Recurrences of Dermatophyte Toenail Onychomycosis during Long-Term Follow-up after Successful Treatments with Mono- and Combined Therapy of Terbinafine and Itraconazole

Abstract

The influence of dosing regimens on the recurrence rates of onychomycosis has not been investigated. To compare recurrence rates for toenail dermatophyte onychomycosis between four dosing regimens. A prospective, investigator-blinded, long-term follow-up (1.25 to 7 years postenrolment) study of the following regimens was undertaken with or without booster therapy at week 36: overlapping continuous itraconazole and terbinafine (COMBO), continuous terbinafine (CTERB), intermittent terbinafine (TOT), and pulsed itraconazole (III). One hundred six mycologically and 43 completely cured participants at week 48 were included. Recurrence rates (RR) for mycologically and completely cured participants were respectively termed mycologic recurrence (MRR) and complete cure recurrence (CRR) rates. No statistically significant difference was detected between the four regimens for the two rates. However, lower MRRs were obtained for CTERB (32%) and TOT (36%) compared to III (59%) and COMBO (57%). When participants who received booster therapy were excluded from the analysis, the MRR was lower for CTERB (21%) compared to TOT (39%). Itraconazole therapy was associated with higher RRs than terbinafine therapy. Combined therapy did not reduce the RRs compared to monotherapies. A difference might exist between continuous and intermittent antifungal regimens, but additional randomized clinical trials are needed for confirmation.