Study Compares Pulse vs Continuous Therapy for Dermatophyte Toenail Onychomycosis

Doug Brunk

June 24, 2020

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

"Previous meta-analyses of pulse and continuous therapies have generated ambiguous results," study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. "There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole."

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

"Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150–450 mg), it is not significantly different from the other included treatments," Dr. Gupta and colleagues wrote in the abstract. "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. 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 went on to note that, in clinical practice, "neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the 'off' period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis."

The study was awarded fourth place in the AAD's 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada .

American Academy of Dermatology (AAD) 2020 Annual Meeting: Abstract 16014.

This article originally appeared on MDEdge.com.

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