Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects

March 2018 | Volume 17 | Issue 3 | Original Article | 347 | Copyright © 2018

Raza Aly PhD,a† Tate Winter PhD,b† Steve Hall PharmD,b Tracey Vlahovic DPMc

aUniversity of California Medical Center, San Francisco, CA bSandoz, A Novartis Division, Princeton, NJ cTemple University School of Podiatric Medicine, Philadelphia, PA †These authors contributed equally to this work

Abstract

Dermatophytoma is a little-known, difficult to treat fungal infection that complicates onychomycosis. First described by Roberts and Evans in the late 1990’s, dermatophytoma presents as a dense concentration of fungal hyphae within or under the nail plate and is generally white or yellow/brown in color, and linear (streaks) or round (patches) in shape; primary etiologic organisms are dermatophytes. Oral antifungals have limited success in treating dermatophytoma owing to difficulties accessing and penetrating what is hypothesized to be a fungal biofilm. In this respect, dermatophytoma is generally treated with a combination therapy approach, often including both surgical and pharmacologic intervention for improved outcomes. A post-hoc assessment of Phase II tavaborole onychomycosis studies was conducted in order to assess the prevalence of dermatophytoma and outcomes in patients treated with topical tavaborole. Of the 366 subjects enrolled in the Phase II onychomycosis studies, we identified 102 cases of dermatophytoma; 21 of 86 (24.4%) subjects treated with tavaborole were able to achieve complete resolution of dermatophytoma by day 180, while no subjects on vehicle obtained resolution. Similarly, 23 of 86 subjects (26.7%) treated with tavaborole solution had complete resolution of dermatophytoma by day 360, while only 1 of 16 subjects (6.3%) on vehicle obtained resolution. Moreover, 13 of 19 subjects (68.4%) treated with tavaborole solution were able to sustain resolution, while only 6 of 19 (31.6%) had reoccurrence, of dermatophytoma during the 180-day washout period (day 360). We present 5 cases of dermatophytoma identified in Phase II trials that responded in a positive manner following treatment with tavaborole solution for onychomycosis of the great toenail. Although not representative of all subject outcomes, these findings provide insight into the use of topical tavaborole for dermatophytoma, a condition previously thought to respond only to oral or combination therapy.

J Drugs Dermatol. 2018;17(3):347-354.

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Introduction

Dermatophytoma, characterized by a dense round or linear mass of fungal hyphae within the nail unit, poses a significant therapeutic challenge for both oral and classical topical therapies owing to difficulties achieving adequate drug penetration within the fungal mass.1,2 Similar to pulmonary aspergilloma (ie, a fungal mass in the lung), dermatophytoma is frequently treated with broad-spectrum oral antifungals with limited success. Dermatophytoma thus often requires surgical excision along with pharmacologic intervention for improved clearance.1,3,4 The reported prevalence of dermatophytoma in the literature in patients with onychomycosis varies widely, ranging from 0.9% to 9.0%5–8; these numbers are likely underestimated due to the lack of overall diagnostic awareness by treating practitioners, as well as their widespread exclusion from Phase III clinical trials, owing to their poor response to therapy.7 Efforts to elucidate the resistance of dermatophytoma, as well as the recalcitrance of onychomycosis, have shown that Trichophyton rubrum, the main causative organism of onychomycosis, and other invasive non-dermatophytes (eg, Candida albicans), have innate resistance mechanisms which limit drug penetration at the site of infection, thereby improving fungal viability.1,2,7,9 Fungal resistance mechanisms include the ability to switch strains, upregulate multidrug efflux pumps, and form polysaccharide-rich biofilms.2,9–11As previously mentioned, a major hurdle in the treatment of dermatophytoma is achieving therapeutic drug levels at or within the fungal infection. In this respect, practitioners have previously taken a more aggressive treatment approach when dealing with dermatophytoma, and other clinical features of moderate to severe onychomycosis (eg, substantial lateral-, matrix-, >50% nail plate-involvement etc),12 including combination therapy with oral, topical, and/or chemical/surgical methods (eg, urea 40%, nail avulsion, debridement, etc).4,7,8,13–15 It is suggested that these polymodal therapeutic approaches help to reduce fungal burden and enhance drug delivery to

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