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

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

Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study

In the treatment of mild to moderate acne vulgaris, the combination of an antibiotic and benzoyl peroxide provides enhanced efficacy over the individual agents, with the potential to decrease the emergence of resistant strains of P. acnes. To evaluate treatment regimens combining the daily use of a clindamycin/benzoyl peroxide gel, a tretinoin gel, and a clindamycin gel, the current randomized, evaluator-blind study was conducted. Results demonstrate that once-daily administration of clindamycin/benzoyl peroxide gel (combination formulation) was as effective as clindamycin/benzoyl peroxide gel + tretinoin gel + clindamycin gel. Both of these regimens provided greater efficacy than tretinoin + clindamycin. Treatment with clindamycin/benzoyl peroxide demonstrated a significant benefit over other treatments at Week 2, highlighting its rapid onset of action. All regimens were safe and generally well tolerated, with less severe peeling seen in patients who received clindamycin/benzoyl peroxide. In conclusion, the regimens that included clindamycin/benzoyl peroxide were more effective than tretinoin + clindamycin in the treatment of acne vulgaris, with no clinical advantage of adding tretinoin + clindamycin to once-daily clindamycin/benzoyl peroxide treatment.     

A multicenter efficacy and tolerability evaluation of benzoyl peroxide in a 10% urea vehicle for the treatment of acne vulgaris

BACKGROUND: Acne vulgaris is a common skin disease that affects 70 to 96% of individuals. Topical benzoyl peroxide has been used successfully for acne treatment; however, it may be accompanied by drying and or flaking skin. The addition of a 10% urea to the product excipient is theorized to moisturize the skin due to its humectant properties, aid in the efficacy of benzoyl peroxide due to its keratolytic properties, and effectively combat Propionibacterium acnes due to its antibacterial properties. OBJECTIVE: To assess the efficacy and tolerability of the treatment of acne vulgaris with multiple strengths of benzoyl peroxide in a 10% urea vehicle gel or cream and cleanser. Methods: A multicenter, non-randomized, open-label study in which 1,089 patients with acne vulgaris were enrolled at 133 participating physician office sites. Qualifying and consenting patients were prescribed either 4.5% or 8.5% benzoyl peroxide in a 10% urea vehicle cream or gel and cleanser. Additional medications were permitted during the study with the exception of those containing benzoyl peroxide. The physician assessed lesion counts, both inflammatory and non-inflammatory, at baseline and Week 4. Dryness and erythema were rated by the physician on a scale from 0 (none) to 8 (severe or deep) at baseline and Week 4. RESULTS: Nine hundred sixty-three patients completed the study. The following significant treatment arms were analyzed: patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle product only, patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products along with oral doxycycline, and patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products along with oral minocycline. A 44% (n=567) mean reduction in total lesion count was observed after 4 weeks of treatment with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products only. Dual therapy using oral doxycycline (n=17) proved to be even more effective with a significant mean reduction in lesion count of 52% after only 4 weeks of treatment. Dual therapy using oral minocycline (n=21) yielded a significant mean reduction in lesion count of 34% after 14 weeks of treatment. The overall tolerability of the treatment illustrated the utility of urea as a moisturizing agent. CONCLUSION: Benzoyl peroxide in a 10% urea vehicle gel or cream and cleanser, used once daily for 4 weeks was found to be both effective and well tolerated for the treatment of symptoms related to acne vulgaris.     

Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study

A multicenter, double-blind, randomized, parallel-group trial compared tazarotene 0.1% cream with adapalene 0.1% cream, once daily for 12 weeks, in 173 patients with facial acne vulgaris. Tazarotene was associated with a significantly greater incidence of patients achieving 50% or greater global improvement (77% vs. 55%, P < or = .01), and a significantly greater reduction in comedo count (median of 68% vs. 36%, P < or =.001, compared with adapalene. A significant between-group difference in baseline inflammatory lesion count precluded a comparison of efficacy against inflammatory acne. The most common adverse events were dryness, peeling/flaking, itching, redness/erythema, burning, and facial irritation with comparable incidences of each between groups. Mean peeling and burning levels were milder with adapalene, though were trace or less in both groups throughout. There were no significant between-group differences in the incidence of patients discontinuing due to lack of efficacy or adverse events. Tazarotene cream offers significantly greater efficacy and comparable tolerability to adapalene cream.     

Evidence-based review: fixed-combination therapy and topical retinoids in the treatment of acne

Topical fixed-combination products and topical retinoid monotherapy are established first-line treatments for mild-to-moderate acne vulgaris, yet adequate comparative data are lacking. The following evidence-based review addresses the question: "In patients with mild-to-moderate acne, are topical fixed-combination products or topical retinoids a more efficacious choice in reducing noninflammatory, inflammatory and total lesions after 12 weeks of treatment?" To identify relevant studies, a PubMed search was performed using "acne" and search terms for adapalene, tretinoin, tazarotene, benzoyl peroxide, clindamycin, or erythromycin. Forty-two studies from January 1991 to November 2009 were included. The studies were evaluated using the Strength of Recommendation Taxonomy, and all but seven received the highest level of evidence grade. To evaluate efficacy, a side-by-side comparison was made using reduction in acne lesion counts at week 12 for study groups treated with fixed-combination therapy or retinoid monotherapy. Twenty-nine studies containing relevant efficacy data for fixed-combination therapy and retinoid monotherapy are summarized here. Nine studies compared fixed-combination therapy with retinoid monotherapy; in eight of these studies, fixed-combination therapy was significantly more efficacious in reducing acne lesion counts. This evidence-based review analyzes clinical evidence to date for these therapies to provide guidance in determining appropriate treatment for patients with mild-to-moderate acne.     

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.     

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

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

The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid

A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.     

Adapalene: a review of its use in the treatment of acne vulgaris

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.     

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US, but also has approval for the treatment of acne vulgaris in many European countries where it has demonstrated success. Two randomized, multicenter, controlled clinical trials compared the effects of AzA 15% gel with those of topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily dosing regimen. The primary endpoint in the intent-to-treat analysis was a reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to 71% median reduction of facial papules and pustules compared with a 77% reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel was well-tolerated. In addition, a 1-year European observational study conducted by dermatologists in private practice evaluated the safety and efficacy of AzA 15% gel used as monotherapy or in combination with other agents in more than 1200 patients with acne. Most physicians (81.9%) described an improvement in patients' symptoms after an average of 34.6 days, and 93.9% of physicians reported patient improvement after an average of 73.1 days. Both physicians and patients assessed AzA 15% gel to be effective with 74% of patients being "very satisfied" at the end of therapy. AzA 15% gel was considered "well-tolerated" or "very well-tolerated" by 95.7% of patients. The majority of patients were more satisfied with AzA than with previous therapies. AzA 15% gel represents a new therapeutic option for the treatment of acne vulgaris.     

A new treatment for acne vulgaris combining benzoyl peroxide with clindamycin

Topical acne therapies are widely used for the treatment of mild to moderately severe acne vulgaris. However, many available treatments have limitations associated with their use, including lengthy time to response, cosmetic acceptability, and photosensitivity. Combinations of topical antibiotics and comedolytics are especially useful, but some formulations have stability challenges. A new combination formulation that contains 1% clindamycin and 5% benzoyl peroxide (BenzaClin Topical Gel) is currently available. In clinical trials, clinical improvement occurred at the first two follow-up visits and continued throughout treatment. In addition, combination therapy with clindamycin/benzoyl peroxide gel rapidly reduces Propionibacteria acnes counts and suppresses the emergence of clindamycin-resistant P. acnes. This formulation is stable at room temperature for up to 2 months after compounding. The aqueous gel vehicle is less drying, and there is no photosensitivity associated with its use. This study compares the combination treatment of 1% clindamycin and 5% benzoyl peroxide topical gel with other therapeutic options for mild to moderately severe acne vulgaris.     

Facial tolerability of topical retinoid therapy

The facial tolerability of various topical retinoids was evaluated in 253 healthy volunteers in a series of split-face, randomized, investigator-masked studies-all conducted at the same site by the same investigator. Four variables were evaluated to determine if they influenced tolerability-retinoid concentration, formulation vehicle, skin sensitivity, and individual retinoid. Lower retinoid concentrations were associated with less irritation. Vehicle influenced tolerability but whether a gel or cream formulation was better tolerated varied from retinoid to retinoid. Tolerability was superior on normal skin than "sensitive skin." On normal skin, tazarotene cream was better tolerated than tretinoin cream whereas adapalene and tretinoin microsponge gels were better tolerated than tazarotene gel. On sensitive skin, tazarotene and adapalene creams were better tolerated than tretinoin cream whereas adapalene gel was better tolerated than tazarotene gel. Retinoid concentration, vehicle, skin sensitivity, and retinoid can all affect facial tolerability. Skin vulnerability may be the most important factor.     

Topical antibacterial therapy for acne vulgaris

Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial treatments indicated for mild-to-moderate acne vulgaris. Topical antibiotics act both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous follicle and as anti-inflammatory agents. Benzoyl peroxide is a powerful antimicrobial agent that rapidly destroys both bacterial organisms and yeasts. Topical clindamycin and erythromycin have been proven to be effective against inflammatory acne vulgaris in concentrations of 1-4% with or without the addition of zinc. However, none of the antibacterials tested was more effective than benzoyl peroxide, which also has the advantage of not being associated with antimicrobial resistance.Topical antibacterial therapy should be discontinued once improvement is observed. If no improvement is observed within 6-8 weeks, the agent should be discontinued and a therapeutic switch considered. The primary limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous irritation or dryness.Antibacterial therapy can be used in combination with other agents. Combining topical antibiotics and topical retinoids may enhance the efficacy, since the retinoid will improve the penetration of the antibiotic. Combining a topical antibiotic with benzoyl peroxide may increase the bactericidal effect of the antibiotic and reduce the potential for bacterial resistance. Topical and oral antibacterials should not be used in combination for the treatment of acne vulgaris, since this association may increase the risk of bacterial resistance.     

Benzoyl peroxide in the treatment of acne vulgaris: a double-blind, multi-centre comparative study of 'Quinoderm' cream and 'Quinoderm' cream with hydrocortisone versus their base vehicle alone and a benzoyl peroxide only gel preparation

A double-blind, multi-centre general practice study was carried out to compare the effectiveness of benzoyl peroxide/potassium hydroxyquinoline sulphate cream, with or without hydrocortisone, its aqueous astringent cream base alone, and a benzoyl peroxide alcoholic gel in the treatment of 107 patients with acne vulgaris. Patients on entry were allocated at random to one of four treatment groups and instructed to apply the medication twice daily to all affected areas for 12 weeks. Assessments of the severity of acne on the face, chest and back, and response to treatment were made at 2, 4, 8 and 12 weeks. Acceptability of the treatment, i.e. 'greasiness', was also assessed by patients. The results showed that the combination cream preparation produced a greater reduction in acne scores than did the base or benzoyl peroxide alone. The addition of 1% hydrocortisone eliminated the flare reaction to benzoyl peroxide seen in patients in the other two active treatment groups. The majority of patients found the preparations cosmetically acceptable.     

Truncal acne vulgaris: the relative roles of topical and systemic antibiotic therapy

Information is limited on the management of truncal acne vulgaris. Survey results suggest that most dermatologists commonly prescribe oral antibiotic therapy when treating acne involving the chest and back. This article reports therapeutic outcomes based on an investigator-blinded, randomized, 10-week observational trial completed in patients presenting with moderate or severe truncal acne vulgaris. One group received treatment with benzoyl peroxide (BP) 9% cleanser daily, clindamycin 1% foam daily, and doxycycline 100 mg twice daily. The other group received BP cleanser 9% daily and doxycycline 100 mg twice daily without clindamycin 1% foam. Baseline, week 6, and week 10 evaluations were completed. Efficacy parameters included inflammatory and total lesion count reduction, and investigator global assessment. Global evaluations of treatment response were recorded and skin tolerability was also evaluated. This trial was designed to capture observational experience reflective of treatment of patients with truncal acne in a private practice dermatology setting.     

Tazarotene: therapeutic strategies in the treatment of psoriasis, acne and photoaging

Tazarotene is a member of the new generation of receptor-selective, synthetic retinoids for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photoaging. Though they are effective in monotherapy, clinical studies with a focus on novel combination treatments and a comparison of different agents for these skin disorders are accumulating. The concomitant use of tazarotene with a mid-potency or high-potency corticosteroid enhances the efficacy in psoriatic plaques and reduces the risk of steroid-induced skin atrophy. Combining phototherapy with adjunctive tazarotene accelerates the clinical response and reduces the cumulative UVB or PUVA exposure load. Tazarotene applied once daily is superior to adapalene monotherapy in acne vulgaris and is efficacious in the treatment of photodamage. Novel therapeutic regimens such as short-contact therapy have been developed for both acne and psoriasis in order to diminish the major adverse events like pruritus, burning, local skin irritation and erythema.     

他扎罗汀乳膏与阿达帕林凝胶随机对照治疗寻常型痤疮多中心临床试验

目的 评价国产0．1％他扎罗汀乳膏治疗面部轻中度寻常型痤疮的疗效及安全性。方法 用多中心、随机单盲对照试验方法，0．1％他扎罗汀乳膏或0．1％阿达帕林凝胶局部外用每日1次，疗程8周。在治疗前、治疗2，4和8周进行观察。入选病例142例，其中0．1％他扎罗汀乳膏组71例，完成8周观察64例。0．1％阿达帕林凝胶组71例，完成8周观察67例。结果他扎罗汀乳膏组有效率72．3％，阿达帕林凝胶组有效率62．7％。两组之间无显著统计学差异。两组的不良反应均表现为轻度到中度的局部刺激，发生率分别为28．70％和23．50％。结论 他扎罗汀乳膏治疗寻常型痤疮安全有效。     

Benzoyl peroxide microsphere cream as monotherapy and combination treatment of acne

This office-based case series describes the use of a new formulation of benzoyl peroxide (BPO) delivered via a porous microsphere cream vehicle in patients with mild to moderate acne vulgaris. While BPO has been used for many years as antimicrobial in the treatment of acne, in recent years its use has been increasingly encouraged as part of a strategy designed to reduce Propionibacterium acnes (P acnes) resistance to antibiotics. Historically, a major drawback to BPO treatment has been irritation, which may be concentration-dependent or vehicle-dependent. A new BPO microsphere cream formulation has recently been introduced and appears to offer favorable efficacy with a very low potential for irritation. This article presents a series of patients from 2 private dermatologic practices treated with a new BPO microsphere cream formulation both as monotherapy and in combination with other acne drugs.     

Safety and efficacy of micronized tretinoin gel (0.05%) in treating adolescent acne

Tretinoin is widely used in the treatment of acne. Despite significant advances in formulation development, irritation and dryness can be particularly bothersome, especially during the first 3-4 weeks, impacting adherence. Dose titration and adjunct use of moisturizers have been commonly employed. Co-prescribing with benzoyl peroxide (BPO) or a BPO/antibiotic combination is also common practice. The tretinoin molecule is unstable and can be degraded by BPO, further complicating treatment regimens. Lately, formulation technology has focused on providing more efficient penetration of the tretinoin into the skin layers so that lower concentrations of tretinoin might afford better tolerability, but maintain good efficacy; incorporating moisturizing excipients to minimize irritation; and providing greater stability to the tretinoin molecule. This approach would be particularly relevant in a pediatric acne population where efficacy/tolerability balance is important and treatment regimens must take into account lifestyles, but little data exist on the use of tretinoin in this patient population. A micronized formulation of tretinoin (0.05%) gel has been developed that provides a more efficient delivery of tretinoin, because of its optimal particle size, no degradation by BPO and better cutaneous tolerability than tretinoin microsphere (0.1%) gel without compromising efficacy in a pediatric population.