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.

A randomized controlled double-blinded split-face prospective clinical trial to assess the efficacy, safety, and tolerability of a novel 3-step routine compared to benzoyl peroxide for the treatment of mild to moderate acne vulgaris.

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.

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 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.

Dermal sensitization, safety, and tolerability of triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel from three clinical trials.

BACKGROUND: Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel. METHODS: Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne. RESULTS: A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: n = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel. CONCLUSIONS: The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.

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.

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.

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.

Novel and emerging treatment options for acne vulgaris

The principal actors in acne are the sebaceous gland, keratinocytes of the follicle and skin microbiome/innate immunity. Current acne treatments are frequently accompanied by side effects or may cause antibacterial resistance. New formulations and emerging treatments with novel mechanisms of action and improved formulations have recently been made available or are currently under development. This review provides an update on the most recent advances in topical or systemic acne therapy related to recent data on the pathophysiology of acne. A review of the most recent literature about new and emerging acne treatments since 2016 listed in the PubMed and Clinicaltrials.gov database was performed by a group of dermatologists interested in acne (GEA). Several novel treatments have been made available or are currently under development, including Clascosterone, Trifarotene and Sarecy-cline, as well as more effective and better tolerated formulations of existing compounds, such as Minocycline, Tretinoin, Tazarotene and Lidose-isotretinoin, and emerging acne therapies (including hyaluronic acid, cannabidiol, modulators of the skin microbiota, insulin-like growth factor, vaccines, bacteriophages, probiotics and antimicrobial peptides), targeting the sebaceous gland and its activity, inflammation or keratinocytes of the follicle and skin microbiome including Cutibacterium acnes. Recently, in addition to other fixed combinations, a fixed combination of adapalene and benzoyl peroxide that targets acne scars has been made available for the first time. The newly available products and other potentially emerging treatment options will increase the armamentarium of acne therapies and potentially reduce its prevalence worldwide.

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.

Efficacy of probiotic-derived lotion from Lactobacillus paracasei MSMC 39-1 in mild to moderate acne vulgaris, randomized controlled trial.

BACKGROUND: Probiotics provide benefits for reducing acne. Previous studies showed an anti-inflammatory effect of Lactobacillus paracasei. However, the clinical evidence of topical probiotic lotion and acne treatment is still lacking. OBJECTIVE: To evaluate the efficacy and safety of probiotic-derived lotion compared with 2.5% benzoyl peroxide in the treatment of mild-to-moderate acne vulgaris. METHODS: Topical probiotic-derived lotion was formulated from cell-free supernatant of L. paracasei MSMC 39-1. In vitro study showed the ability of the supernatant to inhibit both antibiotic-resistance and-susceptibility strains of C. acnes and inhibit tumor necrosis factor-α. The patients with mild-to-moderate acne vulgaris on the face were randomized to receive topical probiotic-derived lotion or 2.5% benzoyl peroxide. Acne lesion counts, erythema index, and side effects were assessed after 2 and 4 weeks of treatment. RESULTS: One hundred and four acne vulgaris patients were enrolled. After four weeks of treatment, the inflammatory acne lesion counts and erythema index significantly decreased compared with the baseline in both the probiotic-derived lotion group and 2.5% benzoyl peroxide group (p < 0.001 in both groups) without statistically significant difference between the two groups (p > 0.05). However, the comedones were not affected in both groups. Four patients (7.69%) treated with probiotic-derived lotion and 14 patients (26.92%) treated with 2.5% benzoyl peroxide reported treatment-associated side effects. CONCLUSION: Probiotic-derived lotion is safe and effective for treating mild to moderate acne vulgaris, a comparable outcome with 2.5% benzoyl peroxide. It could be an alternative treatment of acne with more minor side effects.

Topical dapsone in the treatment of acne: a systematic review.

BACKGROUND: Acne is one of the most common dermatological disorders. Initial therapies for acne include topical retinoids, benzoyl peroxide, and topical clindamycin. However, patients who fail initial therapies may benefit from alternative topicals, including dapsone gel. OBJECTIVE: To analyze the current literature studying the efficacy of topical dapsone in the treatment of acne. METHODS: PubMed, Embase, and Cochrane Library were systematically searched for clinical trials examining the efficacy of topical dapsone in the treatment of acne. RESULTS: Fourteen studies were included in the analysis. Dapsone monotherapy showed a treatment success rate of 40.1-69.4% for dapsone gel 5% and 29.8-47.0% for dapsone gel 7.5% when used for 12-16 weeks. In all studies, inflammatory lesions decreased by a larger percentage than noninflammatory or total lesions. Dapsone gel was also studied in combination with various other acne treatments, including doxycycline, oral isotretinoin, benzoyl peroxide, and topical retinoids. While mild treatment-related adverse effects, most commonly consisting of skin irritation, occurred in 2.0-75.0% of participants, no major treatment-related adverse effects were reported. LIMITATIONS: Limitations of the study include variable treatment regimens making it difficult to compare results across studies. Additionally, adverse effects and skin irritation were reported differently, and potential selection biases exist in the randomized trials. CONCLUSION: Dapsone gel offers a safe and promising alternative therapy for patients with difficult to treat acne or those who experience adverse effects to first-line therapies.

Clinical study to assess efficacy and safety of Purifying Neem Face Wash in prevention and reduction of acne in healthy adults.

BACKGROUND: Acne vulgaris is a chronic, inflammatory skin condition of pilosebaceous units. The standard treatment involves topical and oral antibiotics, retinoids, benzoyl peroxide, and other synthetic compounds, mostly associated with adverse effects. Hence, herbal skincare products are considered nowadays. AIM: To evaluate the safety and efficacy of Purifying Neem Face Wash (PNFW), an herbal skincare product in the prevention and/or reduction of mild-to-moderate acne. METHODS: An open-label, single-center, single-arm, four-week clinical study was conducted with subjects having either mild-to-moderate acne or oily skin and non-existent acne. The performance of PNFW in the reduction and/or prevention of acne was detected by counting cutaneous inflammatory and non-inflammatory acne lesions in each of the four visits. Sebum level and skin hydration of both cheeks were measured via sebumeter and corneometer, respectively. Self-assessment questionnaires were used to assess the subjects' responses toward PNFW. RESULTS: Out of 120 study subjects, 79% and 72% showed either reduction or no new appearance of inflammatory and non-inflammatory acne lesions, respectively, from baseline to Visits 3 and 4. Skin sebum level and skin hydration showed a statistically significant decrease (p < 0.001) and increase (p < 0.001), respectively, in Visits 3 and 4. Self-assessment surveys showed the satisfaction of the subjects about the product in terms of condition improvement, ease in use, and fragrance. CONCLUSION: The present study indicated the beneficial effect of the herbal ingredients (neem and turmeric) of Himalaya's PNFW in the prevention and reduction of mild-to-moderate acne with no side effects.

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.

Randomized, controlled trial testing the effectiveness and safety of 2.5% and 5% benzoyl peroxide for the treatment of pitted keratolysis.

BACKGROUND: The appropriate dosage and duration of topical benzoyl peroxide gel (BP) treatment of pitted keratolysis (PK) is controversial. OBJECTIVE: To compare the effectiveness and safety of topical 2.5% and 5% BP for the treatment of PK. MATERIALS AND METHODS: This randomized, controlled trial was conducted at Chumpol Naval Rating School, Chonburi, Thailand. Naval rating cadets with PK were randomly assigned to either a 2.5% or a 5% BP group and were requested to apply the related medication on each sole once daily, for 2 weeks. RESULTS: All 42 and 47 participants who were treated with 2.5% and 5% BP, respectively, were included in the later analysis. Self-evaluation of the foot odor level using a visual analog scale (VAS) showed significant decreases for both groups (p<.001). The pitted lesions were evaluated by dermatologists and found to have improved in the 2.5% and 5% BP groups (69.0% versus 63.8%, respectively; p=.457). Side effects did not statistically differ between the two groups (p>.05). CONCLUSIONS: Either 2.5% or 5% BP can be used for the treatment of PK and foot malodor. Due to the similarities in their efficacies and side effects, the use of 2.5% BP may be preferable.