Bibliography

This page lists the references cited concerning Finacea® and Skinoren® in alphabetical order.

  • Berg M, Liden S. An epidemiological study of rosacea. Acta Derm Venereol 1989;69(5):419-23
  • In a non-selected population of 809 office employees (454 women and 355 men) 81 persons were diagnosed as having rosacea, giving a prevalence of 10% (women 14%, men 5%). The rosacea group was compared with the rest of the study population. Most of the cases were rather mild. The rosacea was of an erythematotelangiectatic type in 81% of the cases and of a papulopustular type in 19%. Unilateral lesions were found in 11 subjects (14%). Only 17% of those with rosacea were impaired by sunlight, whereas 26% improved. In the rosacea group, 27% were found to suffer from migraine and 42% from a tendency to flush, compared with 13% (p less than 0.001) and 16% (p less than 0.001) respectively in the comparison group. Flushing and the regulatory mechanism of the blood vessels thus seem to be of importance in the pathogenesis of rosacea. Individuals with good pigmentation ability showed a tendency to a decreased occurrence of rosacea. The frequency of eye complaints was the same in the two groups.
  • Elewski BE, Fleischer AB Jr, Pariser DM. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol 2003 Nov;139(11):1444-50
  • OBJECTIVE: To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea. DESIGN: Multicenter, double-blind, randomized, parallel-group study. SETTING: Thirteen US centers. PATIENTS: A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia. INTERVENTIONS: Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks. MAIN OUTCOME MEASURES: Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings. RESULTS: Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group. CONCLUSION: Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).
  • Carmichael AS et al.: Topical azelaic acid in the treatment of rosacea. J Dermatol Treat 1993;4(1):19-24.
  • Azelaic acid is now an established therapeutic agent for acne vulgaris, where its antibacterial and comedolytic activity is responsible in the main for its beneficial effects. In this report we describe the results of a single-centre double-blind controlled contralateral split-face study of the effects of 20% azelaic acid cream in patients with rosacea. The study was designed as a randomized half-face com­parison between a 20% azelaic acid cream preparation and its identical-appearing vehicle as placebo. Patients were treated over a 9-week period and reviewed 4 weeks after the end of the treatment period. Both 'sides' showed a reduction in papules, pustules and erythema, although the degree of improvement was superior on the azelaic acid-treated sides. This was also the case for the subjective overall evaluation used. No effect on telangiectasia was recorded. Minor degrees of skin irritation were recorded on both treatment sides in nearly equal numbers, although in the first 3 weeks this was more pronounced on the azelaic acid-treated sides. No serious adverse effects were experienced and no patient had to stop treatment prematurely on this account.
  • Cunliffe WJ: The Clinical Efficacy of Azelaic Acid in the Treatment of Acne. Rev Contemp Pharmacother 1993;4:433-439
  • Azelaic acid, a relatively new treatment for mild-to-moderate acne vulgaris, affects both P. acnes population and comedone formation, resulting in a reduction of both inflamed and non-inflamed lesions. Comparative studies clearly show azelaic acid to be better than placebo and similar to standard topical therapies such as retinoic acid which works predominantly against non-inflamed lesions, and benzoyl peroxide and topical erythromycin which are reputed to be more effective on inflamed lesions. The data of a 6-months study showed azelaic acid and oral tetracycline to be of similar efficacy. Not surprisingly, topical azelaic acid is not as effective as oral isotretinoin. The rate of onset of benefit of azelaic acid is gradual, with most studies showing an improvement of the order of 60% in both inflamed and non-inflamed lesions by the end of 6 months treatment. One of the major benefits of azelaic acid relates to its favorable adverse event profile. Most topical therapies for acne produce a significant degree of erythema and irritation and these side effects can be a significant clinical problem; azelaic acid, on the other hand, produces less erythema, scaling and itching than is noted with benzoyl peroxide or topical retinoic acid. A further benefit over certain topical preparations, such as benzoyl peroxide, is that it does not bleach clothes, and in contrast to antibiotics it will not be associated with the development of bacterial resistance. Azelaic acid is a useful addition to the armamentarium of topical therapies for mild-to-moderate acne.
  • Holland KT et al.: The effect of azelaic acid on cutaneous bacteria. J Dermatol Treat 1989;1:17-19
  • The effects of zinc sulphate and azelaic acid on 5 alpha-reductase activity in human skin were studied using an in vitro assay with 1,2[3H]-testosterone as substrate. When added at concentrations of 3 or 9 mmol/l, zinc was a potent inhibitor of 5 alpha-reductase activity. At high concentrations, zinc could completely inhibit the enzyme activity. Azelaic acid was also a potent inhibitor of 5 alpha-reductase; inhibition was detectable at concentrations as low as 0.2 mmol/l and was complete at 3 mmol/l. An additive effect of the two inhibitors was observed. Vitamin B6 potentiated the inhibitory effect of zinc, but not of azelaic acid, suggesting that two different mechanisms are involved. When the three substances were added together at very low concentrations which had been shown to be ineffective alone, 90% inhibition of 5 alpha-reductase activity was obtained. If this inhibition is confirmed in vivo, zinc sulphate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin.
  • Kligman AM, Jansen T, Plewig G : Acne and Rosacea; Springer Verlag, Heidelberg 2000
  • Mayer-da-Silva A, Gollnick H, Detmar M, Gassmuller J, Parry A, Muller R, Orfanos CE. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh) 1989;143:20-30

    The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.
  • Nazarro-Porro M et al.: Effects of dicarboxylic acids on lentigo maligna. J Invest Dermatol 1979;72:296-305
  • Wilkin J, Dahl M, Detmar M, Drake L, Feinstein A, Odom R, Powell F. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol 2002 Apr;46(4):584-7
  • Thiboutot D, Thieroff-Ekerdt R, Graupe K. Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. J Am Acad Dermatol 2003 Jun;48(6):836-45

Additional studies

For more information