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 and bacteriological evaluation of adapalene 0.1% gel plus nadifloxacin 1% cream versus adapalene 0.1% gel in patients with acne vulgaris

This multicenter, randomized parallel group study investigated the efficacy and tolerability of adapalene 0.1% gel plus nadifloxacin 1% cream (combination therapy) compared with adapalene gel (monotherapy) during 12‐week treatment of acne vulgaris. A total of 184 Japanese patients aged above 12 years with moderate to severe acne as indicated by the Japanese severity grading criteria were randomized to combination therapy (n = 84) and monotherapy (n = 100) groups, both having comparable demographic and baseline characteristics. Adapalene was applied only to inflammatory acne lesions in order to minimize skin irritation and ensure the treatment results. Efficacy and safety evaluations, treatment compliance and satisfaction with drug application were periodically monitored. The combination therapy provided a significantly greater efficacy than adapalene in decrement of inflammatory papulopustular lesions at 4 weeks and thereafter (P = 0.0056). The overall judgment of the therapeutic efficacy by the physician at the end of study revealed a significant difference (P = 0.02496) between the groups in favor of combination therapy. Dryness was reported in a greater proportion of patients undergoing monotherapy than combination therapy at weeks 2 and 4 (P = 0.04652). The patient self‐assessment in satisfaction with the drug application at the end of study revealed a significant difference (P = 0.00268) between the groups in favor of combination therapy. Among 76 strains of Propionibacterium acnes isolated from 87 patients, no strain was resistant to nadifloxacin. Thus, the simultaneous use of adapalene and nadifloxacin may provide an additive and complementary effect, resulting in clinical superiority and greater patient adherence compared to adapalene monotherapy.     

异维A酸软膏治疗寻常痤疮的多中心随机对照研究

目的评价异维A酸软膏治疗寻常痤疮的疗效和安全性。方法人组寻常痤疮患者240例,分别应用0．05%异维A酸软膏或0．05%维A酸乳膏,每晚1次,疗程8周。通过炎性皮损和非炎性皮损计数观察疗效,评价红斑、脱屑、烧灼感等局部不良反应。结果治疗8周,试验组皮损总数目从45．52±19．80减少至16．24±16．10,对照组皮损总数目从44．00±19．13减少至12．24±11．34,试验组有效率为69．75%,对照组有效率为80．51%,差异无统计学意义(P＞0．05),两组局部不良反应发生率差异无统计学意义(P＞0．05)。结论异维A酸软膏治疗寻常痤疮安全有效,其临床疗效及皮肤耐受性同0．05%维A酸乳膏相似。     

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。     

Multicenter randomized controlled trial on combination therapy with 0.1% adapalene gel and oral antibiotics for acne vulgaris: comparison of the efficacy of adapalene gel alone and in combination with oral faropenem

We conducted a randomized controlled trial in patients with acne vulgaris with moderate to severe inflammatory lesions. The patients were assigned to the following three treatment groups: group A received monotherapy with 0.1% topical adapalene gel for 4 weeks; group B received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 2 weeks followed by 0.1% topical adapalene gel alone for 2 weeks; and group C received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 4 weeks. The result of the analysis indicated that the percentage reduction in inflammatory lesion counts after 2 weeks of treatment was significantly higher in groups B and C than in group A (P < 0.05). After 4 weeks of treatment, group C showed significantly higher percentage reduction in inflammatory lesion counts than in groups A and B (P < 0.05), whereas no significant difference was noted between the latter two groups. Adverse reactions included dryness and irritation at the adapalene application sites that were observed in 10.1% of cases (16/158 patients) and diarrhea and loose stool because of oral faropenem that were observed in 7.5% of cases (8/106 patients). Taken together, our results suggest that combination therapy with oral antibiotics and adapalene results in earlier improvement in patients with moderate to severe inflammatory acne compared to the application of adapalene alone, and that 4 weeks of the combination therapy is preferable to 2 weeks of treatment.     

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     

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.     

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.     

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.     

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.     

异维A酸治疗中度寻常痤疮临床疗效观察

目的:评价异维A酸治疗中度痤疮的疗效和安全性。方法:采用随机、阳性药物平行对照的临床试验。试验组患者每日服用异维A酸(泰尔丝);对照组患者每日服用维胺酯,两组患者均治疗6周。治疗2、4、6周,对两组痤疮患者的粉刺、丘疹、脓疱、结节囊肿、皮脂溢出等评分比较。结果:试验组皮损的总评分差值从(0.2166±0.1291)分增至(6.2469±1.1826)分,对照组则从(0.1290±0.3191)分增至(5.6297±1.4489)分,两组间痤疮评分差值比较,差异有显著性。治疗结束时,试验组痊愈率和有效率分别为58.18%和100.00%,对照组分别为22.41%和82.75%,二组间疗效比较差异有显著性。试验组有23例患者出现局部不良反应,对照组有31例患者出现局部不良反应。结论:异维A酸治疗中度寻常痤疮疗效好于维胺酯。     

A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide and adapalene 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 noninflammatory lesions and minimize the development of antibiotic resistance. Retinoids and associated treatments also have anti-inflammatory activity and decrease microcomedo formation. To date, few direct comparisons of these different acne treatments have been conducted. OBJECTIVES: To compare the clinical effectiveness of two treatments for facial acne: a ready-mixed once-daily gel containing clindamycin phosphate 10 mg mL(-1) + benzoyl peroxide 50 mg mL(-1) (CDP + BPO; Duac; Stiefel, High Wycombe, U.K.) and a once-daily gel containing adapalene 0.1% (ADA; Differin; Galderma, Watford, U.K.). METHODS: In this assessor-blind, randomized study; 65 patients were treated with CDP + BPO once daily and 65 patients with ADA once daily. The treatment period was 12 weeks and lesion counts, acne grade 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 inflammatory and total lesion counts than ADA. A between-group comparison of the percentage change from baseline showed that CDP + BPO was statistically significantly superior to ADA from week 1 onwards both for inflammatory lesions (P < or = 0.001) and for total lesions (P < or = 0.004). While 76% of inflammatory lesions remained at week 2 for patients using ADA, in contrast, only 55% of inflammatory lesions remained at week 2 in the CDP + BPO group, resulting in a treatment effect of 1.38. Thus CDP + BPO removed 38% more inflammatory lesions than ADA at this timepoint. The trend in favour of CDP + BPO, although less marked, continued to the end of the study. CDP + BPO was better tolerated than ADA, with a greater proportion of ADA-treated patients experiencing treatment-related adverse events. Adjunctive topical or oral agents and their impact on acne were not studied in this trial. Due to product differences, this study could not be double blinded but was only single (assessor) blinded. CONCLUSIONS: CDP + BPO and ADA are both effective treatments for acne, but CDP + BPO has a significantly earlier onset of action, is significantly more effective against inflamed and total lesions and is better tolerated, which should improve patient compliance.     

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.     

An update of recent clinical trials examining adapalene and acne

Topical retinoids are a mainstay in the treatment of acne vulgaris. In the past these agents have been associated with irritant effects, however, newer generations of topical retinoids have emerged that have been designed to be less irritating. This paper focuses on the newer topical retinoid products, and specifically looks at adapalene and recent clinical studies that evaluate its efficacy and tolerability. Most of these studies evaluate adapalene in comparison with the new tretinoin formulations, which, like adapalene, have been designed to be less irritating than their predecessors. The various studies comparing the efficacy and tolerability of adapalene with the new formulations of tretinoin are described. A summary of the findings and their implications follows.     

Adapalene gel 0.1% vs ketoconazole cream 2% and their combination in treatment of pityriasis versicolor: A randomized clinical study

Pityriasis versicolor (PV) is a chronic superficial fungal infection. Management using azole drugs leads to drug resistance. The present study aimed to compare the clinical outcome of 0.1% adapalene gel vs 2% ketoconazole cream and their combination in PV. This randomized double‐blinded study was conducted on 90 PV patients divided into three equal groups. GI was treated with topical ketoconazole 2% cream twice daily and placebo, GII was treated with topical 0.1% adapalene gel twice daily and placebo and GIII was treated with topical combination of 0.1% adapalene gel (at night) and ketoconazole 2% cream (in the morning). All patients received medications for 4 weeks. Evaluation was done at 2 and 4 weeks and included clinical assessment, laboratory assessment, and patient satisfaction. We found that after 4 weeks of treatment, all groups showed significant improvement. There was better response in GIII in terms of lower rate of positive potassium hydroxide staining, higher rate of significantly improved cases and higher rate of well‐satisfied patients. However, the difference fell short of statistical significance. We concluded that a combination of adapalene gel and ketoconazole cream is very effective in treatment of PV with no or mild side effects.     

异维A酸隔日疗法和每日疗法治疗痤疮疗效比较

目的:观察异维A酸(泰尔丝)隔日疗法和每日疗法治疗痤疮的疗效,以及在保证疗效的前提下唾液腺分泌减少的发生率.方法:将受试者分为两组,即异维A酸隔日疗法B组(试验组)和每日疗法组(对照组).试验组中体重≥50kg者,隔日口服异维A酸10 mg,每日3次;体重＜50 kg者,隔日口服异维A酸10 mg,每日2次.对照组中体重≥50 kg者,每日口服异维A酸3次,每次10mg;体重＜50 kg者,每日口服异维A酸2次,每次10mg,两组患者疗程均为6周.结果:经过6周的治疗,试验组患者有效率为77.17%,对照组患者有效率为85.00%.第2、4、6周末时试验组和对照组患者唾液腺分泌减少的发生率分别为26%、31.25%、32.18%和28.87%、34.12%、48.68%.结论:异维A酸隔日疗法治疗痤疮的疗效与每日疗法相当,唾液腺分泌减少的发生率更低.