What are the comparative complete‑cure rates for terbinafine versus itraconazole in toenail onychomycosis trials?

1. What the direct comparisons report: the headline numbers

Large head‑to‑head randomized trials found substantially higher cure rates with continuous terbinafine versus intermittent or pulse itraconazole: the LION multicenter trial reported a mycological cure of 76% for terbinafine 250 mg/day versus 38% for itraconazole 400 mg/day at 72 weeks (P < 0.0001) ^[1][5], and other controlled trials reported mycologic cure rates around 81% for terbinafine versus 63% for itraconazole (P < 0.01) ^[6]. Meta‑analytic pooling of trials comparing continuous terbinafine (12 weeks) to intermittent itraconazole found significantly higher odds of mycological cure with terbinafine (OR ≈ 2.3) ^[5]. These results map onto reports that complete cure rates after terbinafine were “approximately twice as high” as for itraconazole in several analyses ^[7].

2. Long‑term durability and relapse: what follow‑up studies show

Longitudinal follow‑up amplifies the terbinafine advantage: a 5‑year blinded prospective study found superior long‑term mycological and clinical efficacy and lower relapse with continuous terbinafine versus intermittent itraconazole, with relapse rates higher in itraconazole‑treated patients (mycological relapse 53% vs 23%, clinical relapse 48% vs 21%) ^[8]. The same long‑term dataset reported mycological cure of 46% for terbinafine versus 13% for itraconazole at extended follow‑up in that cohort ^[5][8], underscoring that initial differences persist or widen over time.

3. The caveats: definitions, regimens and heterogeneity in reported “complete cure”

“Complete cure” often combines clinical appearance (normal nail) with laboratory mycological negativity, but trials vary in endpoints, timing, and whether they report mycological cure or composite complete cure; this heterogeneity produces wide reported ranges for terbinafine complete‑cure rates (reported in some studies from ~14% up to 90% when single‑nail analyses or different endpoints are used) and clinical cure ranges of roughly 54–76% in continuous terbinafine trials ^[3][4]. Differences in itraconazole dosing (continuous 200 mg/day vs pulse 400 mg/day for one week each month), trial length, patient selection and organism type (dermatophyte vs non‑dermatophyte) further complicate direct comparisons ^[9][10].

4. Mechanistic and safety context that influences outcomes

Pharmacology offers a plausible explanation for the efficacy gap: terbinafine is fungicidal against dermatophytes with nail concentrations far above its minimum fungicidal concentration, while itraconazole is primarily fungistatic at typical nail concentrations, which may blunt long‑term eradication ^[9]. Safety and tolerability data are mixed in reporting: some reviews note adverse events and discontinuations for both drugs with itraconazole sometimes characterized as “safer” in specific analyses, while head‑to‑head trials show similar tolerability overall but higher discontinuation for some agents in pooled analyses ^[11][1].

5. Bottom line and practical interpretation

Across randomized trials, long‑term follow‑up studies, and meta‑analyses in toenail dermatophyte onychomycosis, continuous oral terbinafine (commonly 250 mg/day for 12–16 weeks) produces higher mycological and complete‑cure rates than typical itraconazole regimens, with some large trials reporting roughly twofold higher cure percentages (for example, 76% vs 38% mycological cure in the LION study and 81% vs 63% in another multicenter trial) and sustained advantages in relapse rates over years ^[1][6][8]. Limitations in cross‑study comparisons arise from variable endpoint definitions, dosing schedules, and follow‑up durations, and clinicians weigh efficacy alongside individual patient factors and safety profiles when selecting therapy ^[3][4][11].