Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Management of Acne Vulgaris: A Review.

IMPORTANCE: Acne vulgaris is an inflammatory disease of the pilosebaceous unit of the skin that primarily involves the face and trunk and affects approximately 9% of the population worldwide (approximately 85% of individuals aged 12-24 years, and approximately 50% of patients aged 20-29 years). Acne vulgaris can cause permanent physical scarring, negatively affect quality of life and self-image, and has been associated with increased rates of anxiety, depression, and suicidal ideation. OBSERVATIONS: Acne vulgaris is classified based on patient age, lesion morphology (comedonal, inflammatory, mixed, nodulocystic), distribution (location on face, trunk, or both), and severity (extent, presence or absence of scarring, postinflammatory erythema, or hyperpigmentation). Although most acne does not require specific medical evaluation, medical workup is sometimes warranted. Topical therapies such as retinoids (eg, tretinoin, adapalene), benzoyl peroxide, azelaic acid, and/or combinations of topical agents are first-line treatments. When prescribed as a single therapy in a randomized trial of 207 patients, treatment with tretinoin 0.025% gel reduced acne lesion counts at 12 weeks by 63% compared with baseline. Combinations of topical agents with systemic agents (oral antibiotics such as doxycycline and minocycline, hormonal therapies such as combination oral contraception [COC] or spironolactone, or isotretinoin) are recommended for more severe disease. In a meta-analysis of 32 randomized clinical trials, COC was associated with reductions in inflammatory lesions by 62%, placebo was associated with a 26% reduction, and oral antibiotics were associated with a 58% reduction at 6-month follow-up. Isotretinoin is approved by the US Food and Drug Administration for treating severe recalcitrant nodular acne but is often used to treat resistant or persistent moderate to severe acne, as well as acne that produces scarring or significant psychosocial distress. CONCLUSIONS AND RELEVANCE: Acne vulgaris affects approximately 9% of the population worldwide and approximately 85% of those aged 12 to 24 years. First-line therapies are topical retinoids, benzoyl peroxide, azelaic acid, or combinations of topicals. For more severe disease, oral antibiotics such as doxycycline or minocycline, hormonal therapies such as combination oral conceptive agents or spironolactone, or isotretinoin are most effective.

Acne in the first three decades of life: An update of a disorder with profound implications for all decades of life.

Acne vulgaris is a chronic, inflammatory, skin condition that involves the pilosebaceous follicles and is influenced by a variety of factors including genetics, androgen-stimulation of sebaceous glands with abnormal keratinization, colonization with Cutibacterium acnes (previously called Propionibacterium acnes), and pathological immune response to inflammation. Acne can occur at all ages and this discussion focuses on the first three decades of life. Conditions that are part of the differential diagnosis and/or are co-morbid with acne vulgaris are also considered. Acne in the first year of life includes neonatal acne (acne neonatorum) that presents in the first four weeks of life and infantile acne that usually presents between 3 and 6 months of the first year of life with a range of 3 to 16 months after birth. Acne rosacea is a chronic, inflammatory, skin condition that is distinct from acne vulgaris, typically presents in adults, and has four main types: erythemato-telangiectatic, papulopustular, phymatous and ocular. Treatment options for acne vulgaris include topical retinoids, topical benzoyl peroxide, antibiotics (topical, oral), oral contraceptive pills, isotretinoin, and others. Management must consider the increasing impact of antibiotic resistance in the 21st century. Psychological impact of acne can be quite severe and treatment of acne includes awareness of the potential emotional toll this disease may bring to the person with acne as well as assiduous attention to known side effects of various anti-acne medications (topical and systemic). Efforts should be directed at preventing acne-caused scars and depigmentation on the skin as well as emotional scars within the person suffering from acne.

A break-even analysis of benzoyl peroxide and hydrogen peroxide for infection prevention in shoulder arthroplasty.

BACKGROUND: Newer strategies to decolonize the shoulder of Cutibacterium acnes may hold promise in minimizing the occurrence of infections after shoulder arthroplasty, but little is known about their cost-effectiveness. Break-even models can determine the economic viability of interventions in settings with low outcome event rates that would realistically preclude a randomized clinical trial. We used such modeling to determine the economic viability of benzoyl peroxide and hydrogen peroxide for infection prevention in shoulder arthroplasty. METHODS: Skin decolonization protocol costs ($11.76 for benzoyl peroxide; $0.96 for hydrogen peroxide), baseline infection rates for shoulder arthroplasty (0.70%), and infection-related care costs ($50,230) were derived from institutional records and the literature. A break-even equation incorporating these variables was developed to determine the absolute risk reduction (ARR) in the infection rate to make prophylactic use economically justified. The number needed to treat was calculated from the ARR. RESULTS: Topical benzoyl peroxide is considered economically justified if it prevents at least 1 infection out of 4348 shoulder arthroplasties (ARR = 0.023%). Hydrogen peroxide is economically justified if it prevents at least 1 infection out of 50,000 cases (ARR = 0.002%). These protocols remained economically viable at varying unit costs, initial infection rates, and infection-related care costs. CONCLUSIONS: The use of topical benzoyl peroxide and skin preparations with hydrogen peroxide are highly economically justified practices for infection prevention in shoulder arthroplasty. Efforts to determine drawbacks of routine skin decolonization strategies are warranted as they may change the value analysis.

Cutibacterium acnes persists despite topical clindamycin and benzoyl peroxide.

BACKGROUND: Cutibacterium (formerly Propionibacterium) acnes persists in the dermis despite standard skin antiseptic agents, prompting some surgeons to use topical antimicrobials such as benzoyl peroxide and clindamycin prior to shoulder arthroplasty surgery. However, the efficacy of these topical agents has not been established. METHODS: The upper backs of 12 volunteers were randomized into 4 treatment quadrants: topical benzoyl peroxide, topical clindamycin, combination topical benzoyl peroxide and clindamycin, and a negative control. The corresponding topical agents were applied to each site twice daily for 3 days. A 3-mm dermal punch biopsy specimen was obtained from each site and cultured for 14 days to assess for C acnes growth. Positive cultures were assessed for the hemolytic phenotype. The McNemar test was used to compare the proportion of positive cultures in each group. RESULTS: C acnes grew in 4 of 12 control sites (33.3%), 1 of 12 benzoyl peroxide sites (8.3%), 2 of 12 clindamycin sites (16.7%), and 2 of 12 combination benzoyl peroxide-clindamycin sites (16.7%). The C acnes hemolytic phenotype was present in 2 of 12 control specimens (16.7%) compared with 0 (0.0%) in the benzoyl peroxide group, 2 of 12 (16.7%) in the clindamycin group, and 2 of 12 (16.7%) in the combination benzoyl peroxide-clindamycin group. There were no statistically significant differences between treatment arms. CONCLUSION: The topical application of benzoyl peroxide and clindamycin did not eradicate C acnes in all subjects. The clinical implications of these findings are yet to be determined.

Treatment of acne. / Behandling av akne.

Acne should not be perceived as a self-limiting affliction of adolescence. Due to the growing problem of antimicrobial-resistant bacteria, restrictive use of peroral and topical antibiotics is recommended. There are a number of effective agents for topical treatment of mild to moderate acne. In cases of severe, therapy-resistant acne, treatment with peroral isotretinoin is recommended.

Facial swelling in an adolescent.

Clinical findings, as well as the patient's age and sex, pointed to the diagnosis.

Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris: A randomized open-labeled study.

Insulin, insulin-like growth factor-1 (IGF-1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient-sensitive kinase. Metformin, through inhibition of mTORC1 may improve acne. A 12-week, randomized, open-labeled study evaluated the efficacy and safety of metformin as an adjunct for moderate to severe facial acne. In total, 84 patients received either oral tetracycline 250 mg bd and topical benzoyl peroxide 2.5% with or without metformin 850 mg daily. Evaluations constituted lesion counts, the Cardiff Acne Disability Index (CADI), metabolic parameters and treatment success rate (Investigators Global Assessment score of 0 or 1 or improvement of two grades). Treatment success rates were higher in the metformin group (66.7% vs. 43.2%; p = .04). The mean percentage reduction from baseline in total lesion counts at Week 12 was greater in the metformin group (71.4% vs. 65.3%; p = .278). The CADI scores showed a greater mean reduction in the metformin group (4.82 vs. 4.22; p = .451). Metformin was equally efficacious in improving acne in lean and overweight subjects. Gastrointestinal symptoms were noted in 31.7% of subjects on metformin. This study presents favorable data for metformin as an adjunct for acne treatment. Further randomized placebo-controlled studies are required.

A comparative study on the effectiveness of herbal extracts vs 2.5% benzoyl peroxide in the treatment of mild to moderate acne vulgaris.

BACKGROUND: Although there is a standard guideline for the treatment of acne, it is still a common skin disease, and suboptimal medication adherence is a major reason for treatment failure. Herbal extracts are an interesting alternative medicine because they consist of a variety of active ingredients. Moreover, herbal extracts may have improved therapeutic efficacy because of the combination of various herbs. OBJECTIVES: To evaluate the effectiveness of herbal extracts for the treatment of mild to moderate acne vulgaris. METHODS: A total of 77 patients were randomized to receive either an herbal extract or 2.5% benzoyl peroxide, which were applied for a period of 12 weeks. Acne lesion counts, adherence, porphyrin counts, the Dermatology Life Quality Index, satisfaction and side effects were assessed. RESULT: At the 12-week point, the acne lesion counts decreased, with statistically significant differences from the baseline values in both groups and for all types of acne (P-value < 0.001). The adherence rate was significantly higher in the patients using the herbal extract than in the patients using 2.5% benzoyl peroxide (P-value = 0.002). There was no statistically significant difference in terms of porphyrin counts, spot scores, the Dermatology Life Quality Index or satisfaction with efficacy between the groups; however, satisfaction with drug administration was significantly higher in the patients using the herbal extract (P-value = 0.001). CONCLUSION: Herbal extracts could be beneficial for anti-acne pharmaceutical preparations and may be used as an alternative medicine for patients with mild to moderate acne vulgaris who do not adhere to benzoyl peroxide treatment.

A Randomized Controlled Tolerability Study to Evaluate Reformulated Benzoyl Peroxide Face Washes for Acne Vulgaris

Introduction: This randomized, evaluator-blind, single-center, parallel-group study sought to evaluate the tolerability of two reformulated face washes containing benzoyl peroxide (BPO) in adults with mild to moderate acne vulgaris. Methods: Healthy adults with mild to moderate acne vulgaris were randomly allocated (1:1:1) to one of two reformulated test products (containing BPO at a concentration of either 4% or 10%) or an older formulation containing 10% BPO (reference product), which they applied twice daily for 21±2 days. The primary tolerability assessment was clinical assessment of signs and symptoms of cutaneous irritation by a dermatologist. The primary outcome was the total dermatologist assessment score (maximum total assessment score=12, indicating the most severe skin irritation). Secondary assessments were ophthalmologist assessments, subject self-assessments, and adverse events. Results: 133 adults were randomized and treated. The total dermatologist score changed by a mean of -0.08 (95% confidence interval [CI] -0.192, 0.038) from baseline to day 21 in the 4% BPO cleanser group, by 0.05 (95% CI -0.021, 0.121) in the 10% BPO cleanser group, and by -0.02 (95% CI -0.105, 0.059) in the reference product group. There was no clinically significant difference between the reference product and the 4% BPO cleanser or 10% BPO cleanser in the mean change from baseline. Mean changes from baseline in ophthalmologist assessment scores and subject self-assessment scores for the 4% and 10% BPO test products were also comparable to those of the reference product. Dermal responses were consistent with the known effects of topical BPO application and no serious safety issues were reported. Discussion: There was no difference in the local tolerance profile of the reformulated BPO-containing face washes when compared with an older formulation. Study registration: www.gsk-clinicalstudyregister.com (study 206239). J Drugs Dermatol. 2019;18(4):350-356

Topical Retinoids in Acne Vulgaris: A Systematic Review.

BACKGROUND: Topical retinoids are a first-line treatment for acne vulgaris. OBJECTIVE: This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris. METHODS: A PubMed and Embase search was conducted using the search terms 'adapalene,' 'tretinoin,' 'tazarotene,' and 'acne vulgaris.' Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria. RESULTS: Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator's Static Global Assessment (24.1-28.8% and 13.3-17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1-34.9% vs 7-11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64-78.9% vs 41-56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012). CONCLUSIONS: Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

A randomized controlled trial of topical benzoyl peroxide 2.5% gel with a low glycemic load diet versus topical benzoyl peroxide 2.5% gel with a normal diet in acne (grades 1-3).

BACKGROUND: The improvement in insulin resistance and acne lesions on low glycemic load diets in various studies suggests that diet plays a significant role in acne pathogenesis. AIMS: To compare the efficacy of a low glycemic load diet plus topical benzoyl peroxide 2.5% gel with that of only topical benzoyl peroxide 2.5% gel in grades 1, 2 and 3 of acne vulgaris. METHODS: In a randomized controlled trial, 84 patients with grades 1, 2 and 3 acne vulgaris were divided into two groups, to receive a low glycemic load diet and no dietary intervention respectively. Acne lesions (face) were scored and graded at baseline and 4, 8 and 12 weeks. Homeostasis model assessment of insulin resistance and body mass index were measured during the first and last visits. Statistical analysis was done with Statistical Package for the Social Sciences, version 17.0. RESULTS: Both groups showed significant reduction in acne counts at 12 weeks (P = 0.931) with no statistically significant difference between the groups. The differences in body mass index and homeostasis model assessment of insulin resistance between the groups were statistically significant (P = 0.0001). Group 1 showed reductions in body mass index and homeostasis model assessment of insulin resistance values at the end of the study, whereas group 2 did not. LIMITATIONS: Application of mild topical cleanser in both the groups might have contributed to the improvement in epidermal barrier function, and topical application of 2.5% of benzoyl peroxide gel in both groups contributed to the improvement in acne counts. CONCLUSIONS: A low glycemic load diet did not result in any significant improvement in acne counts.

Treatment of Moderate Acne Vulgaris in Fitzpatrick Skin Type V or VI: Efficacy and Tolerability of Fixed Combination Clindamycin Phosphate 1.2%/Benzoyl Peroxide 3.75% Gel.

BACKGROUND: Acne vulgaris (acne) is the most common skin disease in patients who have darker skin with most frequent sequelae of post inflammatory hyperpigmentation (PIH). METHODS: Open label study in 20 patients (mean age 32 years) with Fitzpatrick Skin Type V or VI and with moderate facial acne treated with clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel (CL-BP 3.75%) once-daily for 16 weeks. Assessments included improvement in Investigator Global Assessment (IGA) of acne severity, PIH severity and distribution, and lesion count reduction. Adverse events (AEs) were assessed throughout. RESULTS: Significant reductions in inflammatory, noninflammatory and total lesions occurred within the first 4 weeks compared to baseline. At week 16, percent changes from baseline were 76%, 62%, and 71%, respectively (all P less than equal to .0002). There was also a significant reduction in IGA to week 16 (P equals.0001); 70% (N=14) of patients were 'clear' or 'almost clear' and all patients experienced at least a 1-grade improvement in IGA. Additionally, PIH severity and distribution were also significantly reduced by week 16. In 40% of patients PIH severity was rated as 'none' or 'slight'; 19 (95%) and 15 (75%) of patients experienced at least a 1-grade improvement in PIH severity or distribution. Ten patients experienced a total of 21 AEs. There were no serious AEs. Only one AE was possibly related to study drug (facial tattoo tightening) and resolved with no residual effects at the end of the study. CONCLUSIONS: Patients with Fitzpatrick Skin Type V and VI treated with clindamycin phosphate 1.2%/ benzoyl peroxide 3.75% gel experienced significant reductions in facial acne severity, lesion counts and PIH severity/distribution. Tolerability was excellent. J Drugs Dermatol. 2018;17(10):1107-1112.

Codelivery of benzoyl peroxide & adapalene using modified liposomal gel for improved acne therapy.

AIM: Current study investigates therapeutic efficacy and tolerability of benzoyl peroxide (BPO)- and adapalene (AD)-loaded modified liposomal gel (BPO-AD-mLipo gel) for improved acne therapy. MATERIALS & METHOD: BPO-AD-mLipo were optimized and loaded in Carbopol gel. Both BPO-AD-mLipo and BPO-AD-mLipo-gel were extensively characterized for different quality attributes. Ex vivo dermal bioavailability, dermal distribution, in vivo anti-acne efficacy and skin irritation studies were performed and compared with marketed formulation (Epiduo®, Galderma Laboratories LP, TX, USA). RESULTS: BPO-AD-mLipo illustrated size 256.4 ± 9.3 nm with polydispersity index âˆ¼ 0.2. Significantly enhanced dermal bioavailability (AD-2.1, 5.4; BPO-3.0, 7.83-fold) and reduction in skin irritation and papule density in animal model were observed with BPO-AD-mLipo-gel as compared with free drugs and Epiduo, respectively. CONCLUSION: BPO-AD-mLipo gel provides effective and safer alternative approach for codelivery of anti-acne drugs.

Topical Vehicle Formulations in the Treatment of Acne.

Topical treatment is the mainstay of acne therapy. The most commonly prescribed topical medications for acne include benzoyl peroxide, clindamycin, and retinoids. Despite their effectiveness in treating mild to moderate acne vulgaris, these topical medications are found to be irritating, and are historically associated with poor tolerability and diminished patient adherence. Thus, choosing the right formulation that will be effective and well tolerated is essential. Novel formulations that optimize drug concentration and utilize improved delivery vehicles have helped to enhance the tolerability and efficacy, and allow for less frequent application or co-application of drugs that were previously considered incompatible. This article will review the goals of topical therapy for the treatment of acne, in addition to common therapies and their challenges. Advanced formulations and combination formulations of benzoyl peroxide, clindamycin, and tretinoin will also be discussed. J Drugs Dermatol. 2018;17(6 Suppl):s6-10.