, were an average age of 26.
Comparing different types of wounds in RDEB
Examining if the wounds closed within 12 weeks showed the researchers that 60.9% of the injuries were chronic open wounds, while 27.5% were recurrent wounds. The remaining ones were of an indeterminate type.
At the study’s beginning, the chronic open wounds were, on average, 10 times larger than recurrent wounds. They also tended to be more painful, although both itched about equally.
During the observation period, all the recurrent wounds healed spontaneously, without treatment, after a median of 5.7 weeks, but only 17% of the chronic, open wounds closed after nearly six months.
The results compared with those of a separate group of participants who had monthly in-clinic evaluations and who participated in the placebo arm of the Phase 3 ESSENCE clinical trial (NCT02384460). That study tested the efficacy of an investigational topical allantoin cream (SD-101) for RDEB wound closure.
The general agreement between the groups suggested that uploading images at home may be an effective alternative to regular clinic visits for studies in this population, said the researchers, who did note that the first group was relatively small, and not all the participants uploaded images every week.
In the ESSENCE group, a statistical model predicted that recurrent wounds were 29 times more likely to close on their own than chronic, open wounds. This was after adjusting for participants’ age, wound location, and starting wound size.
The findings suggests clinical trial investigators should consider wound type when measuring treatment-related outcomes.
“Any imbalance in wound types in treatment [versus] placebo groups would abrogate the ability of a clinical trial to detect a true drug response,” wrote the researchers, who also suggested different time courses for the two wound types in clinical studies. As chronic, open wounds rarely resolve on their own, trials that last two to three months could be sufficient for capturing changes with treatment, but because recurrent wounds can close independently, assessing longer-term results for them might be better. “Recurrent wound endpoints should assess the durability of wound closure at multiple time points,” they wrote.
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