This retrospective survey represents the first large-scale analysis of actual clinical practice outcomes. In contrast to previous studies, we were able to analyze the efficacy of F-RVCZ therapy for treating onychomycosis of varying severity and clinical type in patients over a wide range of age. In addition, we had minimal exclusions in our survey and thus obtained data that are clinically useful.
Generally, onychomycosis may present as a mixture of clinical types, but the most common type is DLSO [7, 16], and our study found that oral F-RVCZ therapy is effective for treating DLSO. In addition, F-RVCZ therapy exhibited efficacy against dermatophytoma, an intractable clinical feature. Dermatophytoma is a clinical type of onychomycosis typically refractory to systemic therapies and thus can necessitate surgical removal of the diseased nail plate [17]. Although patients with dermatophytomas are often excluded from clinical surveys, we were able to analyze 21 cases. In a previous study in Japan, the complete cure rate for treatment of dermatophytomas with topical agents was 54.5%, and the duration of treatment was > 1 year [10]. In our study, 12 patients (57%) achieved complete cure without any special surgical removal over an average of observation period of 34.3 ± 11.1 weeks. More notably, oral F-RVCZ therapy was also effective against TDO (Fig. 1), the most severe form of onychomycosis [5, 7]. In our study, 3 patients (30%) achieved complete cure within an average observation period of 53.3 ± 11.5 weeks, and our results indicated that the time until therapeutic effect against TDO became clear was longer than for the other types of onychomycosis. Therefore, it was considered that continuous, long-term follow-up was necessary. Moreover, similar to previous reports, the complete cure rate several months after the end of oral administration was higher than the complete cure rate at the end of 12 weeks [13]. In 1 patient, clinical findings improved steadily after the start of treatment but worsened 6 months after the end of oral administration. For these reasons, in actual clinical practice, even if patients finish the 12-week oral administration regimen, we encourage regular visits once every 1–3 months to evaluate the patient's nail condition.
In terms of age, the present study examined a wider range of patients compared with previously reported surveys [15]. Due to aging of the Japanese population, the proportion of patients aged > 80 years is increasing, which could pose problems in the future [17–19]. Therefore, we conducted a more-detailed age-specific evaluation than previous studies. We found no significant difference in improvement rate or time to complete cure between age groups, suggesting that F-RVCZ is effective for all age ranges.
We focused on the complete cure rate because complete cure is often the treatment goal in daily practice. In previous reports, the clinical and complete cure rates at 72 weeks with terbinafine 250 mg/day administered for 12 weeks were 53.6% and 45.8%, respectively, and 60.2% and 55.1%, respectively, for 16 weeks of administration. For itraconazole pulse therapy (400 mg/day), the clinical and complete cure rates at 72 weeks with 3 courses were 31.8% and 23.4%, respectively, and 32.1% and 25.9% (28/108), respectively, for 4 courses [20]. The reported complete cure rate with topical agents is approximately 30–40%, and a long period of administration is required for achieving complete cure [8–10]. In terms of the complete cure rate, our study achieved excellent results. In terms of efficacy, 76.1% (83/109) of patients were evaluated as having significant clearance or greater. Although further investigations are necessary, these results suggest that oral treatment with F-RVCZ is an important option for the treatment of onychomycosis. Many patients can aim for complete cure with oral F-RVCZ therapy. In addition, the duration of oral administration is short, there are fewer drug interactions, and side effects are typically not severe.
F-RVCZ therapy is reportedly effective for the treatment of various dermatomycoses, and it is also reported to be effective option for treating terbinafine-resistant dermatophytes, which have recently attracted clinical attention [21–24]. Our study included 4 cases of onychomycosis with tinea corporis. In all 4 cases, the clinical symptoms of tinea corporis were completely cured by at least 4 weeks. Considering the results of previously reported cases and the simple oral administration regimen in conjunction with few adverse events, F-RVCZ therapy appears to be an effective option for treating other dermatomycoses, although further research is needed.
This study has some limitations. As this was a retrospective study, we did not have a negative control group. The analyses of PSO type were also limited; as the number of cases of PSO was small, more cases need to be analyzed.
Because F-RVCZ has only been available for approximately 2 years and was launched only in Japan, we believe that sharing the actual outcomes of treatment is useful for the treatment of onychomycosis and could aid clinicians worldwide. We hope that our findings prove useful in the actual treatment of onychomycosis.