Topical Treatment of Onychomycosis and Clinically Meaningful Outcomes

Onychomycosis is the most common nail disease in adults, representing up to 50% of all nail disorders, and nearly always associated with tinea pedis.^1,2 Disease severity is usually classified according to extent of infection: described as mild (25% or less nail involvement), moderate (26–74% involvement), or severe (more than 75% involvement).² In a prospective, multicenter survey of 15,000 patients visiting physician’s offices, of those diagnosed with distal lateral subungual onychomycosis (DLSO) the majority had moderate (39.9%) or severe (32.5%) disease.² Six pivotal phase III studies have reported the efficacy and safety of topical antifungal treatment in over 3300 mild-to-moderate patients with DLSO.^3-5 As would be expected from epidemiology data, the majority of patients in these studies were male (78.8%) with a mean age a little over 50 years old. The mean area of involvement of the target toenail was approximately 40%.^3-5 Although demographic reporting is not consistent, the mean number of affected non-target toenails (3),^4,5 and the mean duration of onychomycosis in the target toenail (11 years),³ may also be indicative that patients in the pivotal studies on topical treatment of onychomycosis had predominantly moderate disease. In a post hoc analysis of the two pivotal studies with efinaconazole topical solution (10%) three quarters of patients (75.0%) had moderate onychomycosis.⁶Efficacy of topical onychomycosis treatment has been widely reported and reviewed.^3-5 The primary efficacy endpoint in the pivotal studies was complete cure (0% clinical involvement of target toenail and both negative potassium hydroxide (KOH) examination and fungal culture) at week 52. Reported complete cure rates were 5.5% and 8.5% (ciclopirox),3 6.5% and 9.1% (tavaborole),⁵ and 15.2% and 17.8% (efinaconazole).⁴Onychomycosis is a progressive disease; supported by the efinaconazole clinical data showing a tendency to both greater target toenail involvement and more affected non-target toenails with increased disease duration.⁷ Toenail onychomycosis also frequently involves several nails.^2,8 It has been suggested that greater non-target toenail involvement could result in reduced treatment efficacy.⁹ However, one study failed to demonstrate any prognostic value of the extent of nail involvement, or the number of toenails involved.¹⁰ Patients with a history of prior infection, those with untreated tinea pedis, men and older patients were less likely to reach clinical cure.¹⁰ Post hoc analyses of the two efinaconazole studies reported greater complete cure rates in mild onychomycosis,⁶ females,¹¹ and in patients with a baseline disease duration of less than one year or where no other toenails were involved.⁷ However, these findings are based on strictly controlled clinical studies of a fixed 48-week treatment duration and several investigators have suggested that longer treatment courses could result in better outcomes for many more patients. In addition, many