Efficacy and safety of topical steroids in paediatric atopic dermatitis

Background Atopic dermatitis (AD) affects 10–15% of children in the USA and up to 20% of children in the UK. Topical corticosteroids are the mainstay of therapy to control acute flares of AD in both children and adults. Aim In paediatric patients, it is especially important to ensure that local application of a corticosteroid used is limited to the least amount needed to produce a therapeutic response, as children are particularly prone to systemic adverse effects of these agents. The development of newer corticosteroid molecules is aimed at achieving maximum activity and minimal unwanted side effects. Review Mometasone furoate (Elocon®), a medium potency topical corticosteroid, is the only topical steroid approved for use in children in the USA. Mometasone furoate undergoes biotransformation in the liver into three different metabolites with very little intrinsic activity. Local side effects are minimal, with an atrophogenic potential comparable with that of 1% hydrocortisone ointment, and the risk of adrenal suppression is low. In clinical trials including over 300 infants and children, once-daily 0.1% mometasone furoate was found to be statistically significantly more effective than twice-daily 1% or 2.5% hydrocortisone, twice-daily 0.05% alclometasone dipropionate and twice-daily 0.05% fluticasone propionate. Conclusion The once-daily regimen of mometasone furoate is also useful in promoting compliance and reducing the potential for adverse effects.     

Relative lack of systemic effects of mometasone furoate on Langerhans cells of mice after topical administration as compared with other glucocorticosteroids

The effects of topically applied mometasone furoate were compared with those of other glucocorticosteroids, in particular fluocinolone acetonide, in assays of murine epidermal Ia+ Langerhans cell density. No evidence of systemic effects, as determined by a decline in the density of Ia+ LC in distant sites, was detected after local topical applications (5 times a week) of mometasone furoate 0.001% for periods of up to 3 weeks. Other steroids, even in such very low concentrations, and mometasone furoate in higher concentrations, produced systemic effects on Ia+ LC when used for longer than 5 d. The recovery time of Ia+ Langerhans cells is significantly shorter after application of mometasone furoate than after fluocinolone acetonide. However, with both compounds, recovery occurred more rapidly after 3 weeks than after a 1- or 2-week interval of compound administration.     

SAFETY AND EFFICACY OF MOMETASONE FUROATE CREAM IN THE TREATMENT OF STEROID RESPONSIVE DERMATOSES

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.     

Topical fluticasone propionate: intervention and maintenance treatment options of atopic dermatitis based on a high therapeutic index

Fluticasone propionate (FP), a medium potent glucocorticoid (class III) of carbothioate nature with a favourable benefit/risk ratio, has emerged as a standard medication for the topical treatment of inflammatory skin disorders, in particular atopic dermatitis (AD). FP is available as a 0.05% cream and a 0.005% ointment formulation. The glucocorticoid is characterized by high lipophilicity, high affinity binding to the glucocorticoid receptor and a rapid hepatic biotransformation. Though skin blanching following topical application of FP surpasses that given with glucocorticoids of medium strength, clinical trials show a low potential of FP for local and systemic adverse effects. Even in paediatric patients with AD as well as in difficult-to-treat areas like face, eyelids and intertriginous areas, FP proved to be both effective and safe. Thus, the therapeutic effects of FP clearly outweigh the unwanted effects. Correspondingly, a therapeutic index of 2.0 can be attributed to this glucocorticoid. In this respect, topical FP does not differ from other topical glucocorticoids with increased benefit-to-risk ratio, e.g. prednicarbate, methylprednisolone aceponate and mometasone furoate. However, randomized controlled trials do not only support conventional intervention but also innovative maintenance treatment.     

Investigator-masked comparison of tazarotene gel q.d. plus mometasone furoate cream q.d. vs. mometasone furoate cream b.i.d. in the treatment of plaque psoriasis

Seventy‐three patients with stable plaque psoriasis entered an investigator‐masked trial comparing once‐daily tazarotene 0.1% gel plus once‐daily mometasone furoate 0.1% cream with twice‐daily mometasone furoate 0.1% cream. The aim of the study was to determine whether tazarotene and mometasone furoate act synergistically –‐ a previous study showed that tazarotene plus mometasone furoate offered greater efficacy than tazarotene alone, and this study investigated whether tazarotene plus mometasone furoate also offered greater efficacy than mometasone furoate alone. The patients had psoriasis affecting up to 20% of their total body surface area, with at least moderate plaque elevation. Washout periods were: 2 weeks for UVB phototherapy or topical antipsoriatic therapies; 4 weeks for psoralen plus UVA (PUVA) therapy or systemic antipsoriatic drugs other than retinoids; and 8 weeks for oral retinoids. All patients gave written informed consent and the study was conducted in compliance with the ethical standards of the governing institutional review boards and the Declaration of Helsinki. Patients were treated for up to 12 weeks. If they achieved clearance by week 4, or at least 50% global improvement by week 12, they were entered into the 12‐week no‐treatment follow‐up phase. Patients were evaluated every 4 weeks in terms of percentage global improvement, plaque elevation, scaling, erythema, and pruritus. They also rated the efficacy of their own treatment (as very effective, effective, neutral, ineffective, or less effective) and the duration of improvement in their psoriasis (as much better, better, somewhat better, indifferent, or worse than that achieved with other topical medications they had used in the past). The two regimens were compared by analysis of variance, with the last recorded score for any patient who discontinued prematurely (due to lack of efficacy, adverse events, or disease flare) being carried forward to all subsequent visits.     

0.05%卤米松乳膏治疗皮炎湿疹类皮肤病多中心、随机对照、开放研究

目的观察0.05%卤米松乳膏治疗皮炎湿疹类皮肤病的疗效和安全性,并与0.1%糠酸莫米松乳膏进行比较。方法采用多中心、随机、开放试验,对92例亚急性湿疹和神经性皮炎患者外用0.05%卤米松乳膏或0.1%糠酸莫米松乳膏进行治疗,观察记录患者的临床表现和治疗反应。结果0.05%卤米松乳膏临床疗效优于0.1%糠酸莫米松乳膏,有效率分别为91.3%和71.7%(P<0.05),治疗指数分别为86.79%和74.37%(P<0.05)。结论0.05%卤米松乳膏治疗亚急性湿疹和神经性皮炎效果好,不良反应轻。     

Optimizing treatment with topical tazarotene

Tazarotene is a receptor-selective retinoid, which is efficacious in the treatment of patients with psoriasis, acne vulgaris, and photoaging. It normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has anti-inflammatory effects. Clinical studies have shown that tazarotene 0.1% gel has greater comedolytic activity than tretinoin (Retin-A 0.025% gel, Retin-A Micro 0.1%) and adapalene (Differin) 0.1% gel. Although it is efficacious as monotherapy, tazarotene is more commonly used as part of combination therapy with a topical antibacterial in patients with acne vulgaris, and with a mid- or high-potency topical corticosteroid or with phototherapy in patients with psoriasis. Combination therapy enhances efficacy and tolerability. Tazarotene 0.1% gel, used in combination with mometasone furoate 0.1% cream, was shown in psoriasis clinical trials to be more efficacious than calcipotriene (calcipotriol) ointment used twice daily, or mometasone furoate 0.1% cream used twice daily. Use of tazarotene in conjunction with broad band UVB, narrow band UVB or bath psoralens + UVA (PUVA) results in greater efficacy than with phototherapy alone. Tazarotene should not be administered during pregnancy or in women who are not practicing adequate contraception. Adverse events consist primarily of irritation, peeling, erythema, dryness, burning, and itching. They are most common during the first 1-2 weeks of therapy and can be minimized with use of the cream formulation, alternate day application, short contact therapy, mild cleansers, and combination therapy.     

丁酸氢化可的松软膏治疗儿童异位性皮炎临床疗效观察

目的:评价丁酸氢化可的松软膏治疗儿童异位性皮炎的临床疗效。方法:采用自身对照,治疗侧用丁酸氢化可的松软膏;对照侧用0.1％糠酸莫米松霜。结果:共观察了46例异位性皮炎患儿,丁酸氢化可的松软膏的有效率为84.78%,0.1％糠酸莫米松霜的有效率为91.30％,二者差异无显著性(x2=0.93,P>0.05)。二组均未观察到明显的不良反应。结论:丁酸氢化可的松软膏是一种高效、安全的外用皮质类固醇激素制剂,可以应用于治疗儿童异位性皮炎。     

外用苯烯莫德对特应性皮炎样小鼠的治疗作用

目的：评价外用苯烯莫德对卡泊三醇（MC903）诱导的特应性皮炎小鼠模型的治疗作用。方法：36只BALB/c小鼠，6只作为空白对照，30只给予MC903诱导特应性皮炎后再随机分为基质组、0.5%苯烯莫德组、1.0%苯烯莫德组、0.1%糠酸莫米松组和0.1%他克莫司组，治疗前后测量皮肤厚度、经皮水丢失（TEWL）、皮损内CD4+T细胞、胸腺基质淋巴细胞生成素（TSLP）蛋白表达。结果：0.5%和1.0%苯烯莫德乳膏组皮损评分、耳部皮肤厚度、TEWL、皮损内CD4+T细胞及TSLP蛋白水平较基质组均显著降低（P<0.05），1.0%苯烯莫德组疗效优于0.5%苯烯莫德组和他克莫司组（P<0.05），与糠酸莫米松组差异无显著性（P>0.05）。结论：外用苯烯莫德乳膏可减轻特应性皮炎样小鼠局部炎症反应。     

0.05%地奈德乳膏治疗三种常见皮肤病的疗效观察

目的评价0.05%地奈德乳膏治疗特应性皮炎、脂溢性皮炎及寻常性银屑病的临床疗效及安全性。方法采用开放式研究。分别应用0.05%地奈德、1%丁酸氢化可的松及0.1%糠酸莫米松乳膏治疗特应性皮炎、脂溢性皮炎及寻常性银屑病。对患者治疗前后红斑、糜烂、浸润、丘疹、渗出/结痂、瘙痒及皮损面积的总积分进行评价。结果治疗2周后,地奈德组的临床疗效明显优于丁酸氢化可的松组,差异有显著性(P<0.05),两组均未见明显不良反应;地奈德组的疗效与糠酸莫米松组相当(P>0.05),但后者有1例出现瘙痒,1例出现红斑加重。结论应用0.05%地奈德乳膏治疗特应性皮炎、脂溢性皮炎及寻常性银屑病疗效可靠,临床使用安全。     

Unique immunobullous disease in a child with a predominantly IgA response to three desmosomal proteins

Chronic hand eczema can be incapacitating, and there is little knowledge of the efficacy and safety of long-term treatment with topical corticosteroids. We compared the efficacy and safety of two different schedules for the treatment of chronic hand eczema with a potent topical corticosteroid, mometasone furoate. In a prospective, open, randomized trial, 120 patients with chronic hand eczema were treated daily with mometasone furoate fatty cream until the dermatitis cleared or for a maximum of 9 weeks. Those who cleared were randomized to treatment for up to 36 weeks with mometasone furoate on Sunday, Tuesday and Thursday (group A), mometasone furoate on Saturday and Sunday (group B) or no further corticosteroid treatment (group C). In the event of relapse, patients were permitted daily treatment with mometasone furoate for 3 weeks on two separate occasions. For 50 of 106 randomized patients, daily treatment for 3 weeks controlled their dermatitis; 29 needed 6 weeks and 27 needed 9 weeks of treatment. During the maintenance phase, 29 of 35 (83%) in group A, 25 of 37 (68%) in group B and nine of 34 (26%) in group C had no recurrences (P = 0.001, chi2-test). Side-effects were minimal. It is concluded that long-term, intermittent treatment of chronic hand eczema with mometasone furoate fatty cream is effective and safe.     

Sensitization studies with mometasone furoate, tixocortol pivalate, and budesonide in the guinea pig

Mometasone furoate is a new corticosteroid, synthesized to have an improved ratio of anti-inflammatory potential to adverse effects. The guinea pig maximization test was used to determine the sensitizing capacity of mometasone furoate, and also to investigate cross-reaction patterns in animals sensitized to tixocortol pivalate and budesonide, respectively. Tixocortol pivalate was shown to be a sensitizer in the guinea pig, but cross-reactions to other tested corticosteroids wore not observed. Furthermore, no sensitizing capacity could be demonstrated for budesonide or mometasone furoate.     

外用川百止痒洗剂联合0.1%糠酸莫米松乳膏治疗湿疹临床研究

目的观察川百止痒洗剂联合0.1%糠酸莫米松乳膏治疗湿疹的有效性与安全性。方法采用随机、单盲、平行对照的方法对63例湿疹患者应用川百止痒洗剂联合0.1%糠酸莫米松乳膏外用治疗,同时设立对照组64例单独外用0.1%糠酸莫米松乳膏,治疗12天后评价疗效,并进行皮肤病生活质量指数(dermatology life quality index,DLQI)问卷调查。结果试验组总有效率为87.30%,与对照组70.31%相比有统计学差异(P<0.01);DLQI总分两组均下降,但无统计学差异(P=0.8775);试验组和对照组发生局部刺激反应分别为6.3%和7.8%,无统计学差异(Fisher校正χ2检验P=1.0000)。结论川百止痒洗剂联合0.1%糠酸莫米松乳膏治疗湿疹较为有效、安全。     

Use of adapalene in alopecia areata: Efficacy and safety of mometasone furoate 0.1% cream versus combination of mometasone furoate 0.1% cream and adapalene 0.1% gel in alopecia areata

Alopecia areata (AA) is an autoimmune disease characterized by non‐cicatricial hair loss. No definitive therapy currently exists for AA. To compared the efficacy and safety of the mometasone furoate 0.1% cream alone with the mometasone furoate 0.1% cream plus adapalene 0.1% gel in treatment of AA. Twenty patients with AA and with mean age of 27.4 ± 9.2 years were enrolled. Patches with a diameter of < 5 cm were treated with mometasone furate 0.1% cream (M), and patches with a diameter of ≥5 cm were treated with mometasone furate 0.1% cream plus adapalene 0.1% gel (M + D) for a period of 12 weeks. Hair regrowth was evaluated using a Re‐growth score (RGS). Mean RGSs of M + D group were higher than M group for 4th week (2.60 vs. 1.45); 8th week (3.85 vs. 2.40) and 12th week (4.40 vs. 3.30). Mean percentages of hair re‐growth in M + D group were statistically higher than M group for 4th (50.2% vs. 23.5%), 8th (78.5% vs. 50.7%), and 12th week (90.5% vs. 71%). Study revealed the efficacy and safety of adapalene and mometasone furoate combination in AA. Adapalene can be used as a new therapeutic modality in AA.     

Mometasone furoate 0.1% and salicylic acid 5% vs. mometasone furoate 0.1% as sequential local therapy in psoriasis vulgaris

Background and objective  Treatment in psoriasis vulgaris continues to unmet needs in terms of efficacy, quality of life and costs. Patients with moderate forms of psoriasis are using topical corticosteroids as first-line therapy and patients with severe forms also use this therapy. Optimization of this treatment is made by the use of combination drugs or by the sequential or rotational therapies. A multicentric clinical study was performed to measure the efficiency of mometasone furoate 0.1% and salicylic acid 5% and mometasone furoate 0.1% as sequential local therapy in psoriasis.
Methods  This was a randomized, multicentre trial with two patient groups receiving active treatment. The study group ( N  = 184) received mometasone furoate 0.1% and salicylic acid 5% for the first 7 days of treatment, and in the following 14 days, the patients used mometasone furoate 0.1%. The second group ( N  = 176) was treated with mometasone furoate 0.1% for 21 consecutive days. Psoriasis Area Severity Index (PASI) score and Dermatology Life Quality Index (DLQI) were calculated.
Results  After the first week of treatment in the study group, the reduction of PASI score was 44%, statistically significant greater than the reduction of PASI score in the second group (37%). Quality of life estimated by DLQI indicated significant lower values in the first (study) group.
Conclusion  The sequential treatment mometasone furoate 0.1% and salicylic acid 5% followed by mometasone furoate 0.1% proves to be efficient, safe and an excellent option for the following sequence: in-patient and out-patient.

Conflict of Interest

None declared.     

Comparative potency of formulations of mometasone furoate in terms of inhibition of 'PIRHR' in the forearm skin of normal human subjects measured with laser doppler velocimetry

BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR) in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF) as measured with laser doppler velocimetry (LDV). RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2 min) of PIRHR was ( Mean +/- SEM ), Control = 213.52 +/- 11.80, Placebo = 209.77 +/- 19.31, Formulation A = 119.83 +/- 13.71, Formulation C = 53.67 +/- 4.85 and Formulation D = 111.46 +/- 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.     

Longitudinal in vivo tracking of adverse effects following topical steroid treatment

Topical steroids are known for their anti‐inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two‐photon excitation fluorescence microscopy (TPEF) of reduced nicotinamide adenine dinucleotide (NADH) to visualize the epidermal cell layers and second harmonic generation (SHG) microscopy to identify collagen in the dermis, these processes can be studied at the cellular level. Fluorescence lifetime imaging microscopy (FLIM) is also utilized to image intracellular NADH levels to obtain molecular information regarding metabolic activity following steroid treatment. In this study, fluticasone propionate (FP)‐treated, mometasone furoate (MF)‐treated and untreated animals were imaged longitudinally using a custom‐built multimodal optical microscope. Prolonged steroid treatment over the course of 21 days is shown to result in a significant increase in mean fluorescence lifetime of NADH, suggesting a faster rate of maturation of epidermal keratinocytes. Alterations to collagen organization and the structural microenvironment are also observed. These results give insight into the structural and biochemical processes of skin atrophy associated with prolonged steroid treatment.     

Decrease in enkephalin levels in psoriatic lesions after calcipotriol and mometasone furoate treatment

BACKGROUND: Enkephalins are opioid peptides that can modulate immune responses and inflammatory processes. Furthermore, they inhibit keratinocyte proliferation/differentiation in vitro. Previously, we have shown that enkephalins are present in increased amounts in lesional psoriasis. OBJECTIVE: To determine the effect of topical treatment with the vitamin D analogue calcipotriol and the corticosteroid mometasone furoate on the level of methionine-enkephalin (enk) in psoriatic lesions. METHODS: Twelve psoriatic patients were treated with calcipotriol and mometasone furoate for 14 days without or with hydrocolloid occlusion. Keratome biopsies were obtained from treated and untreated skin, and the extracted enk was quantified by radioimmunoassay. Furthermore, punch biopsies were obtained for immunohistochemical analysis. RESULTS: Clinically, both calcipotriol and mometasone furoate improved psoriasis to the same degree, the effects being more pronounced after occlusion. Histologically, treatment with mometasone furoate without occlusion decreased both the epidermal thickness/parakeratosis and the number of dermal immunocompetent cells (CD3- and CD68-positive cells). In contrast, treatment with calcipotriol without occlusion reduced the epidermal thickness and the degree of parakeratosis but decreased the number of CD3- and CD68-positive cells only slightly. The mean enk level was decreased by 26 and 86% by calcipotriol without and with occlusion and by 16 and 63% by mometasone furoate without and with occlusion, respectively. The decreases in the enk levels corresponded to the degree of clinical improvement but not to the histological changes. CONCLUSION: The increased levels of enk in psoriatic lesions are reduced in parallel with the clinical improvement induced by a topical vitamin D analogue and a corticosteroid. Because enkephalins can modulate epidermal differentiation and inflammatory processes, the findings indicate that enkephalins may play a role in the pathogenesis of psoriasis.     

The Clinical Efficacy of Mometasone Furoate in Multi-Lamellar Emulsion for Eczema: A Double-blinded Crossover Study

Background

Topical application of corticosteroids also has an influence on skin barrier impairment. Physiological lipid mixtures, such as multi-lamellar emulsion (MLE) containing a natural lipid component leads to effective recovery of the barrier function.

Objective

The purpose of this study was to conduct an evaluation of the therapeutic efficacy and skin barrier protection of topical mometasone furoate in MLE.

Methods

A multi-center randomized, double-blind, controlled study was performed to assess the efficacy and safety of mometasone furoate cream in MLE for Korean patients with eczema. The study group included 175 patients with eczema, who applied either mometasone furoate in MLE cream or methylprednisolone aceponate cream for 2 weeks. Treatment efficacy was evaluated using the physician''s global assessment of clinical response (PGA), trans-epidermal water loss (TEWL), and visual analogue scale (VAS) for pruritus. Patients were evaluated using these indices at days 4, 8, and 15.

Results

Comparison of PGA score, TEWL, and VAS score at baseline with those at days 4, 8, and 15 of treatment showed a significant improvement in both groups. Patients who applied mometasone furoate in MLE (74.8%) showed better results (p<0.05) than those who applied methylprednisolone aceponate (47.8%). The TEWL improvement ratio was higher in the mometasone furoate in MLE group than that in the methylprednisolone aceponate group, and VAS improvement was also better in the mometasone furoate in MLE group.

Conclusion

Mometasone furoate in MLE has a better therapeutic efficacy as well as less skin barrier impairment than methylprednisolone aceponate.     

Mometasone furoate ointment and cream 0.1 percent in treatment of psoriasis: comparison with ointment and cream formulations of fluocinolone acetonide 0.025 percent and triamcinolone acetonide 0.1 percent

Mometasone furoate (Elocon) is a newly formulated and unique medium-potency synthetic 17-heterocyclic corticosteroid. The efficacy and safety of the ointment and cream formulations (0.1 percent) of the corticosteroid, administered once daily, were compared with those of the ointment and cream formulations of fluocinolone acetonide 0.025 percent administered three times daily and triamcinolone acetonide 0.1 percent administered twice daily in four multicenter clinical studies. They were conducted involving psoriasis patients with chronic and moderate to severe disease. Evaluation of change in disease sign scores indicated that mometasone ointment, applied once daily, was significantly more effective (P less than 0.01) than fluocinolone ointment, applied three times daily, and triamcinolone ointment, applied twice daily. The cream formulation of mometasone was significantly more effective (p less than 0.001) than fluocinolone cream, applied three times daily, and equivalent to triamcinolone cream, applied twice daily. The incidence of local adverse experiences following treatment with the ointment or cream formulations of mometasone was minimal. Mometasone ointment and cream provide a highly effective once-a-day treatment for moderate to severe psoriasis with minimal risk of side effects.