Efinaconazole Topical, 10% for the Treatment of Toenail Onychomycosis in Patients With Diabetes
October 2014 | Volume 13 | Issue 10 | Original Article | 1186 | Copyright © October 2014
Tracey C. Vlahovic DPMa and Warren S. Joseph DPM FIDSAb
aTemple University School of Podiatric Medicine, Philadelphia, PA
bRoxborough Memorial Hospital, Philadelphia, PA
OBJECTIVE: To evaluate efficacy, safety, and tolerability efinaconazole topical solution, 10% in diabetic patients with onychomycosis
METHODS: A post-hoc analysis of 112 patients, aged 29-70 years, randomized to receive efinaconazole topical solution, 10% or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52.
RESULTS: Mycologic cure rates (OC) were significantly greater with efinaconazole (56.5% and 56.3% in diabetic and non-diabetic patients respectively) compared to vehicle (P
=0.016 and P
<0.001, respectively). The primary end point, complete cure, was also greater for efinaconazole (13.0% and 18.8%, respectively vs 3.7% and 4.7%). Treatment success (percent affected target toenail ≤10%) for efinaconazole was 40.8% and 47.7%, respectively vs 18.5% and 18.2% with vehicle. There was no statistically significant difference between the diabetic and non-diabetic populations for any efficacy endpoint. Adverse events associated with efinaconazole were local site reactions and clinically similar to vehicle.
CONCLUSIONS: Once daily efinaconazole topical solution, 10% may provide a useful topical option in the treatment of diabetic patients with onychomycosis. J Drugs Dermatol.
Approximately one in three people with diabetes are afflicted with onychomycosis,1 and diabetic individuals suffer from a much higher incidence of onychomycosis than those without; especially older patients, males, and those with severe nail changes.
Onychomycosis is an important cause of morbidity in diabetic patients, increasing their risks for limb amputation, and both local and systemic secondary bacterial infections.2 Onychomycosis may result in foot ulceration as a result of a thick, sharp, brittle piece of nail piercing the skin, peripheral neuropathy resulting in altered sensation, trauma, decreased resistance to infection, or vascular disease causing poor tissue oxygenation.3-5 Injury creates a portal for pathogen entry, promoting the development of further complications and outcomes including cellulitis, osteomyelitis, gangrene, and lower limb amputation. Evidence exists to suggest that patients with cellulitis, osteomyelitis, and gangrene are also likely to have onychomycosis.1,6-9 Studies also indicate a higher association between the rate of foot ulceration and gangrene in patients with diabetes and onychomycosis compared to diabetic patients without onychomycosis.5,10 Effective and safe treatment of onychomycosis is therefore especially important for patients with diabetes as it may prevent ulcer formation and secondary complications.11
Although numerous studies have assessed the effectiveness of antifungal drugs in treating onychomycosis, most exclude patients with diabetes and examine otherwise healthy individuals. While these studies are useful, results cannot necessarily be extrapolated to patients with diabetes. Firstly, diabetic patients often take concomitant medications, and many drugs have the potential to interact with antifungal medication influencing the choice of ideal therapy for this important group.12 Secondly, people with diabetes tend to be resistant to treatment as high blood glucose levels and poor foot care foster fungal growth.13 For example, the presence of onychomycosis in diabetic patients was significantly associated with not washing of feet every day.14 Long-term control of glycemia to prevent chronic complications and obesity is essential in preventing onychomycosis and its potential complications.15
A recent systematic review16 identified six studies (N=13 to 89) examining the safety and/or efficacy of treatment interventions for onychomycosis in people with diabetes. Two studies were randomized controlled trials (N=52 and 70),17,18 the remaining four were case series.19-22
It is often suggested that patients with diabetes are more resistant to antifungal treatment interventions than non-diabetic