The Efficacy and Safety of Pulse vs. Continuous Therapy for Dermatophyte Toenail Onychomycosis

The Efficacy and Safety of Pulse vs Continuous Therapy for Dermatophyte Toenail Onychomycosis

TAKE-HOME MESSAGE

• This systematic review and network meta-analysis showed that continuous daily and pulse regimens of terbinafine and itraconazole were similar in mycological cure. Continuous terbinafine 250 mg daily for 12 weeks was not significantly different from continuous terbinafine 250 mg for 16 and 24 weeks, pulsed terbinafine 500 mg, weekly fluconazole, or pulsed and continuous itraconazole regimens in mycological cure. Continuous daily terbinafine 250 mg for 24 weeks performed best in rank probabilities over other therapies, but the clinical significance of this is debated.

• Continuous and pulsed regimens of terbinafine and itraconazole for onychomycosis had similar efficacies and adverse events. Whether dosing of daily terbinafine 250 mg for longer than the FDA-approved 12 weeks yields higher efficacy could be investigated in larger studies.

– InYoung Kim, MD, PhD

Abstract 

BACKGROUND

Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear.

OBJECTIVE

To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple-treatment meta-analysis.

METHODS

This systematic review and network meta-analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta-analysis.

RESULTS

The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks - but not 12 weeks - was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9-12 months. Rank probabilities demonstrated that 24-week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events.

CONCLUSION

More knowledge about the fungal life cycle and drugs' pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.

Journal of the European Academy of Dermatology and Venereology: JEADV

The Efficacy and Safety of Pulse vs. Continuous Therapy for Dermatophyte Toenail Onychomycosis

J Eur Acad Dermatol Venereol 2019 Nov 20;[EPub Ahead of Print], AK Gupta, N Stec, MA Bamimore, KA Foley, NH Shear, V Piguet 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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