Topical sirolimus gel clinically effective for systemic rare vascular malformations

Several clinical trials have been conducted of sirolimus, an inhibitor of the mechanistic/mammalian target of rapamycin complex 1, for the treatment of vascular malformations. The efficacy of sirolimus has not been established for capillary and venous malformations, aside from lymphatic malformations. Additionally, no generalized venous or capillary malformations have been treated with topical sirolimus.

Mari Wataya-Kaneda, Graduate School of Medicine, Osaka University, Osaka, Japan, and colleagues conducted an open-label single-arm pilot study with 0.2% sirolimus gel from 2019 to 2020 to evaluate the efficacy and safety of topical sirolimus for capillary and venous malformations. They also compared the efficacy of systemic and topical sirolimus therapy.

The study included four patients diagnosed with different vascular malformations (common venous malformation, blue rubber bleb nevus syndrome, angiokeratoma in Fabry disease, and phakomatosis pigmentovascularis type IVb).

The study's primary endpoint was calculated as the safety evaluation of sirolimus gel. The main secondary endpoint was the improvement rate evaluated by the Central Judgment Committee at 12 weeks using photographs.

The researchers reported the following findings:

• No adverse events were observed.
• Blood sirolimus was not detected in any patient.
• 50% of the patients had mild improvement, and the remaining 50% of patients showed no change after 12 weeks of treatment.
• Blue rubber bleb nevus syndrome, a generalized venous malformation, showed the greatest response.
• Treatment response varied with different lesions in the same patients.

"We found 0.2% sirolimus gel to be as clinically effective as systemic sirolimus treatment in patients with venous and capillary malformations and more effective for early active lesions, even systemic venous malformations," the researchers concluded.

Reference:

Wataya-Kaneda, M., Maeda, S., Nakamura, A., Hayashi, M., & Fujimoto, M. Verification of the efficacy of topical sirolimus gel for systemic rare vascular malformations: A pilot study. The Journal of Dermatology. https://doi.org/10.1111/1346-8138.16930