Long-term Effectiveness of Treatment with Terbinafine vs Itraconazole in Onychomycosis

Journal of American Medical Associations: JAMA Network

ONYCHOMYCOSIS is a common fungal disease. This disease is more common in older age groups and in selected populations, such as swimmers, farmers and individuals with diabetes mellitus or psoriasis.

Antifungal agents, such as terbinafine and itraconazole, are significantly more effective with shorter treatment times. It has previously been demonstrated in a randomized controlled, multicenter, double-blind study that patients treated with continuous terbinafine achieved significantly superior mycological and clinical cure rates compared with patients treated with intermittent itraconazole.

TAKE HOME MESSAGE:

The objective of the present study was to examine long-term mycological and clinical cure rates after treatment with terbinafine and itraconazole for onychomycosis. Similarly, mycological and clinical relapse rates were examined.

Long-term cure rates after first intervention

At the end of follow-up, 46% patients originally treated with terbinafine had negative mycological examination results without the need for a second intervention. Significantly fewer patients treated with itraconazole maintained mycological cure (13%).

When clinical cure rates were considered, 42% terbinafine-treated patients remained clinically cured at the end of follow-up compared with 18% itraconazole-treated patients.

Regarding complete cure, significantly more patients treated with terbinafine maintained complete cure at the end of follow-up without the need for a second intervention.

Relapse rates

At 18 months, 9% of terbinafine-treated patients and 22% itraconazole-treated patients had relapsed mycologically. The relapses in the itraconazole-treated patients continued to increase between months 18 and 36, while relapses in terbinafine-treated patients increased only slightly.

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Response to second intervention with terbinafine

At the end of follow-up, 92% patients who originally received terbinafine as first intervention and 85% patients who originally received itraconazole achieved mycological cure.

CONCLUSION:

Terbinafine is primarily fungicidal in its mode of action as opposed to itraconazole, which is primarily fungistatic. It is tempting to speculate that the fungicidal activity of terbinafine enables it to kill the fungus more rapidly at low concentrations and that this may account for the lower relapse rate observed in this study.

In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.

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Abstract

Objective To examine long-term cure and relapse rates after treatment with continuous terbinafine and intermittent itraconazole in onychomycosis.

Design Long-term prospective follow-up study.

Setting Three centers in Iceland.

Subjects The study population comprised 151 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte toenail onychomycosis.

Interventions In a double-blind, double-dummy study, patients were randomized to receive either terbinafine (250 mg/d) for 12 or 16 weeks or itraconazole (400 mg/d) for 1 week in every 4 for 12 or 16 weeks (first intervention). Patients who did not achieve clinical cure at month 18 or experienced relapse or reinfection were offered an additional course of terbinafine (second intervention).

Main Outcome Measures The primary efficacy criterion was mycological cure, defined as negative results on microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates.

Results Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects. Mycological and clinical relapse rates were significantly higher in itraconazole vs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure.

Conclusion In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.

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