A 2.6% Benzoyl Peroxide AV Cleanser Specifically Designed for Sensitive Skin Offers Good Efficacy and Tolerability.

BACKGROUND: Mild-to-moderate acne vulgaris (AV) is common among adults, and benzoyl peroxide (BPO) has a long history of efficacy in reducing AV lesions. The efficacy of BPO is comparable for concentrations from 2.5% to 10% used as leave-on therapy, but tolerability is usually best at lower concentrations formulated in well-designed vehicles and with newer formulation methods such as micronization. This study assessed the efficacy and safety of a 2.6% BPO cleanser (Complexion Clearing AV Cleanser, CCAC) in mild-to-moderate AV. METHODS: This was a single-center, open-label, 4-week study of subjects aged 18 to 45 years (n=28) with self-perceived sensitive skin and mild-to-moderate AV. CCAC was applied twice daily (morning and evening) on damp skin. Assessments included lesion counts, clinical photography with porphyrin analysis, patient self-assessment questionnaires, collection of adverse events, and standard tolerability ratings. RESULTS: Total lesion counts were significantly reduced by week 1 of CCAC cleanser use (-25.2%, P<0.05). At week 4, AV lesions were numerically reduced but did not reach statistical significance. Additionally, there was a significant reduction of porphyrin counts at week 1 (-19.4% right side face, -28.8% left side, P<0.05 vs baseline). CCAC was well tolerated, with no significant increase in tolerability ratings at any time point compared to baseline, and patients reported good satisfaction. CONCLUSIONS: CCAC was efficacious in reducing AV lesions in as little as one week, and a trend in reduction was shown through week 4. Additionally, this 2.6% BPO cleanser was also shown to be very well tolerated and well-liked by subjects with self-perceived sensitive skin. J Drugs Dermatol. 2024;23(9):764-768. doi:10.36849/JDD.8219.

Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Male and Female Acne: Phase 3 Analysis.

BACKGROUND: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the only fixed-dose triple-combination treatment approved for acne. This post hoc analysis assessed the impact of sex on efficacy and safety/tolerability of CAB. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants aged ≥9 years with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed by sex. Assessments included treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 [clear] or 1 [almost clear]), inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates were significantly greater with CAB versus vehicle irrespective of sex (females: 53.7% vs 23.0%; males: 43.1% vs 24.6%; P<0.05, both). CAB-treated female and male participants both experienced greater reductions from baseline versus vehicle in inflammatory (females: 77.7% vs 57.9%; males: 77.5% vs 57.1%; P<0.001, both) and noninflammatory lesions (females: 72.5% vs 45.6%; males: 72.3% vs 49.6%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than vehicle. No significant differences in any efficacy measures between CAB-treated males and females were observed. Most TEAEs were of mild-to-moderate severity; no sex-based trends for safety/tolerability were observed. CONCLUSIONS: CAB demonstrated comparable efficacy, quality-of-life improvements, and safety in female and male participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment for acne. J Drugs Dermatol. 2024;23(10):873-881. doi:10.36849/JDD.8484.

Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne in Adult and Pediatric Participants.

BACKGROUND: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed.  Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402.     doi:10.36849/JDD.8357.

Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies.

BACKGROUND: Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical instability, and both medications are potentially irritating. Microencapsulation helps overcome these challenges. OBJECTIVE: Examine efficacy, safety, and tolerability of encapsulated BPO/encapsulated tretinoin (E-BPO/T) cream, 3%/0.1%. METHODS: Subjects ≥9 years old with moderate to severe acne were enrolled in 2 multicenter, double-blind, vehicle-controlled, parallel trials and randomized (2:1) to 12 weeks of once-daily E-BPO/T (n = 571) or vehicle cream (n = 287). RESULTS: E-BPO/T was significantly superior to vehicle in both studies, with more subjects achieving IGA success with E-BPO/T (38.5%/25.4%) versus vehicle (11.5%/14.7%; P < .001/P = .017). The change from baseline in inflammatory lesion count for E-BPO/T was -21.6 versus -14.8 for vehicle (P < .001) in study 1 and -16.2 versus -14.1 (P = .018) in study 2. The changes from baseline in noninflammatory lesions for E-BPO/T were -29.7 versus -19.8 for vehicle (P < .001) and -24.2 and -17.4 (P < .001) in studies 1 and 2, respectively. E-BPO/T was well tolerated in both studies. LIMITATIONS: Long-term data are not available. CONCLUSION: E-BPO/T provided statistically significant and clinically relevant improvements in IGA and inflammatory and noninflammatory lesion counts and was well tolerated in subjects with moderate to severe acne.

Tretinoin 0.1% and Benzoyl Peroxide 3% Cream for the Treatment of Facial Acne Vulgaris.

OBJECTIVE: To assess the efficacy, safety, and clinical application of tretinoin 0.1%-benzoyl peroxide 3% cream for the topical treatment of acne vulgaris. DATA SOURCES: A systematic review of the literature was performed using the terms Twyneo OR tretinoin and benzoyl peroxide OR S6G5T-3 in MEDLINE (PubMed) and EMBASE. ClinicalTrials.gov was searched to obtain completed clinical trial results not published elsewhere. STUDY SELECTION AND DATA EXTRACTION: All human studies published in English prior to November 2022 related to pharmacology, clinical trials, safety, and efficacy were evaluated for inclusion. DATA SYNTHESIS: In two 12-week, phase 3, randomized, vehicle-controlled clinical trials, tretinoin 0.1%-benzoyl peroxide 3% cream significantly reduced inflammatory and noninflammatory facial acne lesions and significantly improved Investigator Global Assessment (IGA) rating to clear or almost clear. The cream has a suitable safety profile, with application site pain and dryness as the most common adverse events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Tretinoin-BPO had similar IGA success compared to other topical retinoid and retinoid-BPO treatments for acne vulgaris. Compared to individual tretinoin and benzoyl peroxide therapy, the combination product streamlines application, which will improve medication adherence; however, the cost of tretinoin-BPO cream may be prohibitive. CONCLUSIONS: Tretinoin 0.1%-benzoyl peroxide 3% cream is safe and effective for the treatment of moderate-to-severe acne. Long-term trial data on efficacy and tolerability are not yet available.

Sixty Years of Benzoyl Peroxide Use in Dermatology.

BACKGROUND: Benzoyl peroxide (BPO) has been used extensively in industry and health care for more than a century and has been approved for the treatment of acne for over 60 years. Recently, BPO received a second approved indication by the US Food and Drug Administration (FDA) for the treatment of rosacea. Topical BPO use has historically been limited by tolerability, photosensitivity, oxidation, and, uncommonly, contact allergy. Research has led to enhanced efficacy and tolerability, as well as the combination of BPO with other topical medications. These advances have allowed extended use of BPO in additional dermatologic conditions that may not have been feasible in the past. Additionally, the role of BPO in preventing antibiotic resistance cannot be underestimated. Here, we discuss the historical limitations of BPO and recent advances developed to overcome these limitations. We also describe newly approved BPO medications and their role in aiding antibiotic stewardship. J Drugs Dermatol. 2023;22(1):54-59. doi:10.36849/JDD.7150.

Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study.

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.

Review of Tretinoin-Benzoyl Peroxide in The Treatment of Acne Vulgaris.

BACKGROUND: Acne vulgaris has a multifactorial pathogenesis, and combination therapy is recommended in most patients. A tretinoin 0.1%/benzoyl peroxide 3% (Tret-BPO) cream which uses a core-shell encapsulation system to enhance the stability of both active ingredients recently received approval from the Food and Drug Administration (FDA). OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of recently approved Tret-BPO. METHODS: A review of literature was conducted using the EMBASE, MEDLINE (Pubmed), and Clinicaltrials.gov databases in December 2021. Articles in English discussing the use of Tret-BPO in the treatment of acne vulgaris were included. RESULTS: In a phase 2 trial, Tret-BPO achieved Investigators Global Assessment (IGA) success more often (39.7%) than vehicle (12.3%; P<0.001). In 2 phase 3 trials, Tret-BPO had a higher success rate (Trial 1: 38.5% and Trial 2: 25.4%) when compared with vehicle (Trial 1: 11.5% and Trial 2: 14.7%; P<0.001 and P=0.017). LIMITATION: This review was limited by the lack of clinical trials assessing the efficacy and safety of Tret-BPO compared with other acne treatments. CONCLUSIONS: Tret-BPO is a safe and effective novel therapy for acne vulgaris. Poor adherence is a major hurdle in management; the combination of two separate first-line drugs may address this hurdle by decreasing the complexity of treatment regimens. J Drugs Dermatol. 2022;21(10):1098-1103. doi:10.36849/JDD.6808.

Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

A retrospective assessment and comparison of the effectiveness of benzoyl peroxide; the combination of topical niacinamide, gallic acid, and lauric acid; and the combination of benzoyl peroxide and erythromycin in acne vulgaris.

Acne vulgaris is a chronic inflammatory skin disease that mostly develops during adolescence and continues throughout adulthood. It affects the face, the main location of cosmetic appearance. Despite many developments in acne treatment, various combination therapies are needed to create the best option. Ninety patients were included in this study. We used the global acne grading system (GAGS) and the lesion counting and photographic standards that were used by Hayashi et al., to assess acne severity. The patients were randomly divided into three groups as group 1 (using only 5% BPO, twice a day), group 2 (using only the combination of 5% BPO + 3% erythromycin, twice a day), and group 3 (using only the combination of 4% niacinamide + 1% gallic acid + 1% lauric acid, twice a day). Thirty patients were included in each group. The scores were evaluated at weeks 0, 2, 4 and 8, and compared with each other. As a result of the study, all three treatment types were found to be effective. The combination of 4% niacinamide + 1% gallic acid + 1% lauric acid can be used as an alternative topical treatment for acne vulgaris to prevent resistance against topical antibiotics and the side effects of some other treatments.

A case series of cementless revision total knee arthroplasty in patients with benzoyl peroxide allergy.

PURPOSE: The contact allergens nickel, cobalt, and chromium are often discussed as possible triggers of allergic reactions to orthopedic implants. Additionally, acrylates and polymerization additives in bone cement (e.g., benzoyl peroxide (BPO)) have been implicated as triggers of eczema, wound healing disorders, and aseptic implant loosening. We report about six patients with aseptic loosening after total knee arthroplasty (TKA), who underwent revision surgery after testing positive for BPO hypersensitivity. METHODS: After clarification of possible other causes of implant failure, epicutaneous testing had been performed and the implants were replaced in a two-stage procedure with cementless, diaphyseal anchoring, hypoallergenic (TiNb-coated) revision endoprostheses. RESULTS: Epicutaneous testing revealed a BPO allergy in all six patients and an additional nickel allergy in three of the six patients. There was no histopathological or microbiological evidence for a periprosthetic infection. The clinical follow-up showed a low level of pain with good function, a stable knee joint, and proper implant position. The Knee Society Score (KSS) with its subscales Knee Score and Functional Score improved post-operatively from 43 to 70 points and from 47.5 to 68.3 points, respectively. Two implant-specific complications occurred: femoral stress shielding two years post-operatively with no further need for action and aseptic loosening of the tibial stem with the need of revision three years post-operatively. CONCLUSIONS: The regression of complaints after replacement with cementless and nickel-free revision implants suggests allergic implant intolerance. Implantation of a cementless, hypoallergenic endoprosthesis might, therefore, be a surgical treatment strategy in patients with evidence of allergies.

Erythema-directed digital photography for the enhanced evaluation of topical treatments for acne vulgaris.

BACKGROUND: Erythema-directed digital photography is a novel method for evaluating the efficacy and tolerability of topical acne treatments. Here, we describe three case reports in which erythema-directed digital photography was used to evaluate acne before and after up to 12 weeks of treatment with clindamycin 1%/tretinoin 0.025% (Clin-RA). MATERIALS AND METHODS: Erythema-directed digital photography was used to evaluate acne in three patients with mild-to-moderate facial acne, two of whom had refused to continue previous topical acne treatment (benzoyl peroxide 5% and clindamycin 1%/benzoyl peroxide 5%) due to persistent irritation. Acne lesions and erythema were evaluated using standard clinical photography and erythema-directed digital photography (VISIA-CR™ system) before and after 8-12 weeks of treatment with Clin-RA. RESULTS: Erythema-directed digital photography revealed background erythema from previous topical acne treatments that was not evident from standard clinical photographs and allowed a better visualization of both inflammatory and non-inflammatory lesions. In all patients, there was a clear improvement in background erythema and a reduction in acne lesions following treatment with Clin-RA. CONCLUSION: This study has demonstrated for the first time that erythema-directed digital photography can enhance the evaluation of the efficacy and tolerability of topical acne treatments. These cases show that Clin-RA was associated with improved efficacy and tolerability vs previous treatments with topical monotherapy (benzoyl peroxide 5%) or a topical fixed-dose combination (clindamycin 1%/benzoyl peroxide 5%).

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.

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.

A Case of a Paediatric Patient With Allergic Contact Dermatitis to Benzoyl Peroxide.

Allergic contact dermatitis to benzoyl peroxide can occur in up to 6.5% of those with a history of exposure to this potential allergen. Conversely, irritant contact dermatitis is very common with benzoyl peroxide and can be differentiated from allergic contact dermatitis based on the patient's history and clinical signs and symptoms. We present a case of a paediatric patient with patch test-confirmed severe allergic contact dermatitis to benzoyl peroxide requiring hospitalisation and systemic treatment.