Are topical and device-based therapies safe and effective in the treatment of toenail onychomycosis?
Topical antifungal drugs, including efinaconazole 10% solution (Jublia), tavaborole 5% solution (Kerydin), and ciclopirox 8% lacquer and hydrolacquer, are beneficial in treating mild to moderate toenail onychomycosis.1,2 Potential adverse effects are mild and include dermatitis and vesicles.1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Onychomycosis, a fungal infection of the nail caused by dermatophytes, nondermatophyte molds, and yeasts, is the most common nail disorder encountered in primary care.1,3 Aside from its cosmetic impact, toenail onychomycosis may cause pain and discomfort.1 Oral antifungal medications are considered the most effective treatment; however, they are associated with drug interactions and systemic adverse effects.1 The authors of this review sought to determine the safety and effectiveness of topical and device-based therapies to treat toenail onychomycosis.
This Cochrane review included 56 randomized controlled trials (published between 1993 and 2019) involving 12,501 participants.1 The primary outcomes were complete cure rate (defined as mycologic cure and resolution of all clinical symptoms) and treatment-related adverse effects. Secondary outcomes at follow-up included mycologic cure rate (negative mycologic testing) and clinical cure rate (0% nail plate involvement). Ultimately, 12 studies involving 4,269 participants were included in the quantitative meta-analysis.1 Most studies addressed mild to moderate onychomycosis without matrix involvement and with more than one toenail affected. Participants were 27 to 68 years of age, on average, with a treatment duration of 36 or 48 weeks, and clinical outcomes were measured up to four weeks after treatment completion.
High-quality evidence demonstrated that efinaconazole 10% solution was superior to placebo at achieving clinical cure (relative risk [RR] = 3.07; 95% CI, 2.08 to 4.53; two studies, 1,655 participants) and complete cure (RR = 3.54; 95% CI, 2.24 to 5.60; three studies, 1,716 participants). Moderate-quality evidence demonstrated that efinaconazole 10% solution produced mycologic cure (RR = 2.31; 95% CI, 1.08 to 4.94; three studies, 1,716 participants).
In two studies involving 1,198 participants, tavaborole 5% solution was superior to placebo at achieving mycologic cure (RR = 3.40; 95% CI, 2.34 to 4.93; high-quality evidence) and complete cure (RR = 7.40; 95% CI, 2.71 to 20.24; moderate-quality evidence). Finally, ciclopirox 8% lacquer was superior to placebo at achieving mycologic cure (RR = 3.15; 95% CI, 1.93 to 5.12; two studies, 460 participants; moderate-quality evidence) and complete cure (RR = 9.29; 95% CI, 1.72 to 50.14; two studies, 460 participants; low-quality evidence). Additional studies reviewed by the authors were very low quality and did not demonstrate effectiveness for 1064-nm Nd:YAG (neodymium:yttrium-aluminum-garnet) laser (three studies) or luliconazole 1% solution (Luzu; one study).1
When compared with ciclopirox 8% lacquer and amorolfine 5% lacquer, ciclopirox 8% hydrolacquer was more effective at achieving complete cure (RR = 2.43; 95% CI, 1.32 to 4.48; two studies, 490 participants; moderate-quality evidence). However, there was no difference between these treatments in mycologic cure or risk of adverse effects, including erythema, rash, and burning.1
Adverse effects such as dermatitis and vesicles were associated with use of efinaconazole (RR = 1.10; 95% CI, 1.01 to 1.20; three studies, 1,701 participants; high-quality evidence), and adverse effects at the application site occurred in studies of tavaborole (RR = 3.82; 95% CI, 1.65 to 8.85; two studies, 1,186 participants; moderate-quality evidence). Use of ciclopirox 8% lacquer did not seem to increase the risk of rash or nail alteration.1
Current clinical practice guidelines recommend using oral antifungal agents as first-line treatment for onychomycosis; however, this may not be feasible for patients with limited access to care, potential drug interactions, contraindications to oral therapy, or a preference for topical treatment.4,5 Of note, oral terbinafine (Lamisil; $8 to $72 for 30 tablets) costs the same as or less than topical agents (e.g., ciclopirox 8% lacquer, which ranges from $16 to $45 per bottle).6
The practice recommendations in this activity are available at http://www.cochrane.org/CD012093.
This article reflects the opinions of the authors alone and does not reflect the opinion of the Department of the Army, the Department of the Air Force, the Department of the Navy, the Defense Health Agency, the Department of Defense, or the U.S. government.