Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapy.

BACKGROUND: Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders and its prevalence rises with age. As onychomycosis is an important medical disorder affecting both patient's health and quality of life, it requires prompt and effective treatment. OBJECTIVE: Topical antifungal nail lacquers have been formulated to provide efficient delivery to the nail unit. As both amorolfine and ciclopirox have proved useful as monotherapy for onychomycosis that does not involve the nail matrix area, the purpose of this article is to check if, when combined with oral agents, the effectiveness and scope of treatment can be improved further. METHODS: Combining data for mycological cure with clinical success (nail morphology) provides a more exacting efficacy measure. RESULTS: Clinical investigations have shown that the combination of oral therapies with antifungal nail lacquer can confer considerable advantage over monotherapy with either drug type. CONCLUSION: The improved effectiveness and economic advantages of combined topical/oral therapies benefit both patients and health providers; these treatment regimens therefore have an important role to play in the modern management of onychomycosis.

The use of tetracyclines for the treatment of sarcoidosis.

BACKGROUND: To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. OBSERVATIONS: Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. CONCLUSIONS: These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.

[Renal function during long-term cyclosporin treatment of psoriasis]. / Tolérance rénale de la ciclosporine au long cours dans le psoriasis.

INTRODUCTION: The goal of this retrospective study was to evaluate the effects of cyclosporin A on renal function in patients treated for five years or more. PATIENTS AND METHODS: Two hundred twenty-four psoriasis patients were treated with cyclosporin at St. Louis Hospital, in Paris, from 1988 to 1997. Eleven patients (5 p. 100 of the total) took cyclosporin for at least five years. Nine case histories were available for the analysis. RESULTS: The group studied consisted of eight men and one woman, ranging in age from 28 to 48 with an average age of 38 years. The average cyclosporin dosage was 3.6 mg/kg/day (2.0-5.0 mg/kg/day). The changes in renal function were not significant as compared to the baseline level. The patients did not show persistent increases of serum creatinine more than 30 p. 100 of the pre-treatment value. Two patients had to discontinue treatment after 6 years because of a 20 p. 100 decrease in glomerular filtration rate. DISCUSSION: Previous studies have shown that cyclosporin A is not a suitable long-term continuous monotherapy for psoriasis. However, with precise and regular monitoring of kidney function, a minority of patients can benefit from prolonged treatment without experiencing side effects.