AMSTERDAM – The combination of fixed-dose adapalene/benzoyl peroxide plus oral doxycyline is a reasonable alternative to oral isotretinoin in patients with severe nodular acne, according to the findings of a phase IIIb randomized head-to-head comparative study.
The topical/oral combination is a particularly attractive option for those patients who aren’t candidates for the potent oral retinoid, are unwilling to take it, or can’t tolerate its side effects, Dr. Jerry Tan said at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Tan presented the results of the phase IIIb POWER trial, a 20-week, multicenter, randomized investigator-blinded study involving 266 patients with an average age of 19 years. Participants were randomized to adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo)plus oral doxycyline hyclate at 200 mg/day or to placebo gel plus oral isotretinoin at 0.5 mg/kg per day for the first 4 weeks and 1.0 mg/kg per day for the remaining 16 weeks.
At 2 weeks, patients in the combination treatment group averaged a 40% reduction in facial nodules, compared with baseline, versus a 24% decrease with isotretinoin. The combination treatment group also averaged a 27% reduction in facial papules and pustules, an effect size twice that seen in the isotretinoin group at that point. The combination therapy group had a 13% decrease in comedones, compared with 6% with isotretinoin, reported Dr. Tan, a dermatologist at the University of Western Ontario, London.
Dr. Jerry Tan
By the study’s end at week 20, however, isotretinoin showed superior efficacy. But this came at the cost of a significantly worse safety profile. Indeed, the only truly serious treatment-related adverse event seen in the study – a case of Stevens-Johnson syndrome requiring hospitalization – occurred in a patient on isotretinoin.
In an effort to capture both the strengths and drawbacks of each treatment strategy in a single metric, Dr. Tan and his coinvestigators came up with a prespecified novel endpoint they termed “the composite success rate.” They defined it as at least a 75% reduction in a patient’s nodule count, plus the absence of treatment-related, medically relevant adverse events. Based on this measure, the fixed-dose topical plus oral doxycycline regimen was more effective, with a 74% composite success rate, compared with 58% for isotretinoin.
The trial was funded by Galderma. Dr. Tan disclosed serving as a paid researcher for and consultant to Galderma and other pharmaceutical companies.