Limited effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole and terbinafine) in the current epidemic of altered dermatophytosis in India: results of a randomized pragmatic trial.

Abstract

Dermatophytic infections have undergone unprecedented changes in India in the recent past. Clinical trials to find out the effectiveness of the four main oral antifungal drugs are lacking. We tested the effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic relapsing tinea corporis, tinea cruris and tinea faciei in an investigator-initiated, randomized, pragmatic trial. Two hundred patients with microscopy-confirmed tinea were allocated to four groups (50 patients in each group): fluconazole 5 mg kg-1 per day, griseofulvin 10 mg kg-1 per day, itraconazole 5 mg kg-1 per day and terbinafine 7·5 mg kg-1 per day. Allocation was performed by concealed block randomization and the patients were treated for 8 weeks or until cure. Effectiveness was calculated based on intention-to-treat analysis. The trial was registered with the Clinical Trials Registry India (CTRI/2017/04/008281). At 4 weeks, all drugs were similarly ineffective, with cure rates being 8% or less (P = 0·42). At 8 weeks, the numbers of patients cured were as follows: fluconazole 21 (42%), griseofulvin seven (14%), itraconazole 33 (66%) and terbinafine 14 (28%) (P < 0·001). Itraconazole was superior to fluconazole, griseofulvin and terbinafine (adjusted P ≤ 0·048). Relapse rates after 4 and 8 weeks of cure with the four treatments were not different (P ≥ 0·42). Numbers needed to treat (vs. griseofulvin), calculated on the basis of cure rates at 8 weeks, were as follows: fluconazole 4, itraconazole 2 and terbinafine 8. The results show limited effectiveness of all four antifungal drugs. In view of cure rates and the number needed to treat, itraconazole is the most effective drug, followed by fluconazole (daily), terbinafine and then griseofulvin, in chronic and chronic relapsing dermatophytosis in India. What is already known about this topic? Oral antifungal drugs are considered to have a high cure rate in tinea corporis, tinea cruris and tinea faciei. Unprecedented changes have been noticed in the last few years in India in the morphology, course and treatment responsiveness of tinea; however, data about the effectiveness of oral antifungals are lacking. What does this study add? Our results show limited effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole and terbinafine) in the current epidemic of altered dermatophytosis in India. Among the four drugs tested, oral itraconazole is the most effective. Linked Comment: Elewski. Br J Dermatol 2020; 183:798-799.