Abstract and Introduction
Abstract
Efinaconazole 10% nail solution is a novel topical antifungal drug for the treatment of onychomycosis. Two Phase III trials were completed using efinaconazole 10% nail solution, where 17.8% and 15.2% of patients achieved complete cure, and 55.2% and 53.4% achieved mycological cure. Several post hoc analyses were carried out using data from Phase III trials to determine the efficacy of efinaconazole with respect to disease duration, disease progression, and comorbidities of diabetes or tinea pedis with onychomycosis. Efinaconazole produced higher efficacy rates with patients presenting onychomycosis in a small portion of the toenail (≤25%) for a shorter duration of time (<1 year and 1–5 years). When patients presenting with both onychomycosis and tinea pedis underwent concurrent treatment, efficacy of efinaconazole increased from 16.1% to 29.4%, suggesting combination therapy improved results. Most interestingly, there was no difference in efinaconazole efficacy between diabetic and non-diabetic groups, indicating efinaconazole could be a safe and effective form of treatment for diabetics. Overall, efinaconazole 10% nail solution shows potential as an antifungal therapy for the treatment of onychomycosis.
Introduction
Onychomycosis is a fungal infection of the nail unit caused by dermatophytes, yeasts, and nondermatophyte molds.[1] Onychomycosis affects toenails more frequently than fingernails and accounts for 50% of nail disease.[2,3] Although this infection can be perceived as merely a cosmetic issue of thickening and discoloration of the nail plate, onychomycosis can result in numerous side effects that can impede the use of shoes and make walking difficult in general, leading to decreased quality of life.[4,5] Additional risks include bacterial infections, foot ulcers, and gangrene.[6] As a commonly occurring disease, it affects 2–13% of the general population, with prevalence of up to 50% in patients aged 70 years or higher.[7] Along with advanced age, there are several other risk factors including diabetes, peripheral arterial disease, immunosuppression, and other pre-existing nail diseases like psoriasis.[8] Due to an increased chance of comorbidity with onychomycosis, most recent investigational interests have focused on topical antifungals, which have a lower risk of adverse effects and drug-drug interactions.
The goal of onychomycosis treatment is restoring the nail to a normal appearance and complete eradication of fungus. This can be difficult to achieve as the nail plate acts as a barrier for topical treatments, and poor circulation in the elderly can prevent systemic treatments from reaching their target. Although some therapies can result in complete clinical and mycological cure, the rates are low (35–50%), and risk of relapse is high (10–53%).[9] Currently, there are five classes of drugs approved for the treatment of onychomycosis: allylamines, azoles, morpholines, hydroxypyridinones, and benzoxaboroles.[10,11] Historically, systemic therapies have been the most effective, with the oral allylamine terbinafine being the current gold standard with a complete cure rate of 38% and mycological cure rate of 74%.[12,13] The recommended dose of terbinafine for toenail onychomycosis is 250 mg daily for 12 weeks. Patients who are high risk for adverse effects from oral antifungals are prescribed topical agents. In the US there are three topical therapies approved for the treatment of onychomycosis: ciclopirox 8% nail solution, tavaborole 5% solution, and efinaconazole 10% solution. Given the challenges of transungual delivery, there is a need for novel topical antifungals that can increase penetrance, are potent, and carry minimal side effects.
Efinaconazole 10% solution is a novel topical antifungal of the azole class that was US FDA approved for the treatment of toenail onychomycosis in June 2014.[14] Efinaconazole has demonstrated a broad spectrum of activity against dermatophytes and yeasts in vitro,[15] and has uniquely low keratin affinity, allowing drug release from keratin and enhanced penetration through the nail plate compared to ciclopirox and amorolfine.[16] Due to the unique formulation of efinaconazole, both transungual and subungual routes of delivery are achieved as the drug penetrates through the nail plate into the underlying nail bed, as well as via spreading around and under the nail plate through the air gap to reach the fungal infection.[17,18] Recently, a human cadaver nail study demonstrated that efinaconazole is able to penetrate the nail even in the presence of nail polish,[19] which may be a potential advantage for patients concerned with hiding nail abnormalities while at the same time using a topical treatment. Efinaconazole works by inhibiting the synthesis of ergosterol, an essential structural component of fungal cell membranes.[20,21] Its inhibition results in a loss of cell membrane integrity, thus preventing fungal cell growth.[20,21]
Previously, two identical, randomized, double-blind, vehiclecontrolled Phase III studies were performed using 1655 patients with mild to moderate toenail onychomycosis.[22] The treatment course was once daily application of efinaconazole 10% nail solution to the affected toenail and underside, as well as surrounding skin, for 48 weeks followed by a 4 week washout period.23 At week 52, 17.8% and 15.2% of patients achieved complete cure, and 55.2% and 53.4% achieved mycological cure.[24] Interestingly, female patients demonstrated higher efficacies than males (27.1% vs 15.8%, respectively, P=0.001), where the only notable difference between genders were mean weight (73.3 kg and 90.2 kg).[22] Further subgroup analyses were completed using Phase III data to elucidate the differences in treatment efficacy in patients with concurrent tinea pedis or diabetes, as well as duration and severity of disease.[25–28]
Skin Therapy Letter. 2016;21(6):6-11. © 2016 SkinCareGuide.com
