Tazarotene foam, 0.1%, for the treatment of acne

Introduction: Acne is a common skin condition of the pilosebaceous units that affects the young and old, ranges from moderate to severe and can be treated with an array of options. Topical retinoids are the initial treatment for acne due to their ability to treat comedones, the starting point of acne.

Areas covered: Tazarotene is a topical retinoid available as a cream, gel and foam. Tazarotene 0.1% foam was FDA approved in 2012 for the treatment of acne in patients ages ≥12 and is the first foam topical retinoid on the market. Phase I and III trials support the efficacy and safety of tazarotene foam for acne.

Expert opinion: The foam vehicles may increase compliance and satisfaction in some patients and as retinoids are commonly first line acne treatments, this new topical retinoid foam may be a useful option for some acne patients.     

Adverse events related to topical drug treatments for acne vulgaris

ABSTRACT

Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.

Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.

Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).     

Tolerability comparison of adapalene gel, 0.3% versus tazarotene cream, 0.05% in subjects with healthy skin

BACKGROUND: Topical retinoids, including adapalene and tazarotene, are a primary treatment choice for patients with acne. Adapalene is currently marketed in a 0.1% concentration in gel and cream formulation. A new gel containing a higher concentration (0.3%) of adapalene has been developed. In clinical studies, adapalene 0.1% concentration has proven to be better tolerated than other retinoids in skin treatment. However, the tolerability of adapalene gel 0.3% has yet to be compared to other topical retinoids. PURPOSE: The purpose of this study was to compare the local cutaneous tolerability of adapalene gel 0.3% once daily versus tazarotene cream 0.05% once daily. METHODS: Subjects reported to the investigative site each day Monday through Friday, cleansed the faced and then applied adapalene 0.3% gel to one side of the face and tazarotene 0.05% cream to the other in the presence of study personnel. For the weekends, subjects were instructed to apply the treatment at home according to the same procedure. Tolerability was assessed during each weekday visit. The study lasted for 3 weeks. RESULTS: Tolerability results for adapalene 0.3% gel and tazarotene 0.05% cream were statistically similar throughout the study. Investigator-assessed overall tolerability was in favor of adapalene at days 19 and 22 (P=.043). A cosmetic acceptability survey also showed results were better for adapalene 0.3% gel. CONCLUSION: Adapalene gel 0.3% is very well-tolerated with good cosmetic acceptability.     

Study results of benzoyl peroxide 5%/clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris

Combination therapy is the standard of care in the management of acne vulgaris. It is essential to treat as many aspects of acne pathogenesis as possible. Due to increasing insensitivity of Propionibacterium acnes to antibiotics, the concomitant use of other topical agents that exhibit other modes of antibacterial and anti-inflammatory activity is integral to the successful treatment of acne. The combination of topical benzoyl peroxide and clindamycin gel has been shown to be more effective than either agent alone. The addition of a topical retinoid may further enhance therapeutic results. This 12-week study evaluated the safety and efficacy of initial topical benzoyl peroxide 5%/clindamycin 1% gel as monotherapy and in combination with adapalene gel versus adapalene gel monotherapy in the management of acne.     

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris

Context and objective: Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris.

Materials and methods: The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded.

Results: Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p?<?0.01), as well as Clin 2% or AA 5% treatment groups (p?<?0.05 or p?<?0.01). The percentage of reduction in ASI in combination treated group (64.16?±?6.01) was significantly more than those in the Clin 2% (47.73?±?6.62, p?<?0.05) and 5% AA (32.46?±?5.27, p?<?0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p?<?0.01). Seven patients in AA-Clin group (incidence?=?22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients.

Discussion and conclusion: The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.     

Site-Specific Drug Delivery to Pilosebaceous Structures Using Polymeric Microspheres

In order to improve the therapeutic index of adapalene, a new drug under development for the treatment of acne, site-specific delivery to the hair follicles using 50:50 poly(DL-lactic-co-glycolic acid) microspheres as particulate carriers was investigated in vitro and in vivo. The percutaneous penetration pathway of the microspheres was shown to be dependent on their mean diameter. Thus, after topical application onto hairless rat or human skin, adapalene-loaded microspheres (5-µm diameter) were specifically targeted to the follicular ducts and did not penetrate via the stratum corneum. The in vitro release of adapalene from the microspheres into artificial sebum at 37°C was controlled and faster than the in vivo sebum excretion in humans. Aiming to reduce either the applied dose of drug or the frequency of administration, different formulations of adapalene-loaded microspheres were evaluated in vivo in the rhino mouse model. A dose-related comedolytic activity of topical formulations of adapalene-loaded microspheres was observed in this model. Furthermore, by applying a site-specific drug delivery system (0.1% adapalene) every other day or by administering a 10-fold less concentrated targeted formulation (0.01%) every day, a pharmacological activity equivalent to a daily application of an aqueous gel containing drug crystals (0.1% adapalene) was observed. Since an aqueous gel containing 10% adapalene-loaded microspheres was not irritating in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy. These results support the view that follicular drug targeting using 5-µm polymeric microspheres may represent a promising therapeutic approach for the treatment of pathologies associated with pilosebaceous units.     

In vivo antibacterial activity of Garcinia mangostana pericarp extract against methicillin-resistant Staphylococcus aureus in a mouse superficial skin infection model

Context: Garcinia mangostana Linn. (Guttiferae) (GM) pericarp has been shown to exhibit good in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); however, there is currently no available information regarding its in vivo antibacterial activity.

Objective: To examine in vivo antibacterial activity of G. mangostana extract against MRSA.

Materials and methods: GM pericarp was extracted by ethanol (GM-EtOH) and methanol (GM-MeOH). The crude extracts were examined for in vitro antibacterial activity against MRSA using broth microdilution assay. The in vivo antibacterial activity of 10% GM-EtOH against MRSA was determined in a tape stripping mouse model of superficial skin infection for 9 days by evaluating transepidermal water loss (TEWL) and performing colony counts from cultured swabs.

Results: GM-EtOH showed greater in vitro activity against MRSA than GM-MeOH in broth microdilution assay with minimum inhibitory concentration 17 versus 20?μg/mL and minimum bactericidal concentration 30 versus 35?μg/mL, respectively. The GM-EtOH (13.20?±?0.49%) contained α-mangostin more than the GM-MeOH (9.83?±?0.30%). In the tape stripping mouse model, 10% GM-EtOH reduced the number of MRSA colonies (0–1) recovered from infected wounds (>100 colonies) on the first day of treatment, restored TEWL to normal levels on the fourth day, and had completely healed the wounds by day 9.

Conclusion: GM-EtOH showed promising in vivo antibacterial activity against MRSA in a superficial skin infection model in mice. It is of interest to develop a topical formulation of GM-EtOH to further study its potential as a novel antibacterial agent.     

Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies

Acne vulgaris is an exceptionally common, chronic, and recurring disease. It involves multiple etiological factors including follicular hyperkeratinization, increased sebum production, Propionibacterium acnes proliferation, and inflammation. Presently, oral isotretinoin is the only single agent that is effective against all 4 major pathophysiologic features. However, this drug is also responsible for several serious side effects, including teratogenicity. Therefore, it should be used in only the most severe cases and alternative treatment approaches for inflammatory acne, such as initial combination therapy, should be considered first. Combination therapy in inflammatory acne simultaneously targets multiple pathogenic factors. Current guidelines recommend early initiation of combination therapy with a topical retinoid and antimicrobials for mild to moderate inflammatory acne and topical retinoids with oral antibiotics (with or without the use of benzoyl peroxide) for moderate to severe cases of acne, followed by maintenance therapy with topical retinoids. This review evaluates the rationale and clinical evidence for the use of adapalene in combination therapy for inflammatory acne.     

黄柏胶囊联合异维A酸红霉素凝胶治疗轻中度痤疮的疗效观察

目的 探讨黄柏胶囊联合异维A酸红霉素凝胶治疗轻中度痤疮的临床疗效.方法 选择2018年9月—2020年2月在郑州市第七人民医院治疗的轻中度痤疮患者127例,随机分为对照组(63例)和治疗组(64例).对照组外涂异维A酸红霉素凝胶,1～2次/d.治疗组在对照组基础上口服黄柏胶囊,3粒/次,3次/d.两组患者治疗1个月.观...     

进口10%过氧化苯甲酰乳膏(欧可喜)与国产5%过氧化苯甲酰凝胶治疗寻常痤疮临床疗效比较

研究进口10%过氧化苯甲酰乳膏治疗寻常痤疮的疗效和安全性,以国产5%过氧化苯甲酰凝胶作阳性对照,进行了随机对照平行试验.两药分别外用患处,每日2次,连续6周.结果:10%过氧化苯甲酰与5%过氧化苯甲酰比较治疗寻常痤疮的治愈率和有效率分别为30.2%,85.7%和14%,62.8% (P〈0.05).两药的药物不良反应发生率分别为17.2%和33.0%( P>0.05).结果提示进口10%过氧化苯甲酰治疗寻常痤疮、的疗效和安全性优于国产5%过氧化苯甲酰,也是一种安全有效治疗痤疮的外用药.     

Efficacy of betamethasone valerate 0.1% thermophobic foam in seborrhoeic dermatitisof the scalp: an open-label,multicentre, prospective trial on180 patients

SUMMARY

Background: Seborrhoeic dermatitis (SD) is a common chronic inflammatory disease of the skin. Topical steroid creams and/or antifungal agents are commonly used in SD, but no resolutive therapies have been available up to now. Furthermore, little data have been available regarding clinical outcomes after cessation of topical treatments. A new formulation of betamethasone valerate 0.1% in a thermophobic, low-residue, foam vehicle (Bettamousse ^*) (BVM) has become available for the topical treatment of scalp dermatoses. No data have been published hitherto regarding efficacy, safety and patient acceptability of this new formulation for the treatment of SD of the scalp.

Study aim: To assess in an open-label, prospective, multicentre trial, the efficacy, safety and patient acceptability of BVM, as compared to baseline, in SD subjects with scalp involvement.

Patients and methods: A total of 180 patients with moderate-to-severe SD of the scalp were enrolled in the trial. Efficacy was evaluated by analysing SD lesions for erythema, scaling and itching using a five-point grading score (0?=?lesion completely cured; 1?=?mild; 2?=?moderate; 3?=?severe and 4?=?very severe lesion). The clinical global (sum) score was obtained adding the score of each item. Efficacy and safety were assessed at baseline, after 4 weeks of active treatment, followed by an 8-week follow-up period with no treatment.

Results: In comparison with baseline, BVM significantly improved SD lesions. The sum score was reduced from 6.3?±?1.8 to 1.4?±?1.4 at the end of the active treatment period, (p?<?0.0001) and to 1.7?±?1.8 at the end of the 8-week follow-up period (p?<?0.0001). After active treatment, 93% of the patients had a sum score of <3). At the end of 8-week of follow-up, 88% of patients maintained a sum score <3. In addition, 85% of patients considered BVM foam to be a better topical formulation both in terms of efficacy and acceptability compared with previous treatments used.

Conclusion: BVM is an effective and well-tolerated topical treatment of scalp SD. Its clinical effect is also maintained after a 2-month wash-out period.     

Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris

Background: Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to antibiotics in the treatment of acne vulgaris. Objective: This review describes and evaluates recent clinical literature regarding the efficacy and tolerability of BPO. Methods: A PubMed literature search was conducted using the keywords benzoyl peroxide, acne, and combination therapy. Results: BPO is equally effective at concentrations of 2.5, 5.0 and 10%. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.     

Comparative study of 5% and 2.5% potassium hydroxide solution for molluscum contagiosum in children

Background: Molluscum contagiosum (MC) is a pediatric viral infection that is fairly contagious. Although various treatment methods are available, the presence of facial lesions limits options of therapy.

Aim: We aimed to test an alternative treatment consisting of application of two different concentrations of potassium hydroxide (of KOH 5% solution and of KOH 2.5% solution) aqueous solution.

Methods: In this study we evaluated the effectiveness and side-effects of daily applications of potassium hydroxide (KOH) aqueous solution at 2.5% and 5% concentrations, twice daily in 29 children with MC. Out of a total of 29 patients with molluscum contagiosum included in the study, 13 patients in the 2.5% KOH group and 12 patients in the KOH 5% group completed the study. Families were instructed to apply potassium hydroxide twice a day. The assessment of response and side-effects were performed on days 0, 15, 30, 45 and 60 (visits were numbered 1, 2, 3, 4 and 5, respectively) and one month after.

Results: We had a total of 11 (44%) patients who completely recovered after the fifth visit. While eight (66.7%) of these 11 patients were in the 5% treatment group, three (23.1%) patients were in the 2.5% treatment group, and there was a statistically meaningful difference (p?p?p?p?=?0.682).

Conclusions: Potassium hydroxide solution at a concentration of 5% was more effective than 2.5% in our patients. The treatment was well-tolerated on the face with the advantage of administration of lower concentrations. This study suggests potassium hydroxide may be a more preferable mode of treatment for molluscum contagiosum lesions on the face.     

Evaluation of serum vitamins A and E and zinc levels according to the severity of acne vulgaris

Background: Although hyperseborrhea, follicular hyperkeratinization, Propionibacterium acnes colonization and inflammation are found to be responsible in the pathogenesis of acne, the exact mechanisms are unknown. Vitamin A and E are basic antioxidants vital for health. Zinc is also an essential element for human. But these parameters of the effects on skin are not fully understood. We aimed to evaluate plasma levels of vitamin A, E and zinc in acne patients in relation to the severity of the disease.

Material and method: There were 94 acne patients who were referred to our clinic, all new diagnosed, and 56 age and sex matched healthy volunteers as control group. All patients are assessed according to Global Acne Grading System and grouped as mild, moderate, severe and very severe. Acne patients further grouped as group 1 consist of patients with mild to moderate disease; and group 2 consist of patients with severe to very severe acne. The patients with the controls and group 1 with group 2 was compared.

Results: The level of vitamin E, vitamin A and zinc were significantly lower than the control group (Table 1,p?Conclusion: Our study marks the importance of diet in patients with acne. We offer supportive dietary measures with foods rich in vitamin A and E and zinc in the acne prophylaxis and treatment. Supportive treatment with these vitamins and zinc in severe acne may lead to satisfactory results.     

An open assessment of 0.1% dithranol in a 17% urea base (‘Psoradrate' 0.1%) in the treatment of psoriasis of children

Summary

An open study was carried out in 41 children with mild to moderate psoriasis to assess the effectiveness and tolerance of treatment with a 0.1% dithranol plus 17% urea preparation applied twice daily. Thirty-four patients completed 6-weeks' treatment and 8 of them continued for a further 4 to 6 weeks. The results showed considerable improvement in lesions and, in general, the preparation was well-tolerated and considered to be highly or very acceptable by the majority of the patients. Only 3 patients had to be withdrawn for treatment-related reasons which involved soreness or burning of the skin due to the dithranol.     

Acid-Responsive Polymeric Nanocarriers for Topical Adapalene Delivery

Purpose

The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery.

Methods

The anti-acne agent, adapalene, was encapsulated in acid-responsive polymer (Eudragit® EPO) nanocarriers via nanoprecipitation. The nanocarriers were characterized in terms of particle size, surface morphology, drug-carrier interaction, drug release and permeation.

Results

Adapalene experienced a rapid release at pH 4.0 in contrast to that at pH 5.0 and 6.0. The permeation study using silicone membrane revealed a significant higher drug flux from the nanocarrier (6.5?±?0.6 μg.cm^?2.h^?1) in comparison to that (3.9?±?0.4 μg.cm^?2.h^?1) in the control vehicle (Transcutol®). The in vitro pig skin tape stripping study showed that at 24 h post dose-application the nanocarrier delivered the same amount of drug to the stratum corneum as the positive control vehicle did.

Conclusions

The acid-responsive nanocarriers hold promise for efficient adapalene delivery and thus improved acne therapy. Figure

pH liable nanocarriers enhance the adapalene delivery to acne skin.     

Variation in skin biology to climate in Shanghai,China

Purpose: To explore the relationship between climate and skin condition, and to investigate the variation of skin biology to climatic change.

Methods: In total, 2005 healthy Chinese volunteers living in Shanghai (aged 13–69 years) were recruited. Transepidermal water loss (TEWL) and SCH were tested on six sites (forehead, cheek, nasolabial, inner forearm, dorsal hand, and palm) by noninvasive devices between January 2005 and December 2012. The corresponding climate data were recorded by local Weather Bureau.

Results: TEWL was increased with atmospheric pressure and decreased with temperature, steam pressure, and relative humidity (p?p?Conclusion: Skin biological parameters are associated with climatic factors. Different sites have different sensitivity to climate factors.     

Randomized clinical trial of two anesthetic techniques for intravitreal injections: 4% liquid lidocaine on cotton swabs versus 3.5% lidocaine gel

Objective: To compare same-day and next-day pain control and safety of two anesthetic techniques utilizing 4% liquid lidocaine applied with sterile cotton swabs versus 3.5% lidocaine gel for intravitreal injections. Main outcome measures were: discomfort during anesthetic preparation and needle penetration, 1 and 24 h after injection.

Methods: Patients were randomized to alternate anesthetic method at two consecutive injections in one eye or in different eyes on the same day if requiring bilateral injections. Overall satisfaction, corneal staining, and subconjunctival hemorrhage (SCH) were compared.

Results: Fifty patients were enrolled. Both methods resulted in similar mild discomfort during anesthetic preparation, 1 and 24 h later. The gel resulted in slightly higher discomfort during needle penetration (p = 0.026). Patients were satisfied with both techniques (p = 0.91), however, 52% patients preferred gel, 33% were indifferent, and 15% preferred cotton swabs (p = 0.002). There were significantly less corneal staining (p = 0.001) and SCH (p = 0.004) after the gel.

Conclusion: Both techniques are equally effective and yield mild discomfort scores during the procedure and the next day. The gel method results in significantly less ocular surface irritation.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.