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Continuous terbinafine most effective for toenail onychomycosis

Presented by
Dr N Stec
AAD 2020
A systematic review investigating efficacy and safety of continuous versus pulsed therapy for treating toenail onychomycosis revealed no significant beneficial regimen in general. However, mycological cure had the greatest success with continuous terbinafine 250 mg over 24 weeks [1,2].

Onychomycosis is the most common of all nail diseases and has different treatment options. A network meta-analysis aimed to examine the most effective of these treatment options with regard to mycological cure. The analysis included 22 studies with data from 4,205 study subjects and targeted randomised controlled trials of oral antifungal therapy for adults for toenail onychomycosis, diagnosed by potassium hydroxide solution (KOH) and culture. The assessment evaluated terbinafine, itraconazole, and fluconazole in continuous and pulsed regimes at different dosages: 250 mg terbinafine (continuous for 12, 16, and 24 weeks), 500 mg terbinafine (pulsed for 3 or 4 months), 200 mg itraconazole (continuous for 12 weeks), 400 mg itraconazole (pulsed for 3 or 4 months), and fluconazole 150 mg, 300 mg, or 450 mg (once a week over 9-12 months).

Evaluation against placebo resulted in superiority in attaining mycological cure for all monotherapies. The Surface Under the Cumulative Ranking (SUCRA) value for likelihood of mycological cure versus placebo was highest (95.97) for the 24-week continuous daily intake of 250 mg terbinafine with a relative risk (RR) of cure at 11.0. Second in ranking was terbinafine at the same dosage over 16 weeks (RR 8.9) with SUCRA 70.71, while 3 months of pulsed treatment with terbinafine had a SUCRA of 58.78. SUCRA 47.20 and 43.98 were seen for 3 and 4 months of pulses with itraconazole 400 mg, whereas 12 weeks of continuous itraconazole 200 mg resulted in a SUCRA of 33.87. Fluconazole at all doses was less efficacious than the other agents.

Comparisons of application schedules revealed no significant differences in probability of mycological cure between the continuous and pulsed regimens of terbinafine and itraconazole. As the authors point out, this result was unexpected because pulsed therapy was theoretically more effective considering the fungal life cycle: the sudden high concentration of an anti-fungal drug eliminates hyphae, sparing already present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. In practice, this advantage could not be shown. In terms of adverse events, safety of all the anti-fungal agents was comparable with placebo.

  1. Stec N, et al. P16014, AAD Virtual Meeting Experience, 12-14 June 2020.
  2. Gupta AK, et al. J Eur Acad Dermatol Venereol. 2020;34:580-88.

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