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Evans EG, Sigurgeirsson B, for the LION Study Group. Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. BMJ. 1999 Apr 17;318:1031-5.
In patients with toenail onychomy-cosis, does continuous terbinafine heal infection better than intermittent itraconazole?
Randomised (concealed), blinded (patients and outcome assessors), controlled trial with 72-week follow-up.
35 centres in 6 countries (Finland, Germany, Iceland, Italy, the Netherlands, and the United Kingdom).
507 patients who were 18 to 75 years of age and had a clinical, mycologically confirmed diagnosis of toenail onychomycosis with an affected great toenail capable of regrowth. Exclusion criteria included infections other than dermatophyte infection; use of systemic or topical antifungal treatment within the previous 12 months and 4 weeks, respectively; use of drugs that might interact with study drugs; systemic conditions that might alter the pharmacodynamics of study drugs; or radiotherapy, chemotherapy, or immunosuppressive therapy in the previous 12 weeks. 496 patients (mean age 50 y, 58% men) were included in the study. Follow-up was 83% for mycological cure and 84% for clinical cure.
Patients were allocated to 1 of 4 groups: terbinafine, 250 mg/d for either 12 (n = 124) or 16 weeks (n = 120); or itra-conazole, four 100-mg capsules daily for 1 week every 4 weeks, for either 12 (n = 126) or 16 weeks (n = 126). Matching placebo was used to maintain blinding.
Main outcome measures
Mycological and clinical cure rates.
At 72 weeks, patients in both terbinafine groups had greater rates of mycological cure (P < 0.001) and clinical cure (P £ 0.002) than did those in the itra-conazole groups (Table).
In patients with toenail onychomy-cosis, continuous terbinafine healed infection better than intermittent itraconazole.
Source of funding: Novartis Pharmaceuticals Corporation.
For correspondence: Dr. E.G. Evans, Public Health Laboratory Service (PHLS) Mycology Reference Laboratory, University of Leeds and General Infirmary, Leeds LS2 9JT, England, UK. FAX 44-113-233-5587.
Continuous terbinafine (Ter) for 12 (T12) or 16 (T16) weeks vs intermittent itraconazole (Itr) for 3 (I3) or 4 (I4) cycles for toenail onychomycosis*
Outcomes at 72 wk Comparison Ter Itr RBI (95% CI) NNT (CI)
Mycological cure T12 vs I3 76% 38% 98% (54 to 160) 3 (3 to 5)
T12 vs I4 76% 49% 54% (25 to 94) 4 (3 to 8)
T16 vs I3 81% 38% 111% (65 to 176) 3 (2 to 4)
T16 vs I4 81% 49% 65% (34 to 106) 4 (3 to 6)
Clinical cure T12 vs I3 54% 32% 69% (23 to 136) 5 (3 to 12)
T12 vs I4 54% 32% 67% (22 to 132) 5 (3 to 12)
T16 vs I3 60% 32% 89% (39 to 163) 4 (3 to 7)
T16 vs I4 60% 32% 87% (38 to 159) 4 (3 to 7)
*Other abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
Topical antifungal agents for onychomycosis have generally been disappointing. Recent use of oral antifungal agents in selected patients has had encouraging results because of more efficient bioavailability and increased medication adherence.
Evans and colleagues' study results are consistent with those from previous studies. However, the following points must be noted. First, standard measures of liver and kidney function and anaemia must be carefully monitored with the co-administration of most currently approved oral agents. Specifically, multiple results on liver function tests that are elevated, regardless of other haematological parameters, may necessitate that the drugs be withheld (1).
Second, onychomycosis can result from yeast, saprophytic species, or other mycoses, as well as dermatophytes. The agents used in this study have had variable success at eradicating many infective species.
Third, the appearance of fungal nails is highly variable. Therefore, a clinical cure, which was one of the outcomes used in this study, is hard to define.
Fourth, the potential for synergistic drug interactions resulting in adverse effects on the liver or changed plasma levels of other drugs is a substantial problem with the use of most antifungal agents. Anticoagulants, other prescription drugs, and many non-prescription drugs may interact with these agents.
Finally, the literature shows that terbinafine is the least costly and most effective drug for treating onychomycosis (2), and this study provides further evidence for its use.
Allan S. Goldberg, DPM
St. John's Episcopal Hospital
Far Rockaway, New York, USA
1. Hay RJ. J Am Acad Dermatol. 1993;29: S50-4.
2. Angello JT, Voytovich RM, Jan SA. Am J Manag Care. 1997;3:443-50.