Long-term Efficacy and Safety of Once-daily Efinaconazole 10% Topical Solution (Jublia) for Dermatophyte Toenail Onychomycosis

An Interim Analysis

Aditya K. Gupta, MD, PhD; Elizabeth A. Cooper, BESc, HBSc

Disclosures

Skin Therapy Letter. 2021;26(1) 

In This Article

Abstract and Introduction

Abstract

Onychomycosis, a difficult-to-treat fungal nail infection, is more prevalent in the elderly. Efinaconazole 10% topical solution is a firstline therapy for onychomycosis, based on phase III trials of 12-month treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. This is the first efficacy and safety data for a 24-month duration of efinaconazole 10% topical solution treatment for onychomycosis. Enrolled patients (N = 101) with mild to moderate distal lateral subungual onychomycosis applied efinaconazole to all affected toenails once daily for 18–24 months. Efficacy and safety were evaluated at months 6, 12, 18, and 24 (M6, M12, M18, and M24). The study is ongoing; to date, 47 patients have completed to M24. Mycological cure (MC) was 60.0% at M12, increasing to 74.2% at M24; effective cure (MC and ≤10% clinical involvement of the target toenail) was 17.8% at M12, rising to 19.4% at M24. Mild to moderate application site reactions were the only efinaconazole-related adverse events in 8 patients (7.9%). Increased age, increased severity of onychomycosis, and the presence of mixed infections (dermatophyte plus non-dermatophyte moulds) may drive a need for longer treatment durations. Although the data are interim, there is a trend of increasing efficacy beyond M12 use, without increased safety risk, even in patients >70 years of age.

Introduction

Onychomycosis is a chronic fungal nail infection, occurring at an estimated prevalence of 8–14% in North America.[1–3] Onychomycosis, while mainly asymptomatic, can result in reduced quality of life (cosmetic issues, pain, difficulty walking) and significant health impacts, particularly in diabetic patients and those with poor peripheral circulation (secondary skin infections, ulceration, amputation).[4–16] Traditional treatments for toenail onychomycosis have included oral agents such as terbinafine and itraconazole.[17] Despite good efficacy, oral agents present the potential for a significant number of drug interactions and hepatotoxicity, which are particularly problematic for elderly patients most in need of onychomycosis treatment to maintain health and mobility.

Efinaconazole 10% topical solution (Jublia™) is approved for mild to moderate dermatophyte toenail onychomycosis.[18,19] Efinaconazole inhibits fungal lanosterol 14α-demethylase, with broad spectrum of action against dermatophytes, yeasts and non-dermatophyte moulds (NDMs).[20] Efinaconazole 10% solution has low surface tension, with low affinity to keratin in the nail plate,[21] and accumulates in the nail plate and nail bed to levels well above the minimum inhibitory concentration (MIC) of dermatophytes after continuous application for 28 days.[22] In phase III trials that led to the approval of efinaconazole 10% solution, the mycological (MC) and complete cure (CC) rates of 48 weeks of efinaconazole treatment were 53–55% and 15–18%, respectively, comparable to some traditional oral agents.[19,23–26] Efinaconazole has also been shown to be effective in onychomycosis patients with diabetes (CC 13%) and coexisting tinea pedis (CC 29.4%).[27]

Despite the promising results of efinaconazole in the phase III trials, more than half of the treated patients were left with visual signs of infection in the target toenail.[23,24] It is suspected that the 48-week (12-month) treatment period may be insufficient for complete nail outgrowth, as it is noted that nail growth rates are reduced in onychomycotic compared to healthy nails.[28–31] To investigate this possibility, we present interim results of a study to assess the safety and efficacy of treatment up to 24 months with efinaconazole for mild to moderate toenail distal lateral subungual onychomycosis (DLSO).

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