A systematic review 1 on terbinafine in fungal infections of the nails, including nine RCTs (2 227 patients), was abstracted in DARE. Compared with placebo, terbinafine significantly improved the cure rates at 12 weeks; the RR was 9.07 (95% CI: 5.14, 16.02; 3 RCTs, 588 patients). Compared with itraconazole, terbinafine significantly improved the cure rates at the end of treatment (12 to 16 weeks); the RR was 1.64 (95% CI: 1.48, 1.81; 4 RCTs, 1 264 patients). Terbinafine was reported as being better tolerated by patients and physicians than itraconazole (RR 1.22, 95% CI: 1.14, 1.31). Compared with griseofulvin, terbinafine significantly improved the cure rates at 24 weeks; the RR was 1.31 (95% CI: 1.10, 1.56;2 RCTs, 375 patients).
Comment: The limited investigation of heterogeneity and insufficient information on the included studies restrict the assessment of the evidence.
Another systematic review 2 on oral treatments for toenail onychomycosis, including 32 studies, was abstracted in DARE. The included studies compared the following agents with each other and/or placebo: itraconazole (100 to 400 mg/day), terbinafine (250 to 500 mg/day), griseofulvin (500 to 1 000 mg/day), ketoconazole (200 mg/day) and fluconazole (150 to 450 mg/day). The studies used intermittent or continuous regimens of itraconazole. The duration of treatment ranged from 12 weeks to 18 months.
The 3 RCTs (337 patients) of terbinafine versus placebo found that terbinafine increased the mycological cure rates at 12 weeks. One RCT with clinical cure as an outcome found that 250 mg terbinafine for 16 weeks increased the proportion of patients with clear toenails and at least 5 mm unaffected growth, compared with 250 mg terbinafine for 12 weeks or intermittent 400 mg itraconazole. The 2 RCTs (501 patients) of itraconazole versus terbinafine found that terbinafine significantly increased the mycological cure rate at 11 and 12 months' follow-up after 3 months of treatment. The RD was -0.23 (95% CI: -0.15, -0.32) and the NNT was 5 (95% CI: 4, 8). Three RCTs found that terbinafine (250 mg/day) increased the mycological cure rates in comparison with griseofulvin (500 to 1 000 mg/day).
The cure rates in one RCT were 84% with terbinafine versus 45% with griseofulvin. The results from 2 RCTs (481 patients) with different regimens of itraconazole and terbinafine suggested that higher and prolonged dosages did not increase the cure rates. One small RCT (47 patients) found no significant difference between continuous and intermittent terbinafine; the cure rates were 79 and 74%, respectively.
Studies found no significant difference in adverse events between active treatment with itraconazole, terbinafine or fluconazole and placebo.
Comment: The average quality score of the studies was 6.7 out of 12 points. There were several methodological problems, the reported data were incomplete, and the presentation of the results was poor. Most of the trials were funded by pharmaceutical companies.
Primary/Secondary Keywords