Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation.

Azelaic acid (AzA), a nine-carbon dicarboxylic acid, is an agent for the topical treatment of acne. It has also been shown to be effective in rosacea; however, the mechanism of action has not been clarified. Because inflammation is a common feature of both conditions, we investigated the effects of azelaic acid on the inflammatory response of normal human keratinocytes to ultraviolet B light, which is a photosensitizer agent in rosacea. AzA, at 20 mM, a concentration achievable following topical application of a 15% gel, suppresses ultraviolet B light-induced interleukins-1beta, -6 and tumor necrosis factor-alpha mRNA expression and protein secretion. Mechanistically, azelaic acid significantly reduced the ultraviolet B light-induced nuclear translocation of nuclear factor kB p65 subunit and the phosphorylation of the p38 mitogen and stress-activated protein kinase. Moreover, as peroxisome proliferators-activated receptor gamma, (PPARgamma) which has a crucial role in the control of inflammation, is activated by fatty acids and products of lipid peroxidation, we further investigated the effect of azelaic acid on the expression of this nuclear receptor. AzA induced peroxisome proliferators-activated receptor-gamma mRNA and its transcriptional activity. The PPARgamma antagonist GW9662 abrogated the inhibitory effects of AzA on the UVB-induced pro-inflammatory cytokines release and on the cell proliferation. Our study provides new insights into the molecular mechanisms of the activity of azelaic acid and lands additional evidences for its therapeutic effects on inflammatory skin diseases, such as rosacea.

Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea.

BACKGROUND: Twice-daily azelaic acid (AzA) is the conventional regimen for papulopustular rosacea, but once-daily AzA may be equally effective, with greater convenience and dosing flexibility. In order to test this hypothesis, an exploratory study was conducted. METHODS: The evaluable efficacy population of this 12-week double-blind, parallel-group study included 72 patients and the population that was used to report safety results included 92 patients. Baseline characteristics were comparable between the once-daily and twice-daily study groups. Evaluations were performed at baseline and at weeks 4, 8, and 12. RESULTS: No significant difference was found between the once-daily and twice-daily groups at the end of study therapy in mean investigator global assessment (IGA) scores, treatment success, or treatment response. The mean number of inflammatory lesions, the intensity of erythema intensity, and the intensity of telangiectasia at treatment end were likewise not significantly different (P>.205 for all). More than 90% of subjects in each group rated cosmetic acceptability of this AzA gel as satisfactory or better. CONCLUSION: Based on these findings and those of prior studies, once-daily AzA 15% gel can therefore be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of AzA 15% gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist.

[Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies]. / 15% Azelainsäuregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien.

BACKGROUND: Topical measures are still the mainstay in the therapy of mild-to-moderate acne vulgaris. Azelaic acid 20% in a cream formulation has been established as an efficacious and safe topical drug for 15 years. A new non-alcoholic hydrogel formulation containing 15% azelaic acid was clinically tested against two standard drugs--5% benzoyl peroxide (BPO) and 1% clindamycin. PATIENTS AND METHODS: In two independent, randomized, blinded comparative trials 15% azelaic acid gel was clinically tested against 5% benzoyl peroxide (BPO) gel in 351 patients and against 1% clindamycin gel in 229 patients. The drugs were applied b.i.d. for 4 months. RESULTS: Azelaic acid 15% gel proved to be as effective as BPO and clindamycin with median % reduction of the inflamed lesion (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was well-tolerated, the side effects (local burning and irritation) were distinctly less than with BPO but more pronounced than with clindamycin. Despite these side effects, the treatment was well-accepted by the majority of patients. CONCLUSIONS: Azelaic acid gel is an effective topical monotherapy for mild-to-moderate acne vulgaris; its new gel form is an enrichment of acne therapy.

Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies.

BACKGROUND: Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed. OBJECTIVE: The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea. METHODS: Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2. RESULTS: Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported. CONCLUSION: The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea.