Long-term efficacy of antifungals in toenail onychomycosis: a critical review

Background Modern antifungal drugs achieve high mycological and clinical cu re rates in onychomycosis of the toes, but little is known about the long-t erm evolution of the treated patients. Objectives The aim of this review was to analyse the therapeutic results re corded more than 1 year after initiation of therapy. Methods We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the nu mber of patients with negative mycology at week 48). Clinical cure rate (EP clin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0. Results From a Medline search we identified 17 studies providing results be yond 48 weeks. Ketoconazole 200 mg d(-1) up to 1 year resulted in EP1 of 11 % at 18 months, and EP2 of 43%. Griseofulvin 1 g d(-1) for 1 year allowed a n EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole o nce weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itracon azole 200 mg d(-1) or 400 mg d(-1) for 1 week each month for 3-4 months, EP 1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbina fine 250 mg d(-1) for 12-16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, a nd 71% at 4 years. In the only study planned to compare the longterm effica cy of terbinafine and itraconazole, EP1 at 18 months was significantly high er with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P < 0.001). The clinical cure rates were 21% at 60 weeks and 37% at 7 2 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years wi th itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 y ears with terbinafine. Conclusions Considering the stringency of the criteria we used, this critic al review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.