WAIKOLOA, HAWAII (FRONTLINE MEDICAL NEWS) – The topical vasoconstrictor brimonidine 0.33% gel brings impressive improvement in the facial redness component of rosacea, but it does nothing to address the inflammatory lesions of the disease, Dr. Joseph F. Fowler, Jr., said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Rebound flushing wasn’t seen in the 52-week, large, open-label safety study of brimonidine gel, but has been anecdotally reported since its approval. Flushing occurs 12-24 hours after application, and usually lasts a day or two, according to Dr. Fowler, who was the first author of several multicenter randomized trials of the therapy.

“The rebound phenomenon is not something that frightens me or others I know who use the medication routinely, because it’s not something that’s going to cause a long-term problem,” he declared. Indeed, once brimonidine gel (Mirvaso) has quelled the erythema, the inflammatory lesions will stand out even more prominently, noted Dr. Fowler, the conference co-director and a dermatologist at the University of Louisville. “You’ve got to do something about the inflammatory component.”

Two topical therapies that address the inflammatory component include ivermectin 1% cream (Soolantra), shown to reduce counts of papules and pustules in two 40-week extension studies of phase III trials ( J Drugs Dermatol. 2014 Nov;13[11]:1380-6 ), and azelaic acid 15% foam (Finacea), which also achieved an impressive reduction in inflammatory lesion counts in a phase III trial ( Cutis. 2015 Jul;96[1]:54-61 ).

Both agents were well tolerated in those studies. That’s a major treatment consideration because rosacea patients have elevated facial skin sensitivity and often can’t tolerate older off-label topical therapies because of stinging and burning, according to Dr. Fowler.

Some rosacea patients are so intolerant of topicals that they prefer oral therapy. For those patients, subantimicrobial-dose doxycycline is a good option, Dr. Fowler said.

In addition to its anti-inflammatory effects, topical ivermectin kills Demodex. While rosacea is an inflammatory disorder, not an infection, drugs like ivermectin and crotamiton 10% cream (Eurax) that kill Demodex also improve rosacea, he observed.

The initial irritation event rate with azelaic acid 15% foam in the phase III trial was in the 2%-5% range, and those events were short lived. Irritation is a much bigger problem with the older azelaic acid 15% gel, with event rates in the 15%-25% range.

Dr. Fowler has also had good results using topical calcineurin inhibitors off-label for rosacea. Pimecrolimus cream (Elidel) is in ongoing studies for treatment of seborrheic dermatitis, which often coexists with rosacea, he noted.

He reported serving as a consultant to half a dozen pharmaceutical companies, including Galderma, which markets ivermectin cream and brimonidine gel, and Bayer, which markets azelaic acid foam.

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