Tavaborole in Difficult-to-Treat Onychomycosis Cases: A Post-hoc Assessment of Phase III Subjects
October 2017 | Volume 16 | Issue 10 | Original Article | 1016 | Copyright © October 2017
Raza Aly PhD,a Aditya K. Gupta MD PhD,b,c Tate Winter PhD,d Lee T. Zane MD,e Tracey Vlahovic DPMf
aDepartment of Dermatology, University of California Medical Center, San Francisco, CA bDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada cMediprobe Research Inc., London, Ontario, Canada dSandoz, A Novartis Division, Princeton, NJ eAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY fTemple University School of Podiatric Medicine, Philadelphia, PA
Toenail onychomycosis is a chronic fungal infection that often requires prolonged treatment in order to effectively manage pathogenic organisms and obtain a clear nail. Traditionally, certain clinical features of onychomycosis, including the presence of substantial lateral disease, focal fungal masses, yellow/brown streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment prognosis and have proven difficult-to-treat with oral or traditional topical therapies. Owing to the novel features of topical tavaborole, we sought to understand the potential utility of tavaborole in difficult-to-treat onychomycosis. A blinded, post-hoc assessment of Phase III trials was conducted, focusing on initial presentation, midpoint assessment (24 weeks), and final outcomes (52 weeks) in subjects identified as having difficult-to-treat onychomycosis and treated for 48 weeks with once-daily application of either tavaborole 5% solution or vehicle. Our post-hoc analysis identified 84 difficult-to-treat cases (tavaborole 5%; n=60; vehicle, n=24) in subjects with toenail onychomycosis due to Trichophyton rubrum or Trichophyton mentagrophytes. No subjects identified as difficult-to-treat and treated with vehicle achieved a complete cure, while 6 subjects treated with tavaborole 5% attained a completely clear nail and negative mycology. Similarly, 7 subjects treated with tavaborole 5% solution achieved an almost complete cure (≤10% involvement and negative mycology) while 1 subject on vehicle achieved an almost complete cure. We present a case series of 4 patients, of varying age and difficult-to-treat clinical features, which responded positively to tavaborole 5% solution. Three of the subjects achieved complete cure after being treated with tavaborole 5%, with one additional subject (an 88-year-old female) achieving an almost complete clear nail by treatment end. The outcomes presented here may not be reflective of patients that may present with these clinical characteristics. Additional investigations would be useful in order to assess the value of topical tavaborole 5% solution in difficult-to-treat clinical presentations of onychomycosis.
J Drugs Dermatol. 2017;16(10):1016-1021.
Onychomycosis is a chronic fungal infection of the nail unit primarily caused by the dermatophytes T. rubrum and T. mentagrophytes.1,2 The highly refactory nature of the disease is attributed to slower nail growth in aged persons, as well as re-establishment of the infection by co-existing tinea pedis (ie, athlete’s foot), therefore making recurrence prevalent.3,4 Several factors including nail thickness, degree of onycholysis, vascular sufficiency, etiologic organisms, co-morbidities, etc., also variably contribute to difficulty in successfully treating onychomycosis.3,5–7 lateral onychomycosis, longitudinal spike, dermatophytoma, and extensive onycholysis These features necessitate the careful selection of the proper antifungal agent. Oral antifungal therapies, including itraconazole and terbina ne, demonstrate relatively high complete cure (22-38%) and mycologic cure rates (54-70%) with good safety profiles, and are often prescribed in individuals with several affected nails and nail involvement greater than 50%.8 While generally safe, reports of severe adverse safety events (eg, drug-drug interactions (DDI)) with oral antifungals have led to label changes and the establishment of alternate dosing regimens (eg, intermittent) for improved safety.9,10 One of the most effective treatments for dermatophyte onychomycosis, is continuous administration of 250 mg/day over 16 weeks. A few small studies, however, have raised the possibility of an alternative regimen: pulsed administration of 500 mg/day for 1 week, every 4 weeks (over 16 weeks Despite favorable outcomes with oral antifungal therapies, there are certain clinical features of onychomycosis that make the disease especially dif cult-to-treat: substantial lateral disease (with onycholysis), dense fungal masses, fungal streaks, and severe infections (> 50% nail involvement).8,11 In contrast to oral antifungals, topical antifungals, such as ciclopirox, have excellent safety profiles, albeit lower complete cure (5.5 to 8.5%) and mycologic cure rates (29 to 36%), with