BERLIN — Isotretinoin could be headed for a new indication as a licensed treatment for rosacea.
The workhorse oral retinoid has been used off label to treat challenging cases of rosacea for more than 2 decades. However, Barcelona-based Almirall recently sponsored a successful multicenter randomized trial aimed at earning an indication from regulatory authorities for its branded version of isotretinoin in the treatment of rosacea, Dr. Harald Gollnick said at the annual congress of the European Academy of Dermatology and Venereology.
The double-blind, 12-week study involved 224 patients with the papulopustular or phymatous forms of rosacea. Participants in the five-armed trial were randomized to isotretinoin at 0.1, 0.3, or 0.5 mg/kg per day; doxycycline at 100 mg per day followed by 50 mg per day; or placebo, explained Dr. Gollnick, professor of dermatology at Otto-von-Guericke University, Magdeburg, Germany, and president of the European Board of Dermato-Venereology.
The optimal isotretinoin dose proved to be 0.3 mg/kg per day. Its efficacy was superior to placebo and similar to that of doxycycline, with both regimens achieving a 90% reduction in papules and pustules at 12 weeks, according to Dr. Gollnick, who is also chairman of the Global Alliance to Improve Outcomes in Acne, an international group of acne experts.
“That means in the near future we'll most probably have an on-label indication for isotretinoin in rosacea,” he said.
Over the years isotretinoin has been used off label to treat rosacea, but the best dose was a matter of guesswork. The Almirall-sponsored trial is particularly welcome because it is the first formal study aimed at defining the optimal dose, added Dr. Gollnick.
The 0.3-mg/kg dose was associated with a low rate of side effects, consisting mainly of mild lipid changes and liver enzyme elevations. The 0.5-mg/kg dose wasn't any more effective, and it produced more irritation and facial dermatitis. The 0.1-mg/kg dose, while significantly better than placebo, was less effective than 0.3 mg/kg.
Topical therapies for rosacea include 0.5%-2% metronidazole, azelaic acid, 0.025% tretinoin, and 2.5%-5% permethrin. Systemic treatments include metronidazole at 500 mg/day, minocycline at 50 mg/day, tetracyclines at 0.5–1.5 g/day, and the subantimicrobial formulation of doxycycline known as Oracea.
Dr. Gollnick is a consultant to Almirall and numerous other pharmaceutical companies.