Baseline Nail Thickness and Great Toenail Involvement Are Associated With Poor Response to Topical Antifungal Therapy for Onychomycosis: A Lesion-Level Generalized Estimating Equations Analysis.

Topical antifungals are widely used for onychomycosis; however, lesion-level morphological predictors of response have rarely been quantified while accounting for within-patient correlation. We retrospectively studied patients with onychomycosis treated with topical luliconazole 5% nail solution or efinaconazole 10% solution between 2017 and 2021. Eighty lesions from 66 patients were identified. Treatment response was evaluated using lesion-level generalized estimating equations (GEE) clustered by patient ID with an exchangeable working correlation structure and robust (sandwich) standard errors. Improvement rate (continuous) was analyzed using a linear GEE, and complete cure (yes/no) using a logistic GEE. Great toenail involvement was consistently associated with poor response, showing a lower improvement rate, β = -0.461 (standard error [SE] = 0.145; p = 0.0015), and markedly lower odds of complete cure, odds ratio (OR) 0.07 (95% confidence interval [CI] 0.01-0.37; p = 0.002). Greater baseline nail thickness was associated with lower odds of complete cure, OR 0.17 (95% CI 0.07-0.42; p < 0.001), although it was not significantly associated with improvement rate, β = -0.089 (SE = 0.058; p = 0.125). Use of luliconazole 5% nail solution (vs. efinaconazole 10% solution) was associated with a lower improvement rate, β = -0.310 (SE = 0.154; p = 0.044) and lower odds of complete cure, OR 0.07 (95% CI 0.01-0.60; p = 0.015); these associations should be interpreted cautiously because treatment allocation was not randomized. Sensitivity analyses using a linear mixed-effects model showed consistent directions of effect. Great toenail involvement appears to be a robust predictor of poor response to topical therapy, and increased nail thickness may particularly hinder achieving complete cure; these findings warrant cautious interpretation given the retrospective, non-randomized design.