Original Research

Evaluation of Gender as a Clinically Relevant Outcome Variable in the Treatment of Onychomycosis With Efinaconazole Topical Solution 10%

Author and Disclosure Information

Although there are limited data available on gender as an outcome variable in the treatment of onychomycosis, differences in disease prevalence and impact in males versus females have been observed. This article provides a gender subgroup analysis based on results from recent studies evaluating the efficacy, safety, and tolerability of efinaconazole topical solution 10% in the treatment of onychomycosis. Data were collected from two 52-week, prospective, multicenter, randomized, double-blind studies of patients 
(age range, 18–70 years) randomized to receive either efinaconazole topical solution 10% or vehicle for treatment of onychomycosis. Results from this analysis indicated that once-daily application of efinaconazole topical solution 10% may provide a useful topical option for treatment of mild to moderate toenail onychomycosis, especially in female patients.

Practice Points

  • Men, particularly as they age, are more likely to develop onychomycosis.
  • Treatment adherence may be a bigger issue among male patients.
  • Onychomycosis in males may be more difficult to treat for a variety of reasons.


 

References

Onychomycosis is the most common nail disease 
in adults, representing up to 50% of all nail disorders, and is nearly always associated with tinea pedis.1,2 Moreover, toenail onychomycosis frequently involves several nails3 and can be more challenging to treat because of the slow growth rate of nails and the difficult delivery of antifungal agents to the nail bed.3,4

The most prevalent predisposing risk factor for developing onychomycosis is advanced age, with a reported prevalence of 18.2% in patients aged 60 to 79 years compared to 0.7% in patients younger than 19 years.2 Men are up to 3 times more likely to develop onychomycosis than women, though the reasons for this gender difference are less clear.2,5 It has been hypothesized that occupational factors may play a role,2 with increased use of occlusive footwear and more frequent nail injuries contributing to a higher incidence of onychomycosis in males.6

Differences in hormone levels associated with gender also may result in different capacities to inhibit the growth of dermatophytes.2 The risk for developing onychomycosis increases with age at a similar rate in both genders.7

Although onychomycosis is more common in men, the disease has been shown to have a greater impact on quality of life (QOL) in women. Studies have shown that onychomycosis was more likely to cause embarrassment in women than in men 
(83% vs 71%; N=258), and women with onychomycosis felt severely embarrassed more often than men (44% vs 26%; N=258).8,9 Additionally, one study (N=43,593) showed statistically significant differences associated with gender among onychomycosis patients who reported experiencing pain 
(33.7% of women vs 26.7% of men; P<.001), discomfort in walking (43.1% vs 36.4%; P<.001), and embarrassment (28.8% vs 25.1%; P<.001).10 Severe cases of onychomycosis even appear to have a negative impact on patients’ intimate relationships, and lower self-esteem has been reported in female patients due to unsightly and contagious-looking nail plates.11,12 Socks and stockings frequently may be damaged due to the constant friction from diseased nails that are sharp and dystrophic.13,14 In one study, treatment satisfaction was related to improvement in nail condition; however, males tended to be more satisfied with the improvement than females. Females were significantly less satisfied than males based on QOL scores for discomfort in wearing shoes (61.5 vs 86.3; P=.001), restrictions in shoe options (59.0 vs 82.8; P=.001), and the need to conceal toenails (73.3 vs 89.3; P<.01).15

Numerous studies have assessed the effectiveness of antifungal drugs in treating onychomycosis; however, there are limited data available on the impact of gender on outcome variables. Results from 2 identical 52-week, prospective, multicenter, randomized, double-blind studies of a total of 1655 participants 
(age range, 18–70 years) assessing the safety and efficacy of efinaconazole topical solution 10% in the treatment of onychomycosis were reported in 2013.16 Here, a gender subgroup analysis for male and female participants with mild to moderate onychomycosis is presented.

Methods

Two 52-week, prospective, multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution 10% versus vehicle in 1655 participants aged 18 to 70 years with mild to moderate toenail onychomycosis. Participants who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1 ratio) to once-daily application of a blinded study drug on the toenails for 48 weeks, followed by a 4-week follow-up period.16

Efficacy Evaluation

The primary efficacy end point was complete cure, defined as 0% clinical involvement of target toenail and mycologic cure based on negative potassium hydroxide examination and negative fungal culture at week 52.16 Secondary and supportive efficacy end points included mycologic cure, treatment success (<10% clinical involvement of the target toenail), complete or almost complete cure (≤5% clinical involvement and mycologic cure), and change in QOL based on a self-administered QOL questionnaire. All secondary end points were assessed at week 52.16 All items in the QOL questionnaire were transferred to a 0 to 100 scale, with higher scores indicating better functioning.17

In both studies, treatment compliance was assessed through participant diaries that detailed all drug applications as well as the weight of returned product bottles. Participants were considered noncompliant if they missed more than 14 cumulative applications of the study drug in the 28 days leading up to the visit at week 48, if they missed more than 20% of the total number of expected study drug applications during the treatment period, and/or if they missed 28 or more consecutive applications of the study drug during the total treatment period.

Safety Evaluation

Safety assessments included monitoring and recording adverse events (AEs) until week 52.16

Pages

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