LONDON – , in a small, placebo-controlled, phase 2 study.
Sara Freeman/MDedge News
Dr. Cristina Guttman-Gruber
More importantly, use of the ointment promoted wound healing in those with the severe skin-blistering condition. Indeed, compared with placebo, a greater reduction in wound size was observed after 2 weeks when the ointment was applied (a mean reduction of 65.5% vs. 88.4%; P less than .006). However, at 1 month, no significant differences were seen in the size of the wounds between the two treatment arms.
“Calcipotriol is a vitamin D analog and it is well known that vitamin D is a very critical factor for skin homeostasis and proper wound healing,” Christina Guttmann-Gruber, PhD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). Dr. Guttmann-Gruber, a group lead researcher for EB House Austria, which is based at the Salzburg (Austria) University Clinic for Dermatology, noted that vitamin D also helps with tissue repair and immune modulation, and enhances local antimicrobial activity.
During an oral poster presentation at the meeting, Dr. Guttmann-Gruber explained that in previous in vitro studies, it was found that low concentrations (100 nmol) of calcipotriol inhibited proliferation of RDEB tumor cells (Sci Rep. 2018 Sep 7;8:13430). Calcipotriol (also known as calcipotriene) also was found to improve the expression of antimicrobial peptides and promote wound closure. “Therefore, we thought that applying calcipotriol at the site of injury, on chronic wounds prone to superinfection where it is needed, might be beneficial for our patients.”
She and her associates designed a two-arm, randomized, double-blind crossover study to assess the effects of an existing calcipotriol-containing ointment on wound healing in patients with RDEB. The ointment used in the study is approved for treating psoriasis but was adapted by the in-house pharmacy team to reduce the concentration of calcipotriol to about 0.05 mcg/g, or around 121 nmol. The reason for the reduction was that, at higher doses, keratinocyte proliferation was reduced, which would be detrimental in RDEB patients.
Nine patients were included in the study and were randomized to either apply 1 g of the active or placebo ointment to each of two designated wounds, of at least 6 cm2 in size, every day for 4 weeks. A 2-month washout period then followed before the groups switched to use the other ointment for 1 month. Six out of the nine patients completed both treatment phases. The reasons for the patients not completing both intervention phases were not related to the drug.
Calcipotriol treatment resulted in a significant and steady reduction in itch over the entire course of treatment, which was not seen among those on placebo, Dr. Guttmann-Gruber observed. The reduction in itch was “striking,” but only while the treatment was being used, she said. Results for pain were less clear, with a significant reduction in pain after 2 weeks seen only in the placebo group, while both treatments reduced pain to the same degree by 1 month.
No serious adverse events were observed at any time point and topical use of the low-dose calcipotriol did not significantly change serum levels of calcium or vitamin D in the two patients in which this was studied, Dr. Guttmann-Gruber said.
“This is an approved drug; it’s used in psoriasis, but at a very high concentration. We were able to use it off label and make a diluted version,” she observed. “Any pharmacy can do it.” Although it was applied topically, it could be done by applying it to the dressing rather directly onto the wounded skin, she said.
Data on the skin microbiome response to treatment were also collected but were not available to analyze in time for presentation, but it appeared that there was improvement with the low-dose calcipotriol treatment, Dr. Guttmann-Gruber said. “When the wounds are healing, the microbial flora is improving.”
The next step will probably be to plan a multicenter trial of this treatment, Dr. Guttmann-Gruber said in an interview. The questions is whether such a trial would get the financial backing it needed, but if an orphan drug designation could be obtained for calcipotriol for EB, then it would be possible to conduct such a trial.
The study was funded by DEBRA Austria. The presenting author, Dr. Guttmann-Gruber, had no conflicts of interest to disclose.
SOURCE: Guttmann-Gruber C et al. EB World Congress 2020. Poster 34.