Long-Term Follow-up of Onychomycosis Patients Treated With Efinaconazole
December 2017 | Volume 16 | Issue 12 | Original Article | 1269 | Copyright © December 2017
Richard A. Pollak DPM and Carla Ilie BS
Endeavor Clinical Trials, San Antonio, TX
Abstract
Background: Onychomycosis is a common disease that remains difficult to treat despite the introduction of new topical agents. Clinical trials on efinaconazole and tavaborole included 48 weeks’ daily treatment regimens with a 4-week follow-up. It has been suggested that either a longer treatment regimen or longer follow-up would lead to even better results, primarily due to the time taken for the diseased nail to grow out, especially in those patients with more severe disease.
OBJECTIVE: To investigate the impact of a longer follow-up period on the efficacy of efinaconazole 10% topical solution in patients with moderate-to-severe onychomycosis.
METHODS: Single center, open-labeled study in 23 subjects aged 18-80 years with a clinical and mycological diagnosis of moderate-to-severe dermatophyte toenail onychomycosis (40-75% clinical involvement). Subjects were treated with efinaconazole 10% solution, once-daily for 48 weeks, with two 12-week post-treatment follow-ups (at week 60 and 72). Primary efficacy endpoint was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture). Secondary endpoints included mycologic cure rates and treatment success (defined as those patients who had at least a 50% improvement in affected toenail from baseline).
RESULTS: Twenty-two subjects completed the study. Mean baseline age 59.4 years (range, 37-77), predominance of male subjects (73.9%). Median baseline severity 50% affected target toenail. At week 72, two subjects were complete cures and 56.5% of subjects achieved treatment success. There were no complete cures at week 48, but 39.1% achieved treatment success. Mycologic cure rates were 91.3% at week 48. Median percent affected target toenail reduced to 40%, and further to 25% (week 48 and 72, respectively). Treatment was well tolerated, with no adverse events related to medication.
CONCLUSIONS: This single-center phase 4 study supports previous data showing good efficacy and tolerability of efinaconazole in moderately severe onychomycosis. Continued reduction in disease severity post-treatment suggest that a longer follow-up of patients treated with efinaconazole would afford better efficacy results, as indicated by greater treatment success, and increase in number of subjects who became complete cures.
J Drugs Dermatol. 2017;16(12):1269-1273.
INTRODUCTION
Efinaconazole 10% topical solution has been studied extensively for the treatment of mild-to-moderate toenail onychomycosis.1-8 The clinical results from two large phase 3 studies, and a number of post hoc analyses have already been published.1,2 Pooled complete cure rates of 18.5% and mycologic cure rates of 56.3% were demonstrated at week 52, compared with 4.7% and 16.6% with vehicle (observed case, both P less than 0.001).2It has been suggested that these complete cure rates may underestimate the true clinical value of efinaconazole, given that toenails require up to 78 weeks to grow out fully.1,2, 9, 10 The number of participants in the phase 3 studies who demonstrate ≤10% affected nail involvement at week 48 (44.9%, observed case), and at the 4-week follow-up (47.2%) are indicative that longer treatment periods or follow-up could result in higher cure rates.2Here we investigate the impact of a longer follow-up period on the efficacy and tolerability of efinaconazole 10% topical solution in patients with moderately severe onychomycosis.
METHODS
Study DesignA phase 4, single center, open-labeled study in 23 subjects aged 18-80 years with a clinical and mycological diagnosis of moderate-to-severe dermatophyte toenail onychomycosis (40-75% clinical involvement), including positive potassium hydroxide (KOH) microscopy results and dermatophyte culture. Subjects were also required to have no lunula, proximal nail, or nail matrix involvement, and have approximately 3mm of clear (unaffected) toenail proximally on the target affected great toenail at screening and baseline.Main exclusion criteria included subjects with severe dermatophytoma, streaks, or exclusively lateral edge involvement in the target great toenail, or toenail plate thickness of greater than 3 mm; subjects with psoriasis or lichen planus or yellow nail syndrome, or anatomic abnormalities of the target toenail or any other conditions that in the investigator’s judgment may interfere with efficacy assessment; females planning on become pregnant or who were pregnant; subjects with a history
