Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

Limitation of the deterioration of lipid parameters by a standardized garlic-ginkgo combination product. A multicenter placebo-controlled double-blind study.

The efficacy of a garlic-ginkgo combination product (Allium plus) was analyzed in a randomized placebo-controlled double-blind study under extreme dietary conditions. The Christmas/New Year's season was chosen for this 2 months lasting investigation analyzing whether the known cholesterol lowering effect of garlic was even effective during the period of the year with the most cholesterol-rich meals. 43 patients with elevated total cholesterol levels ranging between 230-390 mg/dl completed the study. There were no significant changes of the total cholesterol values in both treatment groups. Nevertheless the analysis of improvement or deterioration of total cholesterol values revealed a clear difference between verum and placebo. 20% of the patients in the placebo group showed an improvement of their total cholesterol level, while there was a significant greater improvement rate of 35% in the verum group (p < 0.05). The responders of the verum group showed a reduction in the total cholesterol values from 298.5 +/- 53.8 to 293.0 +/- 56.4 mg/dl after 1 month and a total reduction of 10.4% after 2 months to 267.6 +/- 44.4 mg/dl. The difference after 2 months of treatment was significantly different from the starting value (p < 0.05). After the 2 months treatment phase there was a 2 weeks wash-out period. During this period the total cholesterol value returned to 293.5 +/- 90.1 mg/dl showing the effectiveness of garlic treatment, but indicating the need for a continuous long-term therapy.

Treatment of onychomycosis with terbinafine.

An open multicentre trial was conducted by 40 dermatologists in Switzerland involving 188 patients with onychomycosis of either the toenails or fingernails. Of these patients, 145 who had positive microscopy and culture of dermatophyte infection were evaluable: of the dermatophytes identified at the initial visit, 80% were Trichophyton rubrum and 12.4% were T. mentagrophytes. Only the most affected nail was evaluated during the observation period. Daily dosage was 250 mg of terbinafine (Lamisil) orally for up to 6 months. The cure rate (negative microscopy and culture) at the end of treatment was 77% for toenails and 100% for fingernails. A follow-up investigation was made 6 months after the end of treatment: of the 88 patients examined with onychomycosis of the toenail and the 14 with fingernail onychomycosis, 90.9% and 85.7%, respectively, remained free of recurrence. Of the 26 patients who had shown improvement, but not cure, by the end of the treatment period, 15 were clinically and mycologically cured at the time of the follow-up investigation. Terbinafine was generally well tolerated; the most frequent drug-related adverse events were mild-to-moderate gastrointestinal disturbances. Changes in liver or renal biochemical tests were not considered clinically relevant.