Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects.

Dermatophytoma is a little-known, difficult to treat fungal infection that complicates onychomycosis. First described by Roberts and Evans in the late 1990's, dermatophytoma presents as a dense concentration of fungal hyphae within or under the nail plate and is generally white or yellow/brown in color, and linear (streaks) or round (patches) in shape; primary etiologic organisms are dermatophytes. Oral antifungals have limited success in treating dermatophytoma owing to difficulties accessing and penetrating what is hypothesized to be a fungal biofilm. In this respect, dermatophytoma is generally treated with a combination therapy approach, often including both surgical and pharmacologic intervention for improved outcomes. A post-hoc assessment of Phase II tavaborole onychomycosis studies was conducted in order to assess the prevalence of dermatophytoma and outcomes in patients treated with topical tavaborole. Of the 366 subjects enrolled in the Phase II onychomycosis studies, we identified 102 cases of dermatophytoma; 21 of 86 (24.4%) subjects treated with tavaborole were able to achieve complete resolution of dermatophytoma by day 180, while no subjects on vehicle obtained resolution. Similarly, 23 of 86 subjects (26.7%) treated with tavaborole solution had complete resolution of dermatophytoma by day 360, while only 1 of 16 subjects (6.3%) on vehicle obtained resolution. Moreover, 13 of 19 subjects (68.4%) treated with tavaborole solution were able to sustain resolution, while only 6 of 19 (31.6%) had reoccurrence, of dermatophytoma during the 180-day washout period (day 360). We present 5 cases of dermatophytoma identified in Phase II trials that responded in a positive manner following treatment with tavaborole solution for onychomycosis of the great toenail. Although not representative of all subject outcomes, these findings provide insight into the use of topical tavaborole for dermatophytoma, a condition previously thought to respond only to oral or combination therapy.

J Drugs Dermatol. 2018;17(3):347-354.

Tavaborole in Difficult-to-Treat Onychomycosis Cases: A Post-hoc Assessment of Phase III Subjects.

Toenail onychomycosis is a chronic fungal infection that often requires prolonged treatment in order to effectively manage pathogenic organisms and obtain a clear nail. Traditionally, certain clinical features of onychomycosis, including the presence of substantial lateral disease, focal fungal masses, yellow/brown streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment prognosis and have proven difficult-to-treat with oral or traditional topical therapies. Owing to the novel features of topical tavaborole, we sought to understand the potential utility of tavaborole in difficult-to-treat onychomycosis. A blinded, post-hoc assessment of Phase III trials was conducted, focusing on initial presentation, midpoint assessment (24 weeks), and final outcomes (52 weeks) in subjects identified as having difficult-to-treat onychomycosis and treated for 48 weeks with once-daily application of either tavaborole 5% solution or vehicle. Our post-hoc analysis identified 84 difficult-to-treat cases (tavaborole 5%; n=60; vehicle, n=24) in subjects with toenail onychomycosis due to Trichophyton rubrum or Trichophyton mentagrophytes. No subjects identified as difficult-to-treat and treated with vehicle achieved a complete cure, while 6 subjects treated with tavaborole 5% attained a completely clear nail and negative mycology. Similarly, 7 subjects treated with tavaborole 5% solution achieved an almost complete cure (≤10% involvement and negative mycology) while 1 subject on vehicle achieved an almost complete cure. We present a case series of 4 patients, of varying age and difficult-to-treat clinical features, which responded positively to tavaborole 5% solution. Three of the subjects achieved complete cure after being treated with tavaborole 5%, with one additional subject (an 88-year-old female) achieving an almost complete clear nail by treatment end. The outcomes presented here may not be reflective of patients that may present with these clinical characteristics. Additional investigations would be useful in order to assess the value of topical tavaborole 5% solution in difficult-to-treat clinical presentations of onychomycosis.

J Drugs Dermatol. 2017;16(10):1016-1021.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies.

BACKGROUND: Onychomycosis, a fungal nail infection, can impact quality of life. OBJECTIVE: We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis. METHODS: In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. RESULTS: Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle (P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). LIMITATIONS: Duration of follow-up is a limitation. CONCLUSION: Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.

Treatments of tinea pedis.

The severity of tinea pedis infection determines the course of treatment required. Mild infections may be resolved using a topical agent. More severe presentations (eg, dermatophytosis complex) may require treatment that eliminates the bacterial and fungal infection. Some topical monotherapies may exhibit both antifungal and antibacterial activity. In other instances, it may be necessary to combine an antifungal agent with an antibacterial agent. If inflammation is present, an agent with known anti-inflammatory action may need to be used. The chronic presentation of tinea pedis (dry type) sometimes does not respond well to topical therapy. In such instances, systemic antifungal therapy is required to ensure that adequate concentrations of the therapeutic agent are present at the site of infection.

The prevalence of dermatophyte infection in patients infected with human immunodeficiency virus.

BACKGROUND: It is not known whether human immunodeficiency virus (HIV) infection is associated with an increased susceptibility to dermatophytes. METHODS: In this study, we determined the prevalence of cutaneous fungal infection in a cohort of HIV-infected patients and HIV-negative controls, and examined the factors associated with an increased risk of infection. RESULTS: Using a multiple regression analysis, we found that the strongest independent predictor of cutaneous fungal infection in both groups was a self-reported history of homosexual sex. There was no relationship between HIV infection or reduced CD4 count and the prevalence of dermatophyte infection. CONCLUSIONS: HIV infection is not independently associated with an increased risk of cutaneous fungal disease.

The safety and efficacy of ciclopirox olamine for the treatment of seborrheic dermatitis.

Ciclopirox olamine is a synthetic hydroxypiridone derived, broad spectrum, antifungal agent which has been used effectively to treat seborrheic dermatitis. Seborrheic dermatitis is a chronic dermatosis, more common in men than women, which usually occurs in sites dense with sebaceous glands in the form of mild inflammatory desquamate erythema. Treatment modalities for seborrheic dermatitis include keratolytic agents, corticosteroids and antifungal agents. Due to its antimycotic and anti-inflammatory activities, ciclopirox olamine is established as an effective treatment for this condition.

Rapid response of Trichophyton tonsurans-induced onychomycosis after treatment with terbinafine.

We describe an 8-year-old Hispanic female who presented with distal subungual onychomycosis and tinea capitis. Both foci of infection yielded Trichophyton tonsurans upon culture, and were clinically and mycologically cured with terbinafine 125 mg, once daily for 1 week [DOSAGE ERROR CORRECTED]. This aspect of treatment with terbinafine has not previously been reported.

Ciclopirox gel for seborrheic dermatitis of the scalp.

BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder that usually occurs in patients with pre-existing seborrhea. The etiology of seborrheic dermatitis is uncertain. Typically, sites dense with sebaceous glands support growth of the lipophilic yeast Malassezia furfur. Ciclopirox (Loprox) gel is a hydroxypyridone, broad-spectrum antifungal agent proven effective against the yeast M. furfur. OBJECTIVE: A multicenter, randomized, double-blind, vehicle controlled study of 178 subjects evaluated the efficacy of ciclopirox gel in treating seborrheic dermatitis of the scalp. METHODS: One hundred and seventy-eight subjects were randomized to apply either ciclopirox gel 0.77% twice daily, or vehicle twice daily for 28 days. Subjects' signs and symptoms of severity (erythema, scaling, pruritus and burning) were rated on a scale of 0-3 (none to severe); for inclusion, a minimum score of 4, for the sum of the individual ratings was required. Efficacy evaluations were performed at baseline, days 4, 8, 15, 22, 29, and at end-point (final visit, up to day 33). The primary efficacy variable was clinical response assessed by a global improvement, based on a scale of 0-5 (100% clearance to flare of treatment area). Changes in signs/symptoms severity scores within the target lesion were also evaluated. RESULTS: Global evaluation scores demonstrated that significantly more ciclopirox-treated subjects achieved over 75% improvement compared with vehicle at days 22, 29, and endpoint (P < 0.01). Change-from-baseline mean score for total signs and symptoms was significantly greater in ciclopirox subjects compared with vehicle subjects at the same time points as above (P < 0.001), as well as day 15 (P < 0.01). Twenty-nine percent of subjects rated ciclopirox as having excellent cosmetic acceptability. There were only mild adverse events, with the most common being burning sensation in 13% of ciclopirox subjects and 9% of vehicle subjects. CONCLUSION: Ciclopirox gel is effective and safe in the treatment of seborrheic dermatitis of the scalp.

Terbinafine in the treatment of Trichophyton tinea capitis: a randomized, double-blind, parallel-group, duration-finding study.

OBJECTIVES: Terbinafine has been shown to be effective in tinea capitis, using different treatment durations. However, no direct comparison of treatment duration has previously been investigated. This randomized, double-blind, parallel-group, multicenter study was designed to assess the effect of terbinafine treatment duration on the outcome of Trichophyton tinea capitis in a North American population. METHODS: A total of 176 patients with a clinical diagnosis of tinea capitis were enrolled in this study and treated with oral terbinafine (3-6 mg/kg/d) for 1, 2, or 4 weeks. All patients were to be followed until week 12. A total of 159 patients had culture-confirmed tinea capitis attributable to Trichophyton species and constituted the intent-to-treat population used for efficacy analysis (50, 55, and 54 patients in the 1-, 2-, and 4-week arms, respectively). RESULTS: At the end of study, effective treatment, defined as negative culture and low scores on signs and symptoms, was achieved in 56%, 69%, and 65% of patients who were treated with terbinafine for 1, 2, and 4 weeks, respectively. A negative culture was achieved in 60%, 76%, and 72%, respectively. Overall, the efficacy data showed that both the 2- and 4-week treatment regimens are clinically superior to the 1-week regimen. Terbinafine was well tolerated, and the incidence of adverse events showed no relationship to the duration of therapy. CONCLUSION: When efficacy, cost, and compliance are taken into consideration, 2 weeks of terbinafine therapy appears to be the optimal treatment duration for patients with Trichophyton tonsurans tinea capitis.

Ciclopirox gel in the treatment of patients with interdigital tinea pedis.

UNLABELLED: BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum. OBJECTIVE: Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement. METHODS: Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure). RESULTS: At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment. CONCLUSIONS: Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects.