mometasone-furoate and Atrophy

Topics: Administration, Cutaneous; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Animals; Atrophy; Child; Child, Preschool; Clinical Trials as Topic; Controlled Clinical Trials as Topic; Cytokines; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Irritant; Double-Blind Method; Drug Eruptions; Drug Evaluation, Preclinical; Eczema; Female; Guinea Pigs; Humans; Infant; Langerhans Cells; Male; Mice; Middle Aged; Mometasone Furoate; Multicenter Studies as Topic; Pituitary-Adrenal System; Pregnadienediols; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Rats; Skin

Topical glucocorticoids are still among the dermatologicals most frequently used. This is due to their undebatable potency in inflammatory skin disease. Their use is limited by the fear of side effects both systemic and topical, especially skin atrophy. Hence, congeners with an increased benefit-risk ratio are urgently needed and research on new drugs no longer focuses on more active drugs but safer ones. Only recently, evidence has been forwarded that the goal is realistic. Some new glucocorticoids, especially the nonfluorinated double-ester type such as prednicarbate, appear promising. In fact, they seem to affect fibroblast growth in vitro as well as skin thickness in vivo less than equipotent conventional glucocorticoids. Pertinent findings in humans have been obtained with the use of ultrasound equipment. The relevant aspects of chemistry, pharmacology, clinical benefits, and toxicology of the various glucocorticoids old and new are reviewed, as are potential future alternatives.

Topics: Administration, Topical; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Dermatitis, Atopic; Glucocorticoids; Humans; Mometasone Furoate; Odds Ratio; Prednisolone; Pregnadienediols; Psoriasis; Skin

Currently, there are no accurate and simple methods available to measure this risk of atrophy in patients treated with topical glucocorticosteroids. In the present clinical trial, we validated a new score (Dermaphot(®) score) to assess the atrophogenic potential of glucocorticosteroids. 36 healthy adult volunteers were included in an investigator-initiated, blinded, randomized, intra-individual comparison, vehicle controlled multi-centre study. Subjects were treated in a randomized manner for 3 weeks with pimecrolimus cream 1 %, mometasone furoate (1 mg/g), clobetasol propionate 0.05 % and vehicle. In addition, ultrasound examination for skin thickness was performed. Data demonstrated a direct correlation of the achieved Dermaphot(®) score and the ultrasound thickness measurements. Our study shows that the Dermaphot(®) score can be used as a simple method to evaluate the atrophogenic potential of glucocorticosteroids. Respectively, we showed that the new score is an easy, valid and sensitive new tool for early detecting and quantifying even subclinical glucocorticosteroid-induced skin damage. We demonstrated that the score is able to differentiate the extent of skin atrophy (damage) after 3 weeks of topical glucocorticosteroid application with different levels of skin transparency and levels of telangiectasia.

Topics: Adult; Atrophy; Clobetasol; Female; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Reproducibility of Results; Severity of Illness Index; Skin; Tacrolimus; Telangiectasis; Young Adult

Topical glucocorticoids with improved benefit/risk ratio are of great interest in dermatology, but there are very few trials directly comparing the efficacy and side-effects of these new preparations. In our study the vasoconstrictor effect and side-effects of two of these new glucocorticoids were evaluated and blanching effect was determined by two-dimensional laser scanning.. In a randomised, double blind intra-individual comparative trial, 10 subjects were treated with various glucocorticoids or drug-free vehicle. The test drugs were mometasone furoate (MF), methylprednisolone aceponate (MP) and hydrocortisone (OH-C). The preparations were tested for a period of 3 weeks with occlusion on the flexor side of the forearm. Skin thickness and vasoconstriction were determined using 20 MHz ultrasound scanning, laser Doppler scanning (LDS) and chromometry.. No adverse effects were observed during the observation period. Only partial vasoconstriction occurred in most cases during the observation period. MP and MF produced maximal blanching between days 3 and 5 of treatment, while with OH-C clinically visible blanching did not occur. Ultrasound evaluation of skin thickness showed similar behaviour for all three steroids tested: there were no signs of skin atrophy in any of the cases. LDS evidenced hypoperfusion of a test area on the perfusion image in only a few patients and there were no significant differences between the steroids tested. On evaluation of vasoconstriction caused by the steroids tested using chromometry there was a significant difference between MF and OH-C on the L*a*b* scale (P < 0.005). Only at day 3 was a blanching effect caused by MP and MF demonstrable (a-value, P < 0.05).. In summary, the synthetic steroids MF and MP presented side-effects similar to those of OH-C but much greater vasoconstrictor effect; after an application period of over 5 days under occlusion a blanching effect in our model was not demonstrable by means of chromometry. Two-dimensional laser scanning offers no advantage in the evaluation of the blanching effect in comparison to one-dimensional laser fluxmetry (LDF).

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Atrophy; Female; Humans; Hydrocortisone; Laser-Doppler Flowmetry; Male; Methylprednisolone; Middle Aged; Mometasone Furoate; Pregnadienediols; Skin; Spectrophotometry; Ultrasonography; Vasoconstriction

Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Angiogenesis Inducing Agents; Anti-Inflammatory Agents; Atrophy; Biopsy; Blood Proteins; Chymases; Eosinophil Granule Proteins; Eosinophilia; Eosinophils; Epithelium; Female; Follow-Up Studies; Glucocorticoids; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Inflammation Mediators; Male; Mast Cells; Metaplasia; Middle Aged; Mometasone Furoate; Nasal Mucosa; Pregnadienediols; Rhinitis, Allergic, Perennial; Ribonucleases; Serine Endopeptidases; Single-Blind Method; Tryptases

Topical glucocorticoids still belong to the most important medications available in dermatotherapy. The clinical use of topical glucocorticoids, however, nowadays is limited by the fear of side-effects both systemic and local, especially skin atrophy. The purpose of this study was to assess the atrophogenicity potential of newly developed topical glucocorticoids which were said to show an increased benefit-risk ratio. The test preparations comprised mometasone furoate, the corresponding vehicle, prednicarbate and hydrocortisone. They were applied once or twice daily for 6 weeks in healthy volunteers. Skin thickness was assessed weekly by using high frequency pulsed ultrasound. Clinically, none of the volunteers showed any sign of overt skin atrophy. Skin thickness, however, was reduced to a certain extent with all trial preparations including the base preparation. As to be expected from previous experiments the results for hydrocortisone and prednicarbate did not differ significantly from the ones for the base preparation. Interestingly, the same applied to mometasone furoate. These findings, together with the other available data, give evidence of an increased benefit-risk ratio as compared to previous medium potent topical glucocorticoids. This might be of particular interest facing psoriasis vulgaris where an antiproliferative activity of a drug is needed.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Atrophy; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Ointments; Prednisolone; Pregnadienediols; Skin

The safety and efficacy of once daily application of mometasone furoate cream 0.1% was determined by comparison with twice daily applications of betamethasone dipropionate cream 0.05% in a single blind, dual centre, randomized study in patients with a variety of steroid-responsive inflammatory dermatoses, the most common of which was psoriasis. Morning plasma cortisol levels revealed little adrenal suppression in either of the two study groups and there was no significant difference between the two groups. Routine laboratory investigations showed no trends in values outside the normal ranges that were of clinical significance. Less skin atrophy was seen in the group treated with mometasone furoate. In comparison to the betamethasone dipropionate treated group, those treated with mometasone furoate exhibited only slight evidence of skin atrophy, and this was not observed before four to twelve weeks of treatment. Eighteen percent of patients using mometasone reported adverse reactions but all were of limited duration and did not persist despite continued application of the drug. Nine percent of patients using betamethasone dipropionate reported adverse effects. Both drugs were found to be highly effective with no significant difference between the two groups at the termination of the treatment period. Of importance is the fact that whilst mometasone furoate is found to be a highly effective treatment for a variety of steroid-responsive dermatoses, this drug has only a limited potential for production of local and systemic side effects. Thus, a high margin of safety can be expected for patients using this drug.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Atrophy; Betamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Single-Blind Method; Skin Diseases

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Atrophy; Female; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Ointments; Pregnadienediols; Psoriasis; Skin

Glucocorticoids (GCs) belong to the most widely used anti-inflammatory drugs at all. However, their topical use is limited by their side effect potential, with skin atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is of importance for drug development. Currently, the most frequently performed model in the base and pharmaceutical research is the hr/hr rat model of GC-induced skin atrophy that lasts for 19 days. In this study, we analysed statistically skin atrophy experiments retrospectively to ascertain (i) the earliest time-point, at which skin atrophy is significantly induced; and (ii) whether the differences between the GC treatment groups change until the end of the experiment. We show here that the treatment duration of rat skin atrophy models might be reduced to 5 days for economical and ethical reasons.

Topics: Animals; Anti-Inflammatory Agents; Atrophy; Clobetasol; Disease Models, Animal; Glucocorticoids; Linear Models; Methylprednisolone; Mometasone Furoate; Pregnadienediols; Rats; Rats, Hairless; Skin; Time Factors

Although introduced more than 50 years ago, topical glucocorticoids are still the first line therapy for many inflammatory skin disorders such as atopic eczema, contact dermatitis and many others. Recently, significant improvements have been made to optimize the ratio of desired to unwanted effects. While with early compounds such as triamcinolone, topical side effects such as skin atrophy and telangiectasias can be observed rather frequently, newer drugs such as methylprednisolone aceponate or mometasone furoate have a significantly improved therapeutic index. The present study compared these two modern topical glucocorticoids, which possess the highest therapeutic index currently found, in terms of nuclear receptor selectivity in vitro and induction of the most important local side effects (skin atrophy and telangiectasias) in a relevant rodent model in vivo. We demonstrate that methylprednisolone aceponate displays higher specificity in nuclear receptor binding compared with mometasone furoate. Methylprednisolone aceponate was also markedly superior in terms of minimizing induction of skin atrophy or telangiectasias when compared with mometasone furoate. Based on these observations, methylprednisolone aceponate is expected to have a greater therapeutic index as compared with mometasone furoate, at least in the test systems used here. The degree to which this observation may translate into a clinical setting requires confirmation.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Atrophy; Disease Models, Animal; Methylprednisolone; Mometasone Furoate; Pregnadienediols; Protein Binding; Rats; Rats, Mutant Strains; Rats, Nude; Rats, Wistar; Receptors, Androgen; Receptors, Cytoplasmic and Nuclear; Receptors, Mineralocorticoid; Receptors, Progesterone; Skin; Telangiectasis

Topics: Anti-Inflammatory Agents; Atrophy; Cortisone; Glucocorticoids; Humans; Methylprednisolone; Mometasone Furoate; Ointments; Pituitary-Adrenal System; Prednisolone; Pregnadienediols; Skin Diseases; Time Factors