How Much Do We Know about Maintaining Treatment Response after Successful Acne Therapy? Systematic Review on the Efficacy and Safety of Acne Maintenance Therapy.

After cessation of successful initial acne therapy, patients often experience flares. Consecutive maintenance treatment after successful induction therapy is promoted by guidelines; however, little is known about the efficacy/safety of different maintenance regimens. A systematic review on acne maintenance treatments was conducted. We identified 5 randomized controlled trials [RCTs; adapalene vs. vehicle or vs. no treatment (3 RCTs), adapalene/benzoyl peroxide (BPO) vs. vehicle, combination/monotherapy of minocycline (systemic)/tazarotene/placebo] and 3 non-RCTs on systemic isotretinoin, adapalene/BPO and azelaic acid. The results of adapalene versus vehicle/no treatment varied depending on the reported outcome. The 'number of patients maintaining at least 50% improvement' counting inflammatory lesions/non-inflammatory lesions with adapalene was superior to vehicle (risk ratio, RR 1.24, 95% confidence interval, CI 1.08-1.43/RR 1.34, 95% CI 1.18-1.59). However, no significant differences were found in 2 of 3 RCTs for maintaining 'clear/almost clear' or 'mild acne' or on the global grading score. For the combination regimens of minocycline/tazarotene/placebo, no significant differences were found. Adapalene/BPO was superior to vehicle counting inflammatory lesions/non-inflammatory lesions (RR 1.61, 95% CI 1.31-1.99; RR 1.80, 95% CI 1.44-2.26). Due to the scarcity of studies, few conclusions can be drawn. More homogeneous outcome measures and specific maintenance study designs may lead to more robust findings.

Stratum Corneum Abnormalities and Disease-Affected Skin: Strategies for Successful Outcomes in Inflammatory Acne.

Stratum corneum (SC) abnormalities are associated with disease-affected skin conditions such as inflammatory acne. Current topical acne treatment options including benzoyl peroxide and retinoids can worsen the barrier dysfunctions by increasing transepidermal water loss, depleting SC vitamin E levels, and relatively decreasing SC thickness. However, strategies exist to employ these treatments in a more effective manner and lessen barrier function disruption including use of less irritating vehicles or concomitant application of moisturizers. Patients also play a role in the outcome of their skin barrier function based on their compliance and administration technique. By increasing patient compliance and proper application of treatments, patient skin barrier function can improve. Additionally, future treatments are on the horizon that may customize acne therapy at a molecular level.

J Drugs Dermatol. 2016;15(10):1170-1173.

Topical and oral antibiotics for acne vulgaris.

Antibiotics, both oral and topical, have been an integral component of the management of acne vulgaris (AV) for approximately 6 decades. Originally thought to be effective for AV due to their ability to inhibit proliferation of Propionibacterium acnes, it is now believed that at least some antibiotics also exert anti-inflammatory effects that provide additional therapeutic benefit. To add, an increase in strains of P acnes and other exposed bacteria that are less sensitive to antibiotics used to treat AV have emerged, with resistance directly correlated geographically with the magnitude of antibiotic use. Although antibiotics still remain part of the therapeutic armamentarium for AV treatment, current recommendations support the following when used to treat AV: 1) monotherapy use should be avoided; 2) use benzoyl peroxide concomitantly to reduce emergence of resistant P acnes strains; 3) oral antibiotics should be used in combination with a topical regimen for moderate-to-severe inflammatory AV; and 4) use oral antibiotics over a limited duration to achieve control of inflammatory AV with an exit plan in place to discontinue their use as soon as possible. When selecting an oral antibiotic to treat AV, potential adverse effects are important to consider.

Gender as a clinically relevant outcome variable in acne: benefits of a fixed combination clindamycin phosphate (1.2%) and benzoyl peroxide (2.5%) aqueous gel.

OBJECTIVE: There is an increasing interest in gender differences both in the pathogenesis and treatment of skin diseases. We investigate whether there were any treatment differences in male and female subjects treated with clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 2.5% gel as monotherapy for moderate to severe acne. METHODS: We performed a post hoc analysis of the efficacy and cutaneous tolerability in 797 subjects receiving clindamycin phosphate 1.2%/BPO 2.5% gel from two 12-week, multicenter studies that enrolled 2,813 subjects with moderate to severe acne. Efficacy and tolerability were compared with both male and female subjects, overall and stratified by age (12-18 years and #18 years). RESULTS: Absolute mean reductions in lesion counts with clindamycin phosphate 1.2%/BPO 2.5% gel were comparable and not significantly different across gender and age groups. Net reductions were greater in the adolescent groups. Treatment success in the older males was significantly greater (P=.046) compared with the adolescent males, and the difference between the male and female adolescent groups was significant in favor of the female subjects (P=.046). Cutaneous tolerability was comparable across all groups and between clindamycin phosphate 1.2%/BPO 2.5% gel and vehicle. CONCLUSIONS: Clindamycin phosphate 1.2%/BPO 2.5% gel provided comparable reductions in lesion counts across all 4 groups; however, the impact was greater in those subjects with more severe acne (the older males and adolescent females), and net benefit was greater in the adolescent subjects.

Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris.

Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.

Advances in topical delivery systems in acne: new solutions to address concentration dependent irritation and dryness.

Formulation development is key to the successful treatment of acne. There has been significant progress over the past few years, but not all developments can be universally applied. An effective topical formulation must provide chemical stability and enhanced penetration of active ingredients at optimal concentrations for efficacy and safety; be cosmetically acceptable; and not add side effects of its own. Both retinoids and fixed combinations containing benzoyl peroxide are commonly used to treat acne, but both have the potential to cause troublesome dose-dependent irritation and dryness. Excipients such as surfactants and alcohol have added to the problem. Two products have recently been introduced where a combination of micronization skills and well-chosen excipients has minimized irritation and dryness without compromising efficacy. Results from two major studies are discussed in this article.

Community study of fixed-combination adapalene 0.1% and benzoyl peroxide 2.5% in acne.

A new fixed-dose combination formulation of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has shown excellent efficacy and safety in registration studies; however, it can be difficult to judge the real-world performance of a product using only the results from controlled clinical trials. This 12-week, open-label, community-based study evaluated adapalene/BPO in 91 patients with mild to moderate acne (20-50 inflammatory lesions and 30-100 noninflammatory lesions) who were treated at dermatology centers throughout Argentina. The study evaluated efficacy, described the most common side effects, determined tolerability, and assessed the level of patient satisfaction with treatment. By week 12, there were statistically significant reductions in both inflammatory and noninflammatory lesions (80.6% and 69.3% from baseline, respectively; P < .001); there were also significant improvements in the Investigator's Global Assessment scores (median score, 2.9 at baseline and 1.0 at week 12; P < .001). By week 12, 67% of patients were rated clear or almost clear by investigators. Local tolerability was good overall. When cutaneous irritation was present, it typically occurred in the first 2 weeks of treatment and improved or resolved with continuing therapy. Patients were highly satisfied with the results of treatment, and 74% of patients felt that they had marked or total improvement by week 12. Patient survey also revealed that 94% rated the efficacy as good or very good and 87.5% rated tolerability as good or very good. A significant majority (81%) felt that the treatment met expectations, and 62% perceived that improvement had been rapid during adapalene/BPO therapy. These results demonstrate that adapalene/BPO has good efficacy and tolerability in routine practice, resulting in continuous reductions in lesion counts throughout the study. Adapalene/BPO therapy is also associated with high patient satisfaction, which is important for therapeutic adherence and satisfaction with the physician's care.

Case-based experience with the simultaneous use of a fixed topical antibiotic/benzoyl peroxide combination and a topical retinoid in the optimization of acne management.

Treatment options for acne vulgaris have expanded considerably in the past decade. The main goals of treatment continue to be reducing acne lesions while maintaining patient satisfaction and adherence to treatment. As dermatologists, the art of treatment is to develop, fine-tune, and utilize combinations of agents to increase compliance, thereby optimizing patient outcomes. In acne management, one strategy involves concomitant use of topical retinoids with benzoyl peroxide or a fixed combination of topical antibiotic/benzoyl peroxide. This strategy requires application of one product in the morning and one in the evening due to concerns of benzoyl peroxide-induced degradation of retinoid activity. Presented are two cases in which a topical retinoid and a topical fixed combination of clindamycin/benzoyl peroxide were used concomitantly in patients with mild-to-moderate acne. Research-based and practical rationale on the simultaneous use of newer-generation retinoids and benzoyl peroxide-based products, without concern of retinoid degradation, is discussed.

Improving treatment outcomes: tolerability of a fixed-combination clindamycin 1%-benzoyl peroxide 5% hydrating gel as monotherapy or in combination with a retinoid.

Patient adherence to acne therapy is a fundamental element of successful treatment outcomes, which can be increased by the selection of rapidly acting, well-tolerated medications used in simplified regimens. A fixed-combination monotherapy gel containing clindamycin 1% and benzoyl peroxide 5% (C/BPO) has an established safety and efficacy profile through almost a decade of published literature and clinician experience. This unique product may improve a patient's adherence to therapy by providing a well-tolerated and efficacious once-daily monotherapy with multiple mechanisms of action. This article reviews data outlining the enhanced tolerability of the fixed-combination C/BPO gel both alone and when used with a retinoid. The favorable tolerability profile of C/BPO hydrating gel may impart additional benefit to the patient in helping to maintain adherence to treatment.

A 3-step acne system containing solubilized benzoyl peroxide versus clindamycin-benzoyl peroxide.

A 3-step acne system has been developed to enhance the bioavailability and follicular penetration of benzoyl peroxide (BPO). Participants with mild to moderate facial acne vulgaris were randomly assigned to 10 weeks' facial treatment with the 3-step acne system (proprietary salicylic acid cleanser 2% twice daily, proprietary salicylic acid toner 2% once daily, and solubilized BPO gel 5% twice daily) or with control cleanser twice daily plus clindamycin 1%-BPO 5% gel (jar formulation) twice daily. Among 139 participants enrolled, the 3-step acne system was at least as effective as clindamycin-BPO in reducing noninflammatory lesion counts in the early weeks of treatment in the absence of an antibiotic (mean reductions were 27% vs 13%, 39% vs 25%, 40% vs 33%, and 42% vs 42% at weeks 2, 4, 6, and 10, respectively) (all not significant). Both regimens were associated with comparable reductions in inflammatory lesion counts at all time points. Both regimens also were generally well-tolerated with mean scores for erythema, dryness, peeling, burning/stinging, and itching less than mild in both groups at all time points. The 3-step acne system is at least as effective as clindamycin-BPO in reducing noninflammatory lesion counts in the early weeks of treatment in the absence of an antibiotic, which is likely attributed to the solubilized BPO formulation.

Facial swelling in an adolescent.

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

An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients.

OBJECTIVE: We sought to evaluate efficacy, safety, and tolerability of a combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% (clindamycin-BPO 2.5%) aqueous gel in moderate to severe acne vulgaris. METHODS: A total of 2813 patients, aged 12 years or older, were randomized to receive clindamycin-BPO 2.5%, individual active ingredients, or vehicle in two identical, double-blind, controlled 12-week, 4-arm studies evaluating safety and efficacy (inflammatory and noninflammatory lesion counts) using Evaluator Global Severity Score and subject self-assessment. RESULTS: Clindamycin-BPO 2.5% demonstrated statistical superiority to individual active ingredients and vehicle in reducing both inflammatory and noninflammatory lesions and acne severity. Visibly greater improvement was observed by patients with clindamycin-BPO 2.5% as early as week 2. No substantive differences were seen in cutaneous tolerability among treatment groups and less than 1% of patients discontinued treatment because of adverse events. LIMITATIONS: Data from controlled studies may differ from clinical practice. CONCLUSIONS: Clindamycin-BPO 2.5% provides statistically significant greater efficacy than individual active ingredients and vehicle with a highly favorable safety and tolerability profile.

Solubilized benzoyl peroxide versus benzoyl peroxide/clindamycin in the treatment of moderate acne.

BACKGROUND: Benzoyl peroxide (BPO) is poorly soluble. A solubilized formulation of BPO has been developed to maximize its bioavailability and enhance follicular penetration. METHODS: Patients with acne vulgaris were randomly assigned to receive solubilized BPO 5% gel on one side of the face and a BPO 5%/clindamycin 1% combination product on the contralateral side, twice daily for 4 weeks. RESULTS: Of 23 patients enrolled, 100% completed the study. Reductions in lesion count with the solubilized BPO gel were at least as great as with BPO/clindamycin--and significantly greater (P< or =.05) for noninflammatory lesions at week 1 and inflammatory lesions at week 4. Both regimens were generally well tolerated and patient satisfaction was comparable. CONCLUSIONS: Solubilized BPO 5% gel monotherapy offers significantly greater efficacy, and comparable patient satisfaction, compared with BPO/clindamycin. The early reduction in lesion counts observed with the solubilized BPO gel in the absence of an antibiotic is clinically relevant.

Adapalene-benzoyl peroxide once-daily, fixed-dose combination gel for the treatment of acne vulgaris: a randomized, bilateral (split-face), dose-assessment study of cutaneous tolerability in healthy participants.

Combination therapy is an effective approach to simultaneously target multiple pathogenic factors of acne. International consensus guidelines recommend the use of topical retinoids and benzoyl peroxide (BPO) for acne treatment. These drugs are often prescribed as a free combination without any safety concern associated with antibiotic use. A 3-week, randomized, controlled, investigator-blinded, single-center, bilateral (split-face), dose-assessment study was conducted comparing the cutaneous tolerability of 2 adapalene-BPO fixed-dose combination products versus various concentrations of BPO monotherapy applied once daily. Sixty healthy participants were randomized to one of the following treatment groups: adapalene 0.1%-BPO 2.5% combination product versus BPO 2.5% monotherapy; adapalene 0.1%-BPO 2.5% combination product versus BPO 5% monotherapy; adapalene 0.1%-BPO 5% combination product versus BPO 5% monotherapy; and adapalene 0.1%-BPO 5% combination product versus BPO 10% monotherapy. Assessments included total sum score (TSS) of irritation signs/ symptoms (erythema, scaling/desquamation, dryness, pruritus, stinging/burning) averaged over all postbaseline visits, individual irritation signs/symptoms (worst score), and adverse events. The overall cutaneous tolerability profile of the adapalene 0.1%-BPO 2.5% combination product was better than the combination with BPO 5% and similar to BPO 2.5% or 5% monotherapy. The combination product with BPO 5% induced significantly more irritation than BPO 5% monotherapy (P < .001) or BPO 10% monotherapy (P = .001). In conclusion, the new fixed-dose adapalene 0.1%-BPO 2.5% combination product provided the best overall cutaneous tolerability profile relative to BPO monotherapy.

Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: a randomized study.

BACKGROUND: There is no effective treatment for progressive macular hypomelanosis. Recent findings indicate that Propionibacterium acnes may play a role in the pathogenesis. OBJECTIVES: We sought to compare the effectiveness of antimicrobial therapy with anti-inflammatory therapy in patients with progressive macular hypomelanosis. METHODS: A total of 45 patients were randomized to a within-patient left-right comparison study of benzoyl peroxide 5% hydrogel/clindamycin 1% lotion in combination with UVA irradiation versus fluticasone 0.05% cream in combination with UVA irradiation. Repigmentation was determined by photometric measurements of changes in skin color and by patient and dermatologist assessment using before and after photographs. RESULTS: Benzoyl peroxide 5% hydrogel, clindamycin 1% lotion, and UVA led to better repigmentation than fluticasone 0.05% cream in combination with UVA irradiation in all measurements. (Photometric measurements P = .007, patient assessment P < .0001, and dermatologist assessment P < .0001.) LIMITATIONS: There was difficult objective color measurement. Therefore, subjective assessment has important additional value. Right-left comparisons have certain inherent limitations. CONCLUSION: Antimicrobial therapy in conjunction with light was more effective in repigmentation in patients with progressive macular hypomelanosis than a combination of anti-inflammatory therapy and light.

Combining clindamycin 1%-benzoyl peroxide 5% gel with multiple therapeutic options.

This article reports on recent studies and case reports that evaluated the stability, tolerability, and efficacy of clindamycin 1%-benzoyl peroxide 5% tube gel in combination with topical retinoids and oral antibiotics. Overall, these combinations appeared to be well-tolerated, effective, and, as reported in the case studies, adaptable to common clinical practice.

Managing acne vulgaris effectively.

The management of acne is a gratifying experience. Available treatments are effective, relatively nontoxic and generally safe. However, there is no quick fix. Antibiotics, hormone therapies and topical therapies are maintenance treatments. Isotretinoin can induce remission, as can some of the newer physical modalities of lights, lasers and radiofrequency devices. Effective management of acne often requires using a combination of treatments that act on different parts of the pathogenic process of acne development.