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. Objectives 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.

A Multicenter, Randomized, Open-Label, Controlled Study Comparing the Efficacy, Safety and Cost-Effectiveness of a Sequential Therapy with RV4104A Ointment, Ciclopiroxolamine Cream and Ciclopirox Film-Forming Solution with Amorolfine Nail Lacquer Alone in Dermatophytic Onychomycosis

“…It is striking to realize that the complete cure rates obtained in this study are of the same magnitude as complete cure rates obtained with oral antifungals [9] . However, any external comparison should be interpreted with caution as patient populations may be different across studies.…”

“…Complete cure of onychomycosis with oral antifungals can be achieved in 25-30% of patients at 1 year according to recent studies with the most effective agents [8] . Once onychomycosis is cured, the frequency of relapses or reinfections is high and concerns up to 50% of patients [9,10] . In addition, oral antifungal agents due to their hepatic metabolism through cytochrome P450 3A4 (azoles) or cytochrome P450 2D6 (terbinafine) may be associated with drug interactions [11] .…”

Therapeutic efficacy of topical OLEOZON® in patients suffering from onychomycosis

“…This assay demonstrated the fungicidal activity of topical OLEOZON Ò , better than others reported in literature, even oral treatments. [18][19][20][21][22][23] This product has a great action spectrum, does not create pathogen resistance, has a good tissue diffusion and is well tolerated by patients without any adverse reactions. [25][26][27][28][29][30][31][32] In comparison, topical ketoconazole failed to reduce the fungal burden in the affected nails with only slight improvements in the third month of treatment.…”

“…The low number of relapses in the cured patients, who had been treated with OLEOZON Ò (2.8%), during the 1 year of follow-up, is encouraging. Some authors suggest that this product is superior to other commonly used topical or oral antimycotics 6,[9][10][11]21 and acts as a great fungicide against T. rubrum and C. albicans.…”

“…Imidazole derivatives (ketoconazole, itraconazole and fluconazole), which are wide-spectrum antimycotics, seem to be more effective than griseofulvin, but are also very expensive, as is the case with terbinafine. A combination of long-term oral and topical therapies, when given at the same time, yield good clinical outcomes, 6,[18][19][20][21][22][23] although there remains a need for more effective topical agents with greater nail penetration that can avoid unnecessary use of oral antifungal agents, thereby avoiding their side effects.…”