Putting the fun in fungi: toenail onychomycosis

Clinical question

How effective are treatments for mild to moderate adult toenail onychomycosis?

Bottom line

Up to 45% to 60% of patients taking oral treatments, 6% to 23% using topical treatments, and less than 10% taking placebo will be “cured” after about 1 year. Topical treatments should be reserved for cases with minimal (≤ 20% to 40%) nail involvement.

Evidence

• Oral agents: In a meta-analysis of 43 RCTs of 9730 patients taking oral agents¹ (eg, about 60% to 70% nail involvement,² 12 to 16 weeks of treatment3), the rates of clinical cure after 4 months to 2 years of follow-up were as follows:

  • - In 8 RCTs, rates were 48% for terbinafine and 6% for placebo (number needed to treat [NNT] of 3).
  • - In 9 RCTs, the rate was 31% for “azoles” (mostly itraconazole) and 1.4% for placebo (NNT = 4).
  • - In 15 RCTs, rates were 58% for terbinafine and 46% for azoles (NNT = 9).

• Topical ciclopirox: In 3 RCTs of 928 patients (48 weeks of treatment and about 40% nail involvement),^4,5 “cure” (mycologic and clinical cure) rates were 6% to 8% with topical ciclopirox and 0% to 1% with placebo (NNT = 15 to 23).

• Topical efinaconazole: In 2 identical RCTs of 1655 patients (48 weeks of treatment, assessed at 52 weeks, about 40% nail involvement),⁶ the cure rate was about 16% and about 4% with placebo (NNT of about 9).

  • -In an RCT of 135 patients, after 36 weeks’ treatment and 4 weeks’ follow-up (about 40% nail involvement),⁷ the cure rate was about 22% (9% with placebo; NNT = 8).

Context

• British guidelines suggest laboratory confirmation before treatment,⁸ but only half of Canadian guidelines recommend this.⁹ Culture results take several weeks and have about a 35% false-negative rate.¹⁰ Fungal stains alone have low sensitivity.¹⁰

• Canadian guidelines suggest topical efinaconazole (< 20% nail involvement), efinaconazole with or without oral terbinafine (20% to 60% involvement or for > 3 nails), and oral terbinafine (> 60% involvement).⁹

• The risk of terbinafine-induced liver injury is about 1 in 50 000 to 120 000 prescriptions.¹¹

• Terbinafine treatment without confirmatory testing is likely the most cost-effective approach.¹²

• Although not always statistically different, some RCTs found clinical improvement with 4- to 6-month compared with 3-month oral treatment regimens.^3,13

Implementation

Owing to the slow growth of toenails and lengthy time for “normal” nails to regrow, it can be difficult to determine the optimal length of therapy. Marking the nail at the proximal edge of infection after 3 to 4 months of oral therapy allows for monitoring of success. Ask the patient to return if the infection moves proximal to the mark or does not grow out after 12 to 18 months.¹⁴ Those with persistent infection might benefit from prolonged treatment.

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.