Original Research

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

Cutis. 2015 September;96(3):197-201

References

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Results

The 2 studies included a total of 1275 (77.2%) male and 376 (22.8%) female participants with mild to moderate onychomycosis (intention-to-treat population). Pooled results are provided in this analysis.

At baseline, the mean area of target toenail involvement among male and female participants in the efinaconazole treatment group was 36.7% and 35.6%, respectively, compared to 36.4% and 37.9%, respectively, in the vehicle group. The mean number of affected nontarget toenails was 2.8 and 2.7 among male and female participants, respectively, in the efinaconazole group compared to 2.9 and 2.4, respectively, in the vehicle group (Table 1).

Female participants tended to be somewhat more compliant with treatment than male participants at study end. At week 52, 93.0% and 93.4% of female participants in the efinaconazole and vehicle groups, respectively, were considered compliant with treatment compared to 91.1% and 88.6% of male participants, respectively (Table 1).

Primary Efficacy End Point (Observed Case)

At  week 52, 15.8% of male and 27.1% of female participants in the efinaconazole treatment group had a complete cure compared to 4.2% and 6.3%, respectively, of those in the vehicle group (both P<.001). Efinaconazole topical solution 10% was significantly more effective than vehicle from week 48 (P<.001 male and P=.004 female).

The differences in complete cure rates reported for male (15.8%) and female (27.1%) participants treated with efinaconazole topical solution 10% were significant at week 52 (P=.001)(Figure 1).

^{Figure 1. Proportion of male and female participants treated with once-daily application of efinaconazole topical solution 10% who achieved complete cure from weeks 12 to 52 (observed case; intention-to-treat population; pooled data).}

^{Figure 2. Treatment success (defined as ≤10% clinical involvement of the target toenail) at week 52. Comparison of results with efinaconazole topical solution 10% and vehicle (observed case; intention-to-treat population; pooled data).}

Secondary and Supportive Efficacy End Points (Observed Case)

At week 52, 53.7% of male participants and 64.8% of female participants in the efinaconazole group achieved mycologic cure  compared to 14.8% and 22.5%, respectively, of those in the vehicle group (both P<.001). Mycologic cure in the efinaconazole group versus the vehicle group became statistically significant at week 12 in male participants (P=.002) and at week 24 in female participants (P<.001).

At week 52, more male and female participants in the efinaconazole group (24.9% and 36.8%, respectively) achieved complete or almost complete  cure compared to those in the vehicle group (6.8% and 11.3%, respectively), and 43.5% and 59.1% of male and female participants, respectively, were considered treatment successes (≤10% clinical involvement of the target toenail) compared to 15.5% and 26.8%, respectively, in the vehicle group (all P<.001)(Figure 2).

Treatment satisfaction scores were higher among female participants. At week 52, the mean QOL assessment score among female participants in the efinaconazole group was 77.2 compared to 70.3 among male participants in the same group (43.0 and 41.2, respectively, in the vehicle group). All QOL assessment scores were lower (ie, worse) in female onychomycosis participants at baseline. Improvements in all QOL scores were much greater in female participants at week 52 (Table 2).

The total number of efinaconazole applications was similar among male and female participants (315.1 vs 316.7). The mean amount of efina- conazole applied was greater in male participants  (50.4 g vs 45.6 g), and overall compliance rates, though similar, were slightly higher in females compared to males (efinaconazole only)(93.0%  vs 91.1%).

Safety

Overall, AE rates for efinaconazole were similar to those reported for vehicle (65.3% vs 59.8%).¹⁶ Slightly more female participants reported 1 or more AE than males (71.3% vs 63.5%). Adverse events were generally mild (50.0% in females; 53.7% in males) or moderate (46.7% in females; 41.8% in males) in severity, were not related to the study drug (89.9% in females; 93.1% in males), and resolved without sequelae. The rate of discontinuation from AEs was low (2.8% in females; 2.5% in males).

Comment

Efinaconazole topical solution 10% was significantly more effective than vehicle in both male and female participants with mild to moderate onychomycosis. It appears to be especially effective in female participants, with more than 27% of female participants achieving complete cure at week 52, and nearly 37% of female participants achieving complete or almost complete cure at week 52.

Mycologic cure is the only consistently defined efficacy parameter reported in toenail onychomycosis studies.¹⁸ It often is considered the main treatment goal, with complete cure occurring somewhat later as the nails grow out.¹⁹ Indeed, in this subgroup analysis the differences seen between the active and vehicle groups correlated well with the cure rates seen at week 52. Interestingly, significantly better mycologic cure rates (P=.002, active vs vehicle) were seen as early as week 12 in the male subgroup.