title: Long-term efficacy of antifungals in toenail onychomycosis: a critical review.
abstract: BACKGROUND
  Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients.
  
  
  OBJECTIVE
  The aim of this review was to analyse the therapeutic results recorded 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 number of patients with negative mycology at week 48). Clinical cure rate (EPclin) 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 beyond 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 an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d(-1) or 400 mg d(-1) for 1 week each month for 3-4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 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, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher 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 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine.
  
  
  CONCLUSIONS
  Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.
authors.affiliation: Clinique Dermatologique des Hôpitaux Universitaires, 1 place de l'Hôpital 67091 Strasbourg, France. Bernard.Cribier@chru-strasbourg.fr
authors.forename: B J
authors.initials: BJ
authors.lastname: Cribier
authors.forename: C
authors.initials: C
authors.lastname: Paul
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005533:Foot Dermatoses / Q000188:drug therapy; D006801:Humans; D009281:Naphthalenes / Q000627:therapeutic use; D014009:Onychomycosis / Q000188:drug therapy*; D000077291:Terbinafine; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine