A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide (Duac®) and erythromycin + zinc acetate (Zineryt®) in the treatment of mild to moderate facial acne vulgaris

BACKGROUND: Antibiotics are often combined with other agents to provide topical acne treatments that are effective against both inflammatory and non-inflammatory lesions and minimize the development of antibiotic resistance. OBJECTIVES: To compare the clinical effectiveness of two combination treatments for facial acne: a ready mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn). METHODS/PATIENTS: In this assessor-blind, randomized study, 73 patients were treated with CDP + BPO once daily and 75 patients with ERY + Zn twice daily. The treatment period was 12 weeks and lesion counts and global improvement were assessed at weeks 1, 2, 4, 8 and 12. RESULTS: CDP + BPO showed an earlier onset of action with a faster significant reduction in total lesion counts than ERY + Zn. The proportion of patients with at least a 30% improvement in non-inflammatory lesions at week 1 was 31.5% for CDP + BPO and 17.3% for ERY + Zn; the corresponding percentages for inflammatory lesions were 39.7% and 29.3%. A difference was also observed at week 2 (53.4% vs. 36.0% for non-inflammatory lesions and 72.6% vs. 53.3% for inflammatory lesions). The trend in favour of CDP + BPO, although less marked, continued to the end of the study, with reductions in the total lesion count at endpoint of 69.8% for CDP + BPO group and 64.5% for ERY + Zn group. Both treatments were well tolerated. CONCLUSIONS: CDP + BPO and ERY + Zn are effective treatments for acne but CDP + BPO has an earlier onset of action that should improve patient compliance.     

Prospective, open-label, comparative study of clindamycin 1%/benzoyl peroxide 5% gel with adapalene 0.1% gel in Asian acne patients: efficacy and tolerability

Background  Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability.
Objectives  To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris.
Methods  Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe).
Results  Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions.
Conclusion  Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris.

Conflicts of interest

None declared     

Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed‐dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter,randomized, investigator‐blind,parallel‐group study

Adapalene 0.1% (ADA) with clindamycin phosphate 1.2% (CLNP; ADA + CLNP) and the fixed‐dose combination containing CLNP and benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended for the early treatment of acne vulgaris in Japan. Here, we compare the early efficacy and safety of CLNP/BPO 3% with Japanese standard topical use of ADA + CLNP in the treatment of acne vulgaris. In this phase IV, multicenter study, 351 patients were randomized to receive CLNP/BPO 3% or ADA + CLNP for 12 weeks. The primary end‐point was percentage change from baseline in total lesion (TL) counts at week 2. Secondary end‐points included the percentage change from baseline in TL, inflammatory and non‐inflammatory lesion (IL and non‐IL) counts, Investigator's Static Global Assessment (ISGA), quality of life (QoL [Skindex‐16]) and patient preference. Local tolerability scores and adverse events were also recorded. CLNP/BPO 3% provided a significantly greater percentage reduction from baseline in TL compared with ADA + CLNP at week 2, and week 4. Compared with ADA + CLNP, CLNP/BPO 3% was superior at reducing IL (but not non‐IL) over weeks 2–12, was more effective at improving patient QoL and ISGA, and scored higher in patient‐preference assessments. Both treatments were well tolerated; adverse drug reactions occurred more frequently in patients receiving ADA + CLNP (37%) than in those receiving CLNP/BPO 3% (17%). In conclusion, CLNP/BPO 3% showed greater efficacy for the early treatment of acne vulgaris in Japan, with a more favorable safety profile compared with ADA + CLNP.     

Benzoyl peroxide, adapalene, and their combination in the treatment of acne vulgaris

Benzoyl peroxide and adapalene are among the most effective topical agents used in the treatment of acne. We planned an open-labeled, prospective study to compare the effects and side effects of these two drugs alone and in combination in the treatment of acne vulgaris. One hundred and five consecutive patients (30 men and 75 women) with acne vulgaris were included in this study. The patients were randomly divided into three groups with 35 patients in each. The groups were randomly assigned to 0.1% adapalene gel, 5% benzoyl peroxide lotion, or combination of 0.1% adapalene gel +5% benzoyl peroxide treatment. Acne lesions were classified as noninflammatory (open and closed comedones) and inflammatory (papule, pustule, nodule, cyst), and the lesions on the face were counted before the therapy, during the control visits, and after the treatment. Erythema, dryness, burning, and other side effects were recorded during the treatment. The mean age of the patients was 18.44 +/- 3.75 years. Eight patients were excluded because of noncompliance with the treatment regimen or the follow-up schedule, and four patients were excluded due to allergic contact dermatitis. The study revealed that all three therapy protocols were effective in treating noninflammatory and inflammatory lesions in acne vulgaris (p<0.05) and that there was no significant difference between the groups in efficacy or side effects (p>0.05). Adapalene and benzoyl peroxide are effective and well tolerated agents for acne vulgaris; combination therapy has no superiority over adapalene or benzoyl peroxide alone.     

Efficacy of the addition of salicylic acid to clindamycin and benzoyl peroxide combination for acne vulgaris

Clindamycin phosphate (CDP), benzoyl peroxide (BPO) and salicylic acid (SA) are known to be effective acne therapy agents depending on their anti-inflammatory and comedolytic properties. The purpose of this study was to investigate the efficacy and tolerability of the addition of SA treatment to CDP and BPO (SA and CDP + BPO) and compare it with CDP + BPO in patients with mild to moderate facial acne vulgaris. Forty-nine patients were enrolled in a 12 week prospective, single-blind, randomized, comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurements of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts. There were statistically significant differences between treatment groups for reductions in NIL counts beyond 2 weeks, IL counts and TL counts throughout the all study weeks, and global improvement scores evaluated by patients and investigator at the end of the study in favor of SA and CDP + BPO treatment when compared to CDP + BPO treatment. Both combinations significantly decreased stratum corneum hydration, although skin sebum values decreased with SA and CDP + BPO treatment. These combinations were also well tolerated except significantly higher frequency of mild to moderate transient dryness in patients applied SA and CDP + BPO. The addition of SA to CDP + BPO treatment demonstrated significantly better and faster results in terms of reductions in acne lesion counts and well tolerated except for higher frequency of mild to moderate transient dryness.     

0.1%阿达帕林凝胶和1%克林霉素溶液联合外用治疗寻常痤疮临床观察

目的:比较0.1%阿达帕林凝胶(达芙文)与1%克林霉素磷酸酯溶液(特丽仙)联合外用与特丽仙单用治疗寻常痤疮的疗效和安全性。方法:将300例中至重度寻常痤疮患者分为两组,试验组联合外用达芙文和特丽仙,对照组单用特丽仙,两组共治疗12周。结果:274例患者完成治疗,治疗4周后试验组皮损总数改善显著优于对照组(P<0.05),并维持至12周;治疗8周后试验组炎性皮损和非炎性皮损改善优于对照组(P<0.01),并维持至12周。治疗结束后试验组和对照组的有效率分别为84.40%和72.93%(P<0.05)。试验组局部刺激反应发生率为4.0%,对照组为8.7%。结论:达芙文联合特丽仙治疗中至重度寻常痤疮的疗效比单用特丽仙的效果好。     

Adapalene–benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients

Background  Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed-dose combination gel with adapalene 0·1% and benzoyl peroxide (BPO) 2·5% has recently been developed for the once-daily treatment of acne.
Objectives  To evaluate the efficacy and safety of adapalene 0·1%–BPO 2·5% fixed-dose combination gel (adapalene–BPO) relative to adapalene 0·1% monotherapy (adapalene), BPO 2·5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris.
Methods  In total, 1670 subjects were randomized in a double-blind controlled trial to receive adapalene–BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events.
Results  Adapalene–BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild-to-moderate dry skin), occurred early in the study, and were transient.
Conclusions  Adapalene–BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.     

Relationship between sebostatic activity, tolerability and efficacy of three topical drugs to treat mild to moderate acne

BACKGROUND: Acne is a multifactorial disorder in which the sebum plays an important pathogenetic role. PURPOSE OF THE STUDY: To evaluate the sebostatic effect of three anti-acneic ingredients (azelaic acid, adapalene and benzoyl peroxide) conveyed in cream and to determine whether there is a correlation with the therapeutic results. MATERIALS AND METHODS: Sixty-five patients with mild or moderate acne localized on the face were divided into three therapy groups at random: 25 applied azelaic acid once a day, 20, benzoyl peroxide and 20, adapalene. All the patients were observed at the time of enrolling and a further four times at fortnightly intervals. At each visit the sebum casual level on the forehead, chin and one cheek was measured using a sebumeter. Furthermore, side-effects and clinical-therapeutic effectiveness were noted. RESULTS: Four patients did not complete the study. Azelaic acid showed an average reduction of 13.9% in sebum production on the forehead, 14.2% on the chin and 15.2% on the cheek. Benzoyl peroxide caused an increase of 10.5% in sebum production on the forehead, 10.3% on the chin and 25.4% on the cheek. Adapalene reduced sebaceous secretion by 0.2% on the forehead and 6.7% on the cheek whereas sebum production increased by 6.2% on the chin. All three drugs showed a clinical improvement in the acneic lesions with moderate adverse effects. CONCLUSION: The three topical drugs bring about good therapeutic results with scarce side-effects that do not, however, seem to be correlated with the sebostatic activity.     

A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris

BACKGROUND: A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris. OBJECTIVES: We aimed to follow up this study. METHODS: The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris. RESULTS: At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated. CONCLUSIONS: A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.     

0.1%阿达帕林凝胶预防和减轻寻常痤疮复发的多中心随机对照临床试验

目的评价0.1%阿达帕林凝胶维持治疗对于预防和减轻寻常痤疮复发的作用.方法采用多中心、区组随机、开放、对照的方法,共入选患者246例,均为经过阿达帕林和克林霉素(特丽仙)联合治疗或特丽仙单独治疗获得有效(改善≥25%)的寻常痤疮患者,随机分为两组,一组外用0.1%阿达帕林凝胶,另一组不用药,均观察12周.结果239例患者完成治疗和观察,阿达帕林组121例,对照组118例.治疗4周后阿达帕林组炎性皮损数的减少显著优于对照组(P＜0.05),并维持至12周;治疗8周后阿达帕林组皮损总数和非炎性皮损数的减少也显著优于对照组(P＜0.01),并维持至12周.治疗结束后,阿达帕林组总体改善率为66.9%,对照组为4.2%(P＜0.01);阿达帕林组总复发率为4.1%,对照组为83.9%;两组间差异有显著性(P＜0.01).阿达帕林组有个别病例有轻度局部刺激反应,两组间不良反应差异无显著性(P＜0.05).结论阿达帕林凝胶可有效地治疗寻常痤疮,并维持治疗效果,且不增加局部刺激反应,对于减少病情复发具有显著效果.     

Clinical efficacy and safety of benzoyl peroxide for acne vulgaris: Comparison between Japanese and Western patients

Benzoyl peroxide (BPO) has been well established as a common medication for acne vulgaris in many countries (e.g. in Europe and the USA), where clinical data have been accumulated over a long time. In Japan, the use of BPO for acne treatment was approved in 2014, and the results of clinical trials in Japanese patients have recently been reported. This review compares clinical study results between Japanese and Western patients. Clinical studies that had been performed in Western countries were searched on the basis of the criteria, double‐blind studies of BPO monotherapy and comparison with a vehicle group. Two reports of Japanese studies were also selected by using the same criteria. Efficacy was assessed by comparing the mean difference between the BPO and the vehicle groups for reduction rate in the number of lesions from baseline, and there were no differences between Japanese and Western patients. Safety assessment also showed that the incidence of adverse events was higher in Japanese patients than in Western patients, but the characteristics of the adverse events were not different. Therefore, we conclude that there are no significant differences in the efficacy and safety of BPO between these patient populations. The efficacy and safety of long‐term use in Japanese patients are also expected to be applicable to those in Western patients.     

Skin tolerability and efficacy of combination therapy with hydrogen peroxide stabilized cream and adapalene gel in comparison with benzoyl peroxide cream and adapalene gel in common acne. A randomized, investigator-masked, controlled trial

BACKGROUND: Combination therapy with antiseptics such as benzoyl peroxide (BP) and topical retinoids is widely used as first-line treatment for acne vulgaris (AV). However, these combinations could have a suboptimal skin tolerability. Recently, a new formulation of hydrogen peroxide (HP) 1% in stabilized cream (Crystacide; Mipharm, Milan, Italy) became available. A previous clinical study has shown that HP cream monotherapy presents a better skin tolerability in comparison with BP in patients with mild AV. OBJECTIVES: To evaluate the tolerability and the efficacy of combination therapy with HP cream and adapalene 0.1% gel in comparison with the combination of BP 4% cream and adapalene 0.1% gel in the treatment of mild to moderate AV. METHODS: In a randomized, investigator-blinded trial, 52 patients (mean +/- SD age 25 +/- 6 years; 19 men and 33 women) with AV were randomly assigned to HP cream and adapalene gel (group HP + A) or to BP cream and adapalene gel (group BP + A), for eight consecutive weeks. Efficacy was assessed by total (TL), inflammatory (IL) and noninflammatory (NL) lesion counts performed at baseline and weeks 4 and 8. Tolerability was assessed by evaluating skin erythema, burning and dryness at weeks 4 and 8. RESULTS: All patients completed the study. At baseline, the mean +/- SD numbers of TL, IL and NL were 44 +/- 9, 25 +/- 7 and 19 +/- 6 in group HP + A and 40 +/- 9, 21 +/- 7 and 19 +/- 9 in group BP + A, respectively. At the end of the treatment period, TL, IL and NL were reduced by 93%, 92% and 95%, respectively, in group HP + A and by 88%, 86% and 90%, respectively, in group BP + A. A significantly (P = 0.0025) greater reduction in NL was observed in group HP + A in comparison with group BP + A. Tolerability was significantly better in group HP + A in comparison with group BP + A (P = 0.02). Skin dryness and burning sensation were more frequent in group BP + A. CONCLUSIONS: The combination of adapalene and HP cream is an effective topical treatment regimen in mild to moderate AV. This combination has shown a better tolerability profile in comparison with the combination of BP and adapalene.     

Efficacy of combined topical treatment of acne vulgaris with adapalene and nadifloxacin: a randomized study

Topical retinoid and antibiotic combination therapy is an integral part of acne treatment and is considered the appropriate first-line therapy according to the Japanese guideline for moderate and severe acne. In this combination, clindamycin or doxycycline are mostly used as antibiotics, but there have been no reports on the effectiveness of nadifloxacin, a widely used antibiotic in Japan and European countries for acne, in combination with topical retinoid. To confirm the efficacy and safety of adapalene gel and nadifloxacin cream in the treatment of Japanese patients with acne vulgaris, a total of 50 patients were randomized to the two groups, the combination therapy and the adapalene monotherapy, and each therapy was tested for 8 weeks. The percentage reduction in the number of inflammatory acne lesions was evaluated and the safety was monitored through adverse events. The combination of adapalene gel and nadifloxacin cream produced a significantly higher reduction in the inflammatory lesions at 2 weeks (P = 0.047) and at 8 weeks (P = 0.011) after the starting than did adapalene gel monotherapy. The combination did not elevate the side effects of erythema and scale scores, but rather significantly depressed erythema at 1 week. This study showed the efficacy and safety of the combination therapy of nadifloxacin cream with adapalene gel for the inflammatory acne.     

Pivotal clinical trials of adapalene in the treatment of acne

Adapalene, a naphthoic-acid derivative, possesses some of the biological activities of tretinoin but has distinct physicochemical properties and binding properties for selective affinity for retinoic acid receptors. As such, adapalene is less likely to be associated with certain local tolerability problems (e.g. burning, erythema, pruritus).
Over the past 5 years, numerous clinical trials have been conducted to compare the efficacy and tolerability of adapalene and tretinoin in the treatment of acne vulgaris. Three pivotal, large, well-controlled studies involving almost 900 patients showed that adapalene gel 0.1% and adapalene solution 0.1% are at least as effective as tretinoin gel 0.025%, with superior local tolerability. Adapalene cream 0.1% has proven to be significantly more effective than vehicle, with response rates comparable to those observed with the gel and solution. A meta-analysis of trials with the gel formulation confirmed these findings, showing equivalent efficacy and improved tolerability vs. tretinoin gel 0.025%. Moreover, the onset of clinical effect was shown to be significantly more rapid than that of tretinoin gel. Taken together, these studies demonstrated that adapalene has overall efficacy similar to that of topical tretinoin, but with a superior therapeutic ratio that may result in superior outcomes in clinical practice through improved compliance. This may be expected because of its lesser potential for skin irritation, especially early in treatment, and because of greater convenience in that no waiting period is required between face washing and application of the product. Therefore, 5 years of clinical experience have established that adapalene in its various formulations is a valuable addition to current treatments for acne vulgaris.     

Randomized study comparing the efficacy and tolerance of a lipophillic hydroxy acid derivative of salicylic acid and 5% benzoyl peroxide in the treatment of facial acne vulgaris

Background  New topical treatments for acne vulgaris are needed for patients who have tolerance problems with current treatments.
Aims  To compare the efficacy and tolerance of a lipophillic derivative of salicylic acid (lipo hydroxy acid or LHA) containing formulation and 5% benzoyl peroxide in subjects with acne vulgaris.
Methods  Eighty subjects with mild to moderate facial acne were randomized to receive either the LHA formulation twice a day or benzoyl peroxide once a day for 12 weeks. Efficacy and tolerance were evaluated at days 0, 28, 56 and 87.
Results  LHA formulation and benzoyl peroxide decreased the number of inflammatory lesions from baseline to week 12 by 44% and 47% and noninflammatory lesions by 19% and 23%, respectively. There was no statistically significant difference between the two treatments ( P =  0.748; P  = 0.445).
Conclusion  These results suggest that the LHA formulation could be a treatment option to consider in mild to moderate acne vulgaris patients that are intolerant to benzoyl peroxide.     

Control of microcomedone formation throughout a maintenance treatment with adapalene gel, 0.1%

BACKGROUND: Microcomedones representing the clinically non-visible central precursor lesions of acne are induced by sebaceous hyperplasia as well as altered follicular growth and differentiation, and evolve into both comedones and inflammatory lesions. Thus, targeting microcomedone formation is essential in the prevention and therapeutic control of acne. OBJECTIVE: The aim of this study was to assess the capacity of adapalene gel, 0.1%, to control the number of microcomedones after a combination treatment followed by a maintenance treatment. METHODS: This was a single-site exploratory study in subjects with a diagnosis of mild to moderate acne vulgaris and the presence of at least 250 microcomedones per cm(2) at screening visit, counted via cyanoacrylate strips (CyASt). During the first 8 weeks, a combination of adapalene gel (0.1%) and benzoyl peroxide gel (2.5%) was applied. During the randomized, investigator-blinded, and vehicle-controlled 12-week maintenance phase, adapalene once daily (QD), or adapalene alternately with its vehicle once daily every other day (QoD), or vehicle QD were applied to the face. CyASt sampling on the forehead was done at baseline, week 8, and week 20. Lesion counting allowing calculating a defined success rate was done at all visits. RESULTS: A total of 54 subjects entered the combination phase, and 49 subjects were randomized into the maintenance phase: 16 in both the adapalene QD and the QoD group and 17 subjects receiving the vehicle. The microcomedone median count decreased for all groups until week 8 (end of combination phase) from 319 to 157. Microcomedone counts at the end of the maintenance phase (week 20) showed a significant percent difference (P = 0.04) between adapalene QoD (-53.5) and the vehicle (-42.1) and between adapalene QD (-50.6) and the vehicle (P = 0.037) compared with baseline. CONCLUSION: The application of adapalene gel, 0.1% monotherapy daily, or alternately every other day, significantly helps to control the microcomedone count during a 12-week maintenance treatment after a previous combination therapy with benzoyl peroxide in patients with mild to moderate acne.