A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement

BACKGROUND: Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. OBJECTIVES: Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. METHODS: In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. RESULTS: In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59.2% vs. 45.0%; P = 0.03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries. CONCLUSIONS: Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.     

A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis

BACKGROUND: Treatment failures and relapses are not uncommon in onychomycosis. Therefore, it is worthwhile to consider the combination of systemic and topical antifungals to improve the cure rates further and to reduce the duration of systemic treatment. OBJECTIVES: To evaluate and compare itraconazole pulse therapy combined with amorolfine with itraconazole alone in the treatment of Candida fingernail onychomycosis. METHODS: Ninety patients with moderate to severe Candida fingernail onychomycosis were randomized into two treatment groups of 45 subjects each. Group 1 received itraconazole pulse therapy for 2 months and applied amorolfine 5% solution nail lacquer for 6 months, while group 2 received monotherapy with three pulses of itraconazole. The primary efficacy criterion was the result of mycological examination at 3 months. The secondary criterion was the combined mycological and clinical response at 9 months. A pharmacoeconomic analysis was also performed to compare the cost-effectiveness of combined therapy vs. monotherapy. RESULTS: Eighty-five patients were analysed (73 women and 12 men, mean +/- SD age 44.2 +/- 12.9 years). Patients had a mean +/- SD of 3.64 +/- 2.0 nails involved and 228.6 +/- 148.0 mm2 of their nail surface diseased. The mean duration of onychomycosis was 11 months. Paronychial involvement was evident in 71 patients. C. albicans was isolated in 85 cases, C. parapsilosis in three and other Candida species in two cases. Side-effects were uncommon and in only one case led to withdrawal. At the 3-month visit, mycological cure was seen in 32 (74%) of 43 patients in group 1 and in 25 (60%) of 42 patients in group 2. At the 9-month visit, a global cure was seen in 40 patients (93%) in group 1 and in 34 patients (81%) in group 2. Statistical analysis showed no statistically significant difference (P > 0.1) between the two treatment groups. The cost per cure ratio was 1.63 and 1.70euro for groups 1 and 2, respectively. CONCLUSIONS: The combination of amorolfine and oral itraconazole, which interfere with different steps of ergosterol synthesis, exhibited substantial synergy. Compared with oral itraconazole alone, the combination achieved greater mycological cure and increased total cure rate. However, no statistically significant difference was documented for this number of observations. Combination treatment with amorolfine and two pulses of itraconazole is at least as safe and effective as three pulses of itraconazole, with a lower cost per patient. In our opinion, the addition of amorolfine to oral itraconazole pulse therapy is of value in the treatment of moderate to severe Candida fingernail onychomycosis.     

Efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years

Background Standard treatment for onychomycosis often results in less than half of subjects achieving disease‐free nails. Onychomycosis is even more challenging to treat as relapses and re‐infections are common. Objective To determine if a prophylactic effect exists when a treatment with amorolfine nail lacquer (ANL), with half the frequency of the standard regimen, is instituted following successful treatment of dermatophytic toenail onychomycosis with matrix involvement. Methods Efficacy and safety of a group treated with ANL (once every 2 weeks) were compared with that of an untreated group in a 36‐month (3 years), single‐centre, randomized, open‐label, comparison study. Subjects to be included in the study were required to be cured of confirmed onychomycosis with matrix involvement after an initial treatment with either ANL + oral terbinafine or oral terbinafine alone in a previous study. Prophylaxis of onychomycosis was assessed by global recurrence rate, confirmed onychomycosis, clinical recurrence and mycological recurrence. Results A total of 52 subjects were enrolled (26 in each group) in the study. Throughout the study, recurrences occurred more quickly in the untreated group compared with that in the ANL group. Statistically significant differences were observed at month 12 (ANL, 8.3%; untreated, 31.8%; P = 0.047). At endpoint, 70.8% of the subjects treated with ANL remained cured compared to 50% in the untreated group (P = 0.153). Recurrence was delayed by nearly 200 days for the ANL group compared with that of the untreated group. Amorolfine was safe and well tolerated during the study, with no treatment‐related adverse events. Conclusion These results suggest that amorolfine nail lacquer may be effective and is safe for use as a prophylactic treatment for the recurrence of onychomycosis.     

Efficacy and tolerability of amorolfine 5% nail lacquer in combination with systemic antifungal agents for onychomycosis: A meta‐analysis and systematic review

The efficacy and safety of amorolfine 5% nail lacquer in combination with systemic antifungal agents in the treatment of the onychomycosis were evaluated. According to our meta‐analysis, combination treatment of amorolfine 5% nail lacquer and systemic antifungals can result in higher percentage of complete clearance of onychomycosis. It showed that the experimental combination group was more effective than monotherapy of the systemic antifungals [OR (odds ratio) = 1.97, 95%CI (95% confidence interval) = 1.44–2.69], and no more adverse events happened with the addition of amorolfine 5% nail lacquer (OR = .96, 95%CI = .56–1.63, p = .95). This effect strengthens the fact that amorolfine 5% nail lacquer in combination with systemic antifungal agents was better than the monotherapy of systemic antifungals like itraconazole and terbinafine.     

The use of an intermittent terbinafine regimen for the treatment of dermatophyte toenail onychomycosis

Objective  To compare the efficacy and safety of intermittent terbinafine with standard courses of terbinafine and itraconazole for dermatophyte toenail onychomycosis.
Design  Data from a Canadian study of continuous terbinafine (CTERB) and intermittent itraconazole (III) was compared to an intermittent terbinafine regimen (TOT) using similar protocol to the randomized study.
Interventions  Terbinafine 250 mg/day for 4 weeks followed by 4 weeks of no terbinafine and then an additional 4 weeks of terbinafine 250 mg/day (TOT); terbinafine 250 mg/day for 12 weeks (CTERB); itraconazole pulse of 200 mg twice daily for 7 days on, 21 days off, three pulses given (III).
Results  At 72 weeks, mycological cure rates (negative KOH and culture) were 36 of 43 (83.7%), 25 of 32 (78.1%), and 17 of 30 (56.7%), for the TOT, CTERB, and III groups, respectively ( P =  0.01 for TOT vs. III). Effective cure rates (simultaneous mycological cure and ≤10% nail plate involvement) were 34 of 43 (79.1%), 21 of 32 (65.6%), and 11 of 30 (36.7%), respectively ( P <  0.001 for TOT vs. III; P =  0.02 for CTERB vs. III). No significant differences in effective and mycological cure rates were noted between the two terbinafine groups. Adverse events reported were similar to those reported in the respective package inserts. Most adverse events were mild to moderate, transient, and did not require interruption of the drug regimens. No serious adverse events were reported.
Conclusions  A TOT intermittent terbinafine regimen provided similar efficacy and safety to the gold standard continuous terbinafine regimen and better effective cure rates than pulse itraconazole therapy.

Conflicts of interest

None declared     

Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus

BACKGROUND: Oral terbinafine and oral itraconazole are two of the most common agents used for the treatment of toenail dermatophyte onychomycosis. Despite the fact that diabetic patients are more likely to have onychomycosis than normal individuals are, there is little research into the efficacy of standard oral regimens of terbinafine and itraconazole for onychomycosis in the diabetic population. STUDY DESIGN: We present a prospective, randomized, single-blind, parallel group, comparator-controlled, multi-centre study designed to assess the efficacy of the pulse itraconazole (200 mg twice daily, 1 week on, 3 weeks off, for 12 weeks) vs. continuous terbinafine (250 mg once daily for 12 weeks) oral therapies in the treatment of dermatophyte toenail distal and lateral subungual onychomycosis (DLSO) in the diabetic population. EFFICACY PARAMETERS: Primary efficacy measures included mycological cure rate (negative KOH and culture) and effective cure (mycological cure plus nail plate involvement of 10% or less) at Week 48. RESULTS: At Week 48, mycological cure was attained by 88.2% (30 of 34) and 79.3% (23 of 29) of patients in the itraconazole and terbinafine groups, respectively (P not significant). Effective cure (mycological cure with 相似文献   

Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain

Objective In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy.
Patients/Methods A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl®, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group I-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed.
Results At week 12, mycological cure was attained in 42 of 45 patients (93·3%) in group AI-6, 29 of 35 patients (82·9%) in group AI-12, and 14 of 34 patients in group I-12. The difference between both combination groups and the control group were significant ( P  < 0·001). The global cure rate at week 24 was 83·7% (36 patients) in group AI-6, 93·9% (31 patients) in group AI-12, and 68·8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant ( P  < 0·05).
Conclusions These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.     

特比萘芬治疗老年人甲真菌病多中心临床疗效和安全性评价

目的：观察特比萘芬连续疗法治疗60岁以上甲真菌病患者的疗效、安全性和耐受性。方法：120例老年甲真菌病患者口服特比萘芬250mg,每日1次,指甲真菌病患者连续口服12周,趾甲真菌病患者连续口服16周;指甲真菌病患者在服药后第36周、趾甲真菌病患者在服药后第52周评价最终疗效和不良反应;同时检查血、尿常规,肝、肾功能。结果：在停药时及第36周时,指甲真菌病患者的临床有效率分别为68．8％和96．9％,真菌学治愈率分别为87．5％和96．9％;在停药时及第52周时,趾甲真菌病患者的临床有效率分别为44．2％和87．2％。真菌学治愈率分别为62．8％和96．5％。不良反应发生率为8．3％,主要为胃肠道反应。未发现特比萘芬与其他药物间的相互作用。结论：特比萘芬治疗老年人甲真菌病有效,且安全、耐受性良好。     

Combination of pulse therapy with terbinafine tablets and topical terbinafine cream for the treatment of dermatophyte onychomycosis: a pilot study

We performed a pilot study to assess the safety and efficacy of pulse therapy with terbinafine tablets in 66 patients with dermatophyte onychomycosis. One pulse consisted of oral terbinafine tablets (500 mg/day) given for 1 week followed by a 3-week interval. Topical 1% terbinafine cream was applied daily. The number of pulses was determined by the extent of improvement in the affected nails and by the patient's requests, up to a maximum of six pulses. Efficacy was assessed based on both clinical and mycological examinations 1 year after treatment initiation. We observed a complete cure in 51 patients (77.3%), marked improvement in five patients (7.6%), improvement in five patients (7.6%) and slight improvement in one patient (1.5%). Four patients (6.0%) showed no change. In the patients who were completely cured, the average number of pulses used was 3.7 +/- 1.4 pulses and the treatment duration was 3.3 +/- 1.6 months. Nine patients experienced adverse effects, consisting of gastrointestinal disturbance (eight patients) and drug-induced eruption (one patient). There were no abnormal findings in the laboratory tests, including liver function tests. In summary, terbinafine pulse therapy in combination with topical application of terbinafine cream appeared safe and effective in this pilot study.     

A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis

In a randomized, double-blind, double-placebo, multicentre study, terbinafine 250 mg daily for 12 weeks was compared with fluconazole 150 mg once weekly for 12 or 24 weeks in the treatment of onychomycosis. A total of 137 patients with culture-confirmed onychomycosis was divided into three groups: group A received terbinafine for 12 weeks, group B received fluconazole for 12 weeks, while group C received fluconazole for 24 weeks. At completion of the study (week 60), the mycological cure rate was higher in the terbinafine group than in the fluconazole groups: 89% vs. 51% and 49%, respectively (P < 0.001). The length of unaffected nail increased until week 24 in group B and until week 36 in group C, but was still increasing in group A at the final visit (week 60). Complete clinical cure of the target nail at week 60 was 67% in the terbinafine group, compared with 21% and 32% in the fluconazole groups, respectively. The incidence of adverse events was low for both study agents. We conclude that terbinafine 250 mg daily for 12 weeks is significantly more effective in the treatment of onychomycosis than fluconazole 150 mg once weekly for either 12 or 24 weeks.     

The efficacy of fractional carbon dioxide (CO2) laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis

Background: Although systemic and topical antifungal agents are widely used to treat onychomycosis, oral medications can cause adverse effects and the efficacy of topical agents is not satisfying. Currently, laser treatment has been studied for its efficacy in the treatment of onychomycosis. Our study was aimed to evaluate the efficacy of fractional carbon dioxide (CO₂) laser treatment combined with terbinafine cream for 6 months in the treatment of onychomycosis and to analyze the influencing factors. Methods: A total of 30 participants (124 nails) with clinical and mycological diagnosis of onychomycosis received fractional CO₂ laser treatment at 2-week interval combined with terbinafine cream once daily for 6 months. The clinical efficacy rate (CER) was assessed from the percentage of fully normal-appearing nails or nails with ≤5% abnormal appearance, and the mycological clearance rate (MCR) was assessed from the percentage of nails with negative fungal microscopy. Results: The CER was evaluated at 3 time points: at the end of treatment (58.9%), at 1 month after the last treatment (63.5%), and at 3 months after the last treatment (68.5%). The MCRs at 1 month and 3 months after the last treatment were 77.4 and 74.2%, respectively. The evaluation of influencing factors showed significantly higher CER (p < 0.05) in nails of participants with age <50 years, distal lateral subungual onychomycosis (DLSO), superficial white onychomycosis (SWO), nail thickness <2 mm, affected first-to-fourth finger/toenails, Trichophyton rubrum, and Trichophyton mentagrophytes. All participants experienced tolerable mild burning sensation during laser treatment, but there were no other adverse reactions reported. Conclusions: Fractional CO₂ laser treatment combined with terbinafine cream for 6 months was an effective and safe method for the treatment of onychomycosis. There were 5 factors that positively influenced the treatment outcome: age, clinical type of onychomycosis, nail thickness, involved nail, and species of fungus.     

A comparative evaluation of combination therapy of fluconazole 1% and urea 40% compared with fluconazole 1% alone in a nail lacquer for treatment of onychomycosis: therapeutic trial

Abstract This is a randomized, double-blind study enrolling 70 patients with onychomycosis of the finger and toenails. Clinical and mycological efficacies as well as measures of safety were assessed monthly for a maximum of 6 months of treatment. The treatment regimens were: fluconazole 1% and fluconazole 1% with urea 40%. These results indicated topical treatment of onychomycosis with a combination of fluconazole 1% and urea 40% was more effective (82.8%) than fluconazole 1% (62.8%) nail lacquer alone in treatment of dermatophytic onychomycosis. Fluconazole was well tolerated and side effects were negligible. At the end of therapy and the end of the 6-month follow-up, fluconazole 1% and urea 40% demonstrated statistically significant superiority in clinical and mycological responses compared with fluconazole 1% alone.     

不同方案国产特比萘芬治疗头癣随机双盲比较研究

目的：评价国产特比萘芬治疗头癣的疗效及安全性,探索最佳给药方案。方法：头癣患者随机分成三组,Ａ组连服２周,Ｂ组连服４周,Ｃ组连服１周后间隔２周再连服１周,４周治疗中不口服特比萘芬时给安慰剂,按体重给药,于第８周末评价疗效及安全性。结果：７６例可评价患者分离的病原菌主要包括犬小孢子菌４８株（６２．３％）、须癣毛癣菌２４株（３１．２％）。于８周末评价时,治愈率分别为６４％、８８．９％和８３．３％。只见轻微副作用。结论：口服国产特比萘芬治疗头癣疗效高、安全性好、患者耐受性好,连服药１周间隔２周再连续服药１周,为我们的推荐方案。     

Terbinafine (Lamisil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial

BACKGROUND: Diabetes mellitus (DM) affects an estimated 175 million people world-wide. Approximately one-third of patients with DM have toenail onychomycosis. OBJECTIVES: To determine the efficacy and safety of terbinafine treatment of toenail onychomycosis in patients with DM receiving insulin and/or oral antidiabetic agents. Special interest was focused on potential drug interactions with oral hypoglycaemic substances. METHODS: In a multicentre trial, patients suffering from insulin-dependent DM (IDDM) or non- insulin-dependent DM (NIDDM) with toenail onychomycosis were treated for 12 weeks with oral terbinafine 250 mg daily and followed up to 48 weeks. In addition to clinical, mycological and laboratory investigations, blood glucose levels were monitored. RESULTS: At the end of the trial (week 48), a mycological cure rate of 73% was achieved. The rates of clinical cure and complete cure (mycological cure plus clinical cure) were 57% and 48%, respectively. There was no statistically significant difference between the NIDDM and IDDM groups with respect to the cure rates (P > 0.05). No hypoglycaemic episode was reported and none of the patients had hypoglycaemia during the treatment phase. CONCLUSIONS: With excellent cure rates and a good tolerability profile, terbinafine should continue to be a drug of choice for the treatment of toenail onychomycosis in the rising number of NIDDM patients receiving multiple medication.     

Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter,double‐blind,randomized phase III study

Onychomycosis is a highly prevalent and intractable disease. The first‐line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double‐blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20–50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end‐point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.     

Evaluation of the efficacy and tolerability of oral terbinafine (Daskil) in patients with seborrhoeic dermatitis. A multicentre, randomized, investigator-blinded, placebo-controlled trial

BACKGROUND: Previous uncontrolled trials have suggested that oral terbinafine, an antimycotic allylamine compound, could be useful in the treatment of seborrhoeic dermatitis. OBJECTIVES: To investigate in a placebo-controlled trial the clinical efficacy of oral terbinafine (Daskil(R), Mipharm, Milan, Italy) in patients with moderate to severe seborrhoeic dermatitis. METHODS: Sixty outpatients (mean +/- SD age 37 +/- 11 years; 32 men and 28 women) with moderate to severe seborrhoeic dermatitis were enrolled in a multicentre, randomized, placebo-controlled, investigator-blinded, parallel-group, 12-week study. After a 2-week wash-out period, enrolled patients were randomized to treatment with oral terbinafine 250 mg daily (n = 30) or placebo (moisturizing ointment) (n = 30) applied twice daily for 4 weeks (weeks 0-4). Patients were followed up for an additional 8 weeks after completion of treatment and were clinically evaluated at weeks 0, 2, 4 and 12 by an investigator unaware of the patient's type of treatment. The primary end-point of the study was clinical evaluation of erythema, scaling and itching, each scored on a 0-3 scale. A global clinical score, representing the sum of each evaluated symptom, was also calculated. RESULTS: Demographic and clinical data were equally balanced between the placebo and terbinafine groups. All enrolled patients concluded the study. At baseline, the mean +/- SD global clinical score was 7.4 +/- 1.3 in the placebo group and 7.7 +/- 1.0 in the terbinafine-treated group. At weeks 4 and 12 the mean +/- SD global clinical score in the placebo group was 5.9 +/- 1.7 and 6.3 +/- 1.2, respectively, which was not significantly different from baseline. As compared with baseline values and the placebo group, terbinafine treatment significantly (P < 0.0001, Tukey-Kramer test) reduced the mean +/- SD global clinical score (to 1.0 +/- 1.1 at week 4, and 1.2 +/- 1.4 at week 12), as well as the individual erythema, scaling and itching scores. No serious adverse events were recorded during the study in either group. CONCLUSIONS: This is the first controlled trial that has shown oral terbinafine to be effective in the treatment of moderate to severe seborrhoeic dermatitis. Clinical improvement following 4 weeks treatment with terbinafine was maintained 8 weeks after completing treatment.     

Single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis

OBJECTIVE: Efficacy and safety of sequential pulse therapy with itraconazole and terbinafine were compared with pulse terbinafine alone in the treatment of toenail onychomycosis. METHODS: This was a 72-week prospective, single-blind, randomized, multicenter, comparative, parallel group, nonindustry-sponsored trial. A total of 190 patients were recruited from 3 outpatient dermatology offices in North America. Patients were at least 18 years old and had a clinical and mycologic diagnosis of dermatophyte toenail onychomycosis. Patients were randomly assigned to receive sequential pulse therapy (IIT) with 2 pulses of itraconazole followed by 1 or 2 pulses of terbinafine (itraconazole pulse is 200 mg twice daily for 1 week and terbinafine pulse is 250 mg twice daily for 1 week) versus 3 or 4 pulses of terbinafine (TTT). Main outcome measures at week 72 evaluated mycologic cure rate (negative light microscopy and culture), clinical cure (nail appears completely or totally normal), complete cure (clinical and mycologic cure), and effective therapy (mycologic cure and clinical response with at least 5 mm of new, uninvolved nail growth). RESULTS: At week 72, in the IIT versus TTT groups, the mycologic cure rate was 54 of 75 (72.0%) versus 44 of 90 (48.9%), clinical cure rate was 42 of 75 (56.0%) versus 35 of 90 (38.9%), effective therapy 49 of 75 (65.3%) versus 41 of 90 (45.6%), and complete cure 39 of 75 (52.0%) versus 29 of 90 (32.2%), respectively. Both regimens were well tolerated with no new adverse effects being identified. The rate of permanent discontinuation of therapy because of adverse effects was 2 of 81 (2.5%) with IIT and 2 of 95 (2.1%) with TTT. Each of the adverse effects normalized over time. The number of patients who reported an adverse effect in the 2 groups was 12 of 81 (14.8%) versus 22 of 95 (23.2%), respectively. All these adverse effects were reversible and mild to moderate in severity. CONCLUSION: Sequential pulse therapy with itraconazole and terbinafine is effective and safe for the treatment of dermatophyte toenail onychomycosis.