Pulse Therapy Versus Continuous Therapy for Toenail Onychomycosis

Onychomycosis is a persistent fungal infection of the nails and adjacent skin, manifesting as discoloration, thickening of the nail, and onycholysis. A meta-analysis compared pulse and continuous systemic therapies (terbinafine, itraconazole, and fluconazole) for toenail onychomycosis. Researchers observed no differences in efficacy or safety between pulse therapy and continuous regimens of terbinafine or itraconazole. The results of the study were published as part of the American Academy of Dermatology Virtual Meeting Experience 2020.

The systemic review included randomized, controlled trials assessing antifungal treatments for toenail dermatophyte onychomycosis in English-speaking adults diagnosed via potassium hydroxide and culture. Final analysis included 22 studies from 20 publications, including 4,205 randomized patients.

When comparing monotherapies with placebo, there was a significantly greater risk ratios (RR) of achieving mycological cure with all treatments. The most successful treatments, compared with placebo, were continuous terbinafine 250 mg daily for 24 weeks (RR, 11; 95% confidence interval [CI], 6.08-19.30) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90; 95% CI, 4.16-16.40).

Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycological cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it was not significantly different from the other included treatments.

Adverse events were not significantly different among any treatment or placebo cohorts.

“Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores,” the researchers noted. “During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They concluded that, in practice, neither continuous nor pulse therapy is better, as published evidence demonstrated no difference in the safety and efficacy between pulse therapy and continuous regimens of terbinafine and itraconazole.

Gupta AK, Stec N, Bamimore MA, et al. The Efficacy And Safety Of Pulse Vs Continuous Therapy For Dermatophyte Toenail Onychomycosis. Presented during the AAD Virtual Meeting Experience 2020, June 12-14, 2020.