Is Testing Needed Before Treating Onychomycosis With Terbinafine?

Graeme M. Lipper, MD


April 19, 2016

Cost-Effectiveness of Confirmatory Testing Before Treatment of Onychomycosis

Mikailov A, Cohen J, Joyce C, Mostaghimi A
JAMA Dermatol. 2016;152:276-281

Onychomycosis is the most common cause of chronic nail thickening and discoloration, affecting up to 14% of adults in North America.[1,2] Antifungal treatments range in efficacy, with systemic drugs such as oral terbinafine and itraconazole yielding superior mycologic and complete cure rates when compared with topicals such as ciclopirox, efinaconazole, and tavaborole. Nevertheless, many patients and clinicians favor the less effective and more expensive topical agents due to fear of side effects such as hepatotoxicity with the cheaper systemic agents.

When evaluating a patient with yellow, discolored nails, clinicians can choose to treat empirically with oral or systemic antifungal drugs or perform in-clinic (potassium hydroxide [KOH] prep, dermatophyte test medium fungal culture) or laboratory (nail clipping for periodic acid-Schiff [PAS] staining) testing to confirm the diagnosis of onychomycosis before prescribing antifungal therapy. The American Academy of Dermatology recommends confirmatory testing first as a means to reduce wasteful spending and treatment-associated side effects, but this recommendation was based on data from a 1999 study.[2]

As Mikailov and colleagues note, two main changes have happened since then:

  1. The price of oral terbinafine has plummeted from over $500 to as low as $10 for a 3-month course; and

  2. New, highly effective but pricey topical antifungals (efinaconazole, tavaborole) are now approved by the US Food and Drug Administration for the treatment of onychomycosis, with more topicals under development.

In this context, does it still make sense to order confirmatory testing prior to treating onychomycosis with oral terbinafine? What about before prescribing the more expensive efinaconazole 10%?

To address these questions, Mikailov and colleagues performed a literature review to compare the relative costs of:

  1. Empirical antifungal therapy with oral terbinafine (12-week continuous course, 250 mg/day) or topical efinaconazole 10% (1 drop/nail/day x 48 weeks);

  2. Pretreatment confirmatory testing with KOH staining followed by PAS evaluation of the nail plate if the KOH was negative; and

  3. Pretreatment confirmatory testing with PAS evaluation.

Because oral terbinafine may cause rare liver injury, investigators also calculated the cost to avoid harm when treating patients with empirical terbinafine. Based on prior data,[3] they estimated that 75% of all patients presenting with nail dystrophy had onychomycosis. Using this disease prevalence, empirical treatment with terbinafine saved $47 per patient vs the KOH screening model and $135 per patient vs pretreatment PAS evaluation. In contrast, screening with KOH scraping or confirmatory PAS testing as a prerequisite for treatment with efinaconazole 10% saved $272 or $406 per treated nail, respectively. Perhaps most strikingly, it would take up to $90.2 million of PAS testing to prevent a single case of clinically relevant hepatotoxicity from oral terbinafine.


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