Topical Treatment of Onychomycosis and Clinically Meaningful Outcomes

October 2016 | Volume 15 | Issue 10 | Original Article | 1260 | Copyright © October 2016

Aditya K. Gupta MD PhD FRCPC a,b and Andrew Korotzer PhDc

aUniversity of Toronto, Toronto, Canada bMediprobe Research Inc., London, Canada cValeant Pharmaceuticals North America LLC, Bridgewater, NJ

Abstract
BACKGROUND: Although a completely normal nail would be the ideal outcome when treating onychomycosis, this is not always achievable and long treatment courses or patient expectations can impact patient adherence. METHODS: We analyzed cure rates from a number of subpopulations derived from the two pivotal phase III studies with efinaconazole topical solution (10%) to provide some insights into clinically meaningful treatment outcomes and support for effective long-term management programs. RESULTS: Efinaconazole affords greater efficacy in milder disease, female patients, and those patients whose disease is relatively recent and confined to the great toenail, following 48 weeks’ treatment. With longer treatment courses, similar results may be achieved in other subpopulations. Clinically meaningful results (a 40% improvement in the involvement of the diseased nail) were achieved with efinaconazole within six months in half the patients treated, and in over 90% of patients by study end. A greater proportion of female patients achieved clinically meaningful results at six months, although treatment success did not seem to be influenced by baseline disease severity. CONCLUSIONS: The majority of patients treated with efinaconazole could expect to see clinically meaningful results within six months.

J Drugs Dermatol. 2016;15(10):1260-1266.

INTRODUCTION

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