Is Severity of Disease a Prognostic Factor for Cure Following Treatment of Onychomycosis?
February 2018 | Volume 17 | Issue 2 | Original Article | 175 | Copyright © February 2018
Boni E. Elewski MD,a Wendy Cantrell DNP CRNP,a and Tina Lin PharmDb
aUniversity of Alabama at Birmingham School of Medicine, Birmingham, AL bValeant Pharmaceuticals, Bridgewater, NJ
BACKGROUND: Onychomycosis is a common disease that remains a difficult disorder to treat despite the introduction of new topical agents; and not all patients are cured. Clinical experience leads us to suggest a number of host-related factors can affect the chance of cure, but studies supporting these observations are currently lacking. Although many studies, particularly on topical agents, rely on severity classification when selecting patients for inclusion, a pilot study was unable to demonstrate any prognostic value of the extension of nail involvement. In addition, no universal severity classification exists, and most studies do not report prognostic factors.
OBJECTIVE: To investigate the efficacy of efinaconazole topical solution, 10% in patients with mild-to-moderate onychomycosis and determine the impact of baseline severity on treatment outcome.
METHODS: Post hoc pooled analysis of two identical, multicenter, randomized, double-blind, vehicle-controlled studies in 1655 patients aged 18-70 years with a clinical and mycological diagnosis of mild-to-moderate dermatophyte toenail onychomycosis (20-50% clinical involvement). Patients were randomized (3:1) to efinaconazole 10% solution or vehicle, once-daily for 48 weeks, with 4-week post treatment follow-up. Efficacy criteria included clear nail (0% target nail plate involvement), almost clear nail (≤5% target nail plate involvement), and clinical treatment success (≤10% target nail plate involvement) at week 52. For the post hoc analysis, patients were classified as mild (20%-29% nail involvement), moderate (30%-39%), and moderately severe (40%-50%) at baseline.
RESULTS: Overall, 25%, 23%, and 52% of patients had mild, moderate, or moderately severe disease at baseline. Baseline nail involvement did not appear to predict treatment outcomes. The proportion of patients with mild disease who had a clear nail progressively reduced by week 36 (58%) and week 48 (41%), and even further by week 52 (37%). Of the 237 patients treated with efinaconazole who were ‘clear’ at week 52, 37%, 24%, and 39% had mild, moderate or moderately severe disease respectively at baseline. The majority of patients (N=634) saw at least a 50% improvement in their target toenail by week 52. Almost half of these patients (N=312, 49.2%) were moderately severe at baseline.
CONCLUSIONS: This post hoc analysis supports previous data showing good efficacy of efinaconazole in mild onychomycosis. The relative contribution to overall efficacy results at week 52 of patients with moderate or moderately severe disease was unexpected for a topical therapy, and warrants further study, especially as they represent the majority of patients enrolled in the two studies. It is possible that comparable efficacy can be achieved in these more severe patients with longer treatment courses, or follow-up.
J Drugs Dermatol. 2018;17(2):175-178.
Onychomycosis is a common problem in dermatology and podiatry practice that can result in significant morbidity.1,2 It can be a challenge to treat successfully, and while experience leads us to suggest a number of host-related factors might affect the chance of clinical cure, studies supporting these observations are currently lacking. Intuitively, in patients with more severe disease treatment success may be more difficult. A pilot study of patients treated with continuous or intermittent terbinafine suggested that the number of toenails involved, percentage of nail involvement, duration of infection, type of onychomycosis, and the presence of spikes had no prognostic value in determining clinical cure (a nail without any clinical signs of onychomycosis).3 On the other hand, patients with matrix involvement, slow nail growth, a history of prior infection, men and older patients, and those with dermatophytoma were less likely to reach clinical cure.3 A number of post hoc analyses have been published on the use of efinaconazole topical solution, 10% in the treatment of mild-to-moderate onychomycosis that allow us to further investigate potential prognostic factors. These data have also shown that gender impacts outcome, with significantly greater efficacy in female patients.4 It is less clear why male patients would do less well; they may present with more severe disease, thicker toenails, be less compliant, or have slower growing/longer toenails whereby a longer treatment duration or follow-up would be necessary to judge. Age did not seem to be a prognostic factor in these post hoc analyses. Although there was a trend to younger patients (<40 years of age) doing