PracticeUpdate Dermatology Best of 2018

CONFERENCE COVERAGE 30

Do Not Delay BrimonidineWhen Using Combination Therapy for Rosacea Initiating it along with ivermectin immediately helps speed clearing of inflammatory lesions.

I nitiating a combination of brimonidine plus iver- mectin topical therapy immediately, rather than the more standard approach of adding brimonidine only after pustules and papules have cleared, leads to a more rapid resolution of moderate-to-severe rosacea, according to a study presented at the meeting. Rosacea, particularly in its more severe forms, fre- quently presents as a combination of inflammatory papules and pustules that occur in a background of erythema, presenter Linda Stein Gold, MD, of Henry Ford Health System in Detroit told Elsevier’s Prac- ticeUpdate . A common treatment approach is to address the papules and pustules first with a treatment such as ivermectin 1%, and then address the erythema with an α-2 adrenergic agonist such as brimonidine. What has remained unclear is whether waiting for the papules and pustules to clear before addressing the background erythema is the most efficient approach to therapy. To find out, Dr. Stein Gold and colleagues conducted a multicenter, randomized, double-blind, vehicle-controlled study in which patients with mod- erate-to-severe rosacea with an Investigator Global Assessment (IGA) of 3 or more were randomized to one of three groups: 1. Once-daily treatment in the morning with brimoni- dine 0.33% combined with once daily treatment in the evening with ivermectin 1% for 12 weeks (n=49). 2. Once daily treatment with brimonidine vehicle in the morning for 4 weeks, followed by treatment with active brimonidine therapy for 8 weeks, com- bined with ivermectin treatment in the evening for 12 weeks (n=46). 3. Morning treatment with brimonidine vehicle com- bined with evening treatment with ivermectin vehicle for 12 weeks (n=95).

All patients were counseled to follow a general skin care regimen consisting of a cleanser, moisturizer, and sunscreen that were provided or recommended. At week 12, hour 3, 55.8% of the total population of patients treated with active therapy (n=95) were rated as “clear” or “almost clear” on the IGA, compared with 36.8% in the vehicle group (P = .007). In addi- tion, 61.2% of the patients who received active therapy for the entire 12 weeks achieved this rate of clearing, compared with 50% of those who only received brimo- nidine for 8 weeks. Outcomes were only significantly different from the vehicle group among those treated with both therapies for the full 12 weeks (P = .003). When measured at week 12, the rate of successful clear- ing increased fromhour 0 to hour 3 among patients using brimonidine. In patients who received both active thera- pies for 12 weeks, the rate of successful clearing almost doubled from hour 0 to hour 3, from 32.7% to 61.2%. Compared with the vehicle-alone group, the two sub- group of patients who received active therapy had significantly greater improvements in the Clinician’s Erythema Assessment (CEA, P < .015). At 12 weeks, 16.3% of patients in the 12-week active therapy group had 100% reduction in inflammatory lesion count, compared to 4.2% of those who received the vehicle alone (P = .015). Results were intermediate for those who received only 8 weeks of brimonidine, with 6.5% achieving 100% clearing of inflammatory lesions. Overall, eight treatment-related adverse events were reported in six subjects, including treatment-related worsening of rosacea in one patient on active therapy and three using vehicle alone. One patient on active therapy discontinued because of the development of allergic dermatitis on the chest. Dr. Stein Gold expressed surprise at the findings. “It was really contrary to what we expected,” she said. “We did not expect that starting these two drugs together would have any effect on the overall efficacy of treating the inflammatory lesions, and what we found was that the number of patients who got completely clear was signif- icantly higher when we started the two drugs together than when we delayed the brimonidine by a month.” “This has changed the way I practice,” she said. “I was always a fan of waiting to start the α adrenergic agonist until the inflammatory papules were under con- trol.” She speculated that brimonidine itself may have some anti-inflammatory properties, which have been demonstrated in animal models. “It might be that the combination of the two products both contribute dif- ferently to the anti-inflammatory effects.” “This just highlights that generally when you use com- bination therapy with drugs that work by different mechanisms of action, we generally see an improve-

Dr. Linda Stein Gold

ment in the overall efficacy.” www.practiceupdate.com/c/64580

Courtesy of the AAD

PRACTICEUPDATE DERMATOLOGY