Effects of additional oral fosravuconazole l‐lysine ethanolate therapy following inadequate response to initial treatment for onychomycosis: A multicenter, randomized controlled trial

Abstract

AbstractOnychomycosis, a superficial fungal infection, develops when dermatophytes infect nail plate and beds. Fosravuconazole l‐lysine ethanolate (F‐RVCZ), a fourth‐generation azole antifungal agent with potent antifungal activity and few drug interactions, was highly effective in a clinical trial, with a complete cure rate of 59.4% at 48 weeks after treatment initiation. However, some patients were not completely cured. To achieve a higher complete cure rate, additional therapy needs to be examined. We aimed to examine (i) the criteria for additional F‐RVCZ therapy in patients with an inadequate response to initial F‐RVCZ treatment for onychomycosis; (ii) the timing of additional therapy; and (iii) the effects of additional treatment. This was a multicenter, open‐label, three‐arm randomized clinical trial. Patients with onychomycosis were orally administered an approved dose of F‐RVCZ for 12 weeks, and its efficacy was assessed at week 24. Patients who demonstrated ≥55% reduction in nail involvement ratio at week 24 were included in Group X and followed up. Patients with <55% reduction were randomly assigned to follow‐up (Group A) or additional treatment (Group B) groups. The complete cure rate at week 72 in Group X was 73.3%. In Groups A and B, the complete cure rates were 29.6% and 46.7%, respectively, and were significantly different (P = 0.0414, odds ratio 2.08). During the study, 63 adverse drug reactions were recorded in 59 of the 318 patients (18.6%), for which a causal relationship with F‐RVCZ could not be ruled out. In Group B, three of 75 patients (4.0%) experienced three adverse drug reactions, all observed during additional treatment; none were serious. A high complete cure rate is possible without additional F‐RVCZ treatment when nail involvement decreases by ≥55% at week 24; however, when the reduction is <55% at week 24, additional F‐RVCZ treatment should be considered to improve the cure rate.