Topical and device‐based treatments for fungal infections of the toenails

Review question

We reviewed evidence about the effect of topical and device‐based treatments for fungal infections of the toenails (toenail onychomycosis) when compared against each other, placebo (an identical but inactive treatment), vehicle (inactive ingredients that help deliver an active treatment), or no treatment. We assessed adults, whose infection was diagnosed based on studying nail samples.

Background

Toenail onychomycosis causes pain, discomfort, and disfigurement. Topical and device‐based treatments can have less likelihood of drug interactions or side effects than oral drugs. Antifungal medications are either fungistatic (inhibiting fungal growth) or fungicidal (killing fungal pathogens). The shared goal of devices (e.g. laser, photodynamic therapy) is fungus destruction.

Study characteristics

In searches up to May 2019, we found 56 studies including 12,501 men or women (average age: 27 to 68 years) who had mainly mild‐to‐moderate toenail onychomycosis. Onychomycosis duration was under‐reported, but varied from months to years. Approximately 63% of the studies assessed onychomycosis caused by dermatophytes (fungi). Most studies lasted 48 to 52 weeks and were conducted in an outpatient setting. The studies used either device‐based or topical treatments, including lacquers and creams, alone or in combination, compared to each other, to no treatment, to vehicle, or to placebo.

Key results

For the following key results, treatment lasted 36 or 48 weeks, and outcomes were measured at 40 to 52 weeks (side effects were measured throughout the study).

Compared to vehicle (no treatment), efinaconazole 10% topical solution is better at achieving complete cure (i.e. normal‐looking nail coupled with fungus elimination determined using laboratory methods) (high‐quality evidence). Tavaborole 5% solution (when compared to vehicle) and P‐3051 (ciclopirox 8% hydrolacquer) (when compared to two other treatments: ciclopirox 8% lacquer or amorolfine 5%) are probably better at achieving this outcome (both moderate‐quality evidence). Ciclopirox 8% lacquer may lead to higher complete cure rates than vehicle, but rates are low (not all patients can be expected to achieve complete cure) (low‐quality evidence).

Ciclopirox 8% lacquer and efinaconazole 10% are probably more effective at eliminating the fungus (mycological cure) than vehicle, but for P‐3051 (ciclopirox 8% hydrolacquer) there is probably little or no difference compared to the two comparator treatments (all moderate‐quality evidence). Tavaborole 5% improves mycological cure compared to vehicle (high‐quality evidence).

We found no evidence of a difference in side effects, including redness, rash, and burning, between P‐3051 (ciclopirox 8% hydrolacquer) and the two other treatments (low‐quality evidence), and ciclopirox 8% lacquer may increase side effects, including application‐site reactions, rashes, and changes in the nail compared with vehicle, although treatment effects vary, so it is possible that it may actually make little or no difference (low‐quality evidence). Compared to vehicle, participants were slightly more likely to experience side effects (commonly dermatitis and fluid‐filled sacs) with efinaconazole 10% (high‐quality evidence) and probably more likely to experience side effects with tavaborole 5% (commonly, application‐site reactions, such as dermatitis, redness, and pain) (moderate‐quality evidence).

We are uncertain of the effect of luliconazole 5% on complete cure when compared to vehicle (very low‐quality evidence); there may be little or no difference between these groups in side effects (dry skin, eczema, and thickening of the skin were commonly reported, but improved after stopping treatment), and luliconazole 5% solution might increase mycological cure; however, the effects of this treatment vary, so it is possible that it may actually make little or no difference to mycological cure (both low‐quality evidence).

Three studies compared laser to no treatment or sham treatment, and there may be little or no difference in mycological cure (low‐quality evidence). Complete cure was not measured, and we are uncertain if there is a difference in side effects between groups (very low‐quality evidence).

Efinaconazole 10% solution is more effective in achieving clinical cure than vehicle (high‐quality evidence); none of the other key comparisons measured this outcome.

Quality of the evidence

We base our conclusions on varied evidence quality. For complete cure, mycological cure, and side effects, quality ranged from low to high, with very low‐quality evidence found for three key results.

Many studies were small, had design issues, and did not directly compare therapies. No studies reported quality of life.