Comparative tolerance of adapalene 0·1% gel and six different tretinoin formulations

Adapalene 0·1% gel (Differin® gel) is a recently introduced topical treatment for mild to moderate acne which has been demonstrated to be much better tolerated and at least as effective as tretinoin 0·025% gel. We compared the tolerance of adapalene 0·1% gel with six different formulations and concentrations of tretinoin. A total of 55 healthy human subjects were enrolled in two controlled, randomized, observer blinded, intraindividual comparison studies. In the first study, adapalene 0·1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0·025%, 0·05% and 0·1% cream, tretinoin 0·01% and 0·025% gel, and petrolatum (control). In the second study, adapalene 0·1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0·025%, 0·05% and 0·1% cream, tretinoin 0·1% gel microsphere, and petrolatum (control). In both studies, cumulative irritation scores helped to define three groups of common irritancy potential, with significant differences between each group. In study A, the three groups were in descending order of irritancy: tretinoin 0·1% cream and tretinoin 0·05% cream; tretinoin 0·025% gel, tretinoin 0·01% gel and tretinoin 0·025% cream; adapalene 0·1% gel and petrolatum (control). In study B, the three groups were in descending order of irritancy: tretinoin 0·1% cream; tretinoin 0·05% cream, tretinoin 0·025% cream and tretinoin 0·1% gel microsphere; adapalene 0·1% gel and petrolatum (control). The experimental results show that adapalene 0·1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0·01% to 0·1%.     

Adapalene 0·1% gel for the treatment of acne vulgaris: its superiority compared to tretinoin 0·025% cream in skin tolerance and patient preference

One hundred patients with acne vulgaris applied adapalene (Differin®) 0·1% gel to one side of their face and tretinoin 0·025% cream to the other once a day for 4 weeks; the side of application was determined by randomization code. Patient tolerance (assessed as the side of the face least irritated by drug application) was recorded weekly and patient preference (assessed as the preparation more easily spread, absorbed more quickly, smelled better, felt best on the skin and least greasy to the feel) at completion of the study. The investigator measured skin irritation weekly, scoring erythema, skin dryness, desquamation and burning/stinging on a 10-point scale.
  After each week of treatment, 64–68% of patients found adapalene 0·1% gel more tolerable than tretinoin 0·025% cream ( P < 0·05). At study completion, 65% of patients preferred adapalene 0·1% gel over tretinoin 0·025% cream ( P  = 0·003). An overall assessment showed adapalene 0·1% gel was significantly less irritating to the skin in terms of producing erythema, dryness, desquamation and burning/stinging, at Visits 2, 3 and 4 ( P < 0·02).
  Thirty-two patients experienced mild to moderately severe adverse events; three had adverse events considered to be drug related (two with skin discomfort; one with skin dryness). One patient stopped using the study drugs because of dry skin.
  This study showed that a majority of patients preferred adapalene 0·1% gel over tretinoin 0·025% cream and that it caused significantly less skin irritation.     

Evaluation of clinical efficacy and safety of adapalene 0·1% gel versus tretinoin 0·025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life

A randomized, multicentre, investigator-masked study was conducted in 105 patients with mild to moderate acne vulgaris to compare the efficacy and safety of adapalene 0·1% gel with tretinoin 0·025% gel after three months of treatment, with particular emphasis on reduction in inflammatory lesion counts after one week of treatment and impact on quality of life.
  In terms of efficacy, adapalene gel was found to be superior to tretinoin gel after one week of treatment, with respect to reduction in inflammatory lesion counts (32% vs. 17%, respectively; P  = 0·001), total lesion counts (28% vs. 22%, respectively; P  = 0·042) and global severity grade (28% vs. 16%, respectively; P  = 0·001). No significant difference between the two treatments was found after 12 weeks of treatment for any of these variables. Evaluation of facial skin tolerance parameters showed significant differences between the two treatments in favour of adapalene for dryness, erythema, immediate and persistent burning and pruritus for at least one time point. One patient in the adapalene group and three patients in the tretinoin group experienced medical events which lead to discontinuation of treatment (skin irritation; NS). Quality of life scores improved more rapidly in the adapalene group than in the tretinoin group, with significant differences ( P < 0·05) appearing at week 1 for questions related to problems with partners, close friends or relatives and to skin symptoms. There was also a significantly greater improvement in social and leisure activity in the adapalene group at week 12.
  Adapalene 0·1% gel reduced inflammatory and total lesion counts more rapidly than tretinoin 0·025% gel, and was also better tolerated. These differences appear to result in an earlier and greater quality of life improvement for the patients receiving adapalene.     

A comparison of the efficacy and tolerability of adapalene 0·1% gel versus tretinoin 0·025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials

The purpose of this meta-analysis was to determine if adapalene 0·1% gel (Differin®) provided superior efficacy and better tolerability than tretinoin 0·025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0·1% gel, 450 treated with tretinoin 0·025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran–Mantel–Haenszel test. All statistical tests were two-sided, with the 0·05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0·1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.     

Adapalene 0·1% gel has low skin irritation potential even when applied immediately after washing

The purpose of this study was to evaluate the difference, if any, in facial skin tolerance of adapalene 0·1% gel applied immediately after washing, compared to delayed application as recommended for the other topical retinoids: tretinoin and isotretinoin. Twenty-five acne patients with mild to moderate acne vulgaris were included in this intra individual randomized comparison study where adapalene 0·1% gel was applied immediately after washing on one half of the face and 20–30 min after washing on the contralateral half-face, for 22 consecutive days.
  No difference between the two regimens was detected by the investigator or by 21 of the 22 patients who completed the study. It was concluded that application of adapalene gel 0·1% is well tolerated even when applied immediately after washing.     

Adapalene 0·1% gel and adapalene 0·1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers

A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0·1% gel and adapalene 0·1% cream with their respective vehicles, using tretinoin 0·05% cream ( n  = 21) or tretinoin 0·1% cream ( n  = 9) and a tretinoin cream vehicle ( n  = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter.
  Adapalene 0·1% gel and adapalene 0·1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles ( P < 0·01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle ( P < 0·001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0·1% cream resulted in significant erythema.
  Adapalene 0·1% gel and adapalene 0·1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin.     

Randomised,controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris

BACKGROUND: Previous clinical trials have shown that adapalene gel produces less irritation than tretinoin gels and tretinoin 0.025% cream. Short term results have shown that adapalene is less irritating than tretinoin gels and creams. This study is the first to compare the 0.1% formulation of adapalene gel with the 0.05% strength of tretinoin cream in a formal clinical trial. OBJECTIVE: To investigate the efficacy and tolerability of adapalene gel 0.1% compared with tretinoin cream 0.05% in patients with mild-to-moderate acne vulgaris. METHODS: Ten-week, multicentre, randomised, investigator-masked, active-controlled, parallel group study in 409 patients with acne vulgaris. RESULTS: Adapalene gel 0.1% demonstrated equivalent efficacy in reduction of acne lesion counts and global improvement of acne severity over 10 weeks' treatment and was significantly better tolerated than tretinoin cream 0.05% in terms of erythema, dryness, desquamation and stinging/burning. CONCLUSION: Adapalene gel 0.1% showed equivalent efficacy and was significantly better tolerated than tretinoin cream 0.05% in patients with mild-to-moderate acne vulgaris.     

Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation

Adapalene and tretinoin are molecules used in the topical treatment of acne vulgaris. Commercial formulations (adapalene 0·1% gel and tretinoin 0·025% gel) were mixed with equal volumes of commercially available benzoyl peroxide formulation (10% lotion) and subsequently exposed to light over 24 h. With and without exposition to light, adapalene exhibits a remarkable stability whereas tretinoin is very sensitive to light and oxidation. The combination of benzoyl peroxide and light results in more than 50% degradation of tretinoin in about 2 h and 95% in 24 h.     

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.     

Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial

BACKGROUND: Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. OBJECTIVE: To compare the efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. METHODS: Eighty patients were enrolled and were instructed to apply adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. RESULTS: Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. CONCLUSIONS: The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids.     

Split-face clinical and bio-instrumental comparison of 0.1% adapalene and 0.05% tretinoin in facial acne.

BACKGROUND: Adapalene and tretinoin are topical compounds active for treating acne. OBJECTIVE: To compare the efficacity and safety of adapalene 0.1% gel and tretinoin 0.05% gel in moderately severe facial acne using clinical and objective biometrological assessments. Such information is currently lacking in the literature. METHODS: The split-face method was used in 25 acne volunteers for a 6-week treatment. In addition to clinical counts of lesions, the amount of comedones was assessed using computer-assisted morphometry of cyanoacrylate follicular biopsies. The erythema index and squamometry values were used to quantitate skin irritation. RESULTS: The tretinoin formulation brought better comedolysis and clinical improvement than the adapalene formulation. Erythema was transiently more pronounced on the tretinoin-treated side. Squamometry yielded no significant difference between both products. CONCLUSION: Tretinoin 0.05% gel exhibits a greater anti-acne efficacy than adapalene 0.1% gel, although with temperate tolerability.     

Topical retinoids in acne – an evidence‐based overview

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti‐inflammatory effects. The substances approved for acne treatment comprise tretinoin (all‐trans‐retinoic acid),isotretinoin (13‐cis retinoic acid) as well as the synthetic third‐generation polyaromatic retinoids adapalene and tazarotene,the latter being approved for acne treatment in the US only.Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild to moderate acne but differ in efficacy and tolerability. Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel or adapalene 0.1% gel or cream (EBM‐level 2c). Adapalene 0.1% is equally effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin 0.05% cream or isotretinoin 0.05% gel (EBM‐level 2c). Adapalene 0.1% gel is significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and tretinoin 0.05% gel, tretinoin 0.05% cream,tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel (EBM‐level 2c).The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dry‐ness,itching and stinging.The currently available evidence justifies the use of topical retinoids in most types of acne and during maintenance treatment.     

Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac®) and a proprietary 0.025% tretinoin gel formulation (Aberela®) in the topical control of facial acne

Background A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. Objective This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac®), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela®, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. Methods In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. Results CTG was statistically significantly more effective than tretinoin at the P= 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. Conclusion The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.     

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.     

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.     

Cumulative irritation potential of adapalene 0.1% cream and gel compared with tretinoin microsphere 0.04% and 0.1%

Despite the many beneficial effects of dermatologic applications, most of the current treatments for acne cause local irritation. The objective of this study was to compare the ability of the epidermis to tolerate adapalene 0.1% cream and gel and tretinoin microsphere in concentrations of 0.04% and 0.1%. A total of 31 subjects were enrolled in the study. The test products were applied under occlusive dressings on the upper back for approximately 24 hours, 4 times a week, and for 72 hours, once a week, for a period of 3 weeks. Skin reactions (erythema score plus other local reactions) at the product application sites were assessed 5 to 30 minutes after dressing removal. Twenty-six subjects completed the study. A total of 10 subjects discontinued use of 1 or more of the test products because of irritation scores reaching severe or greater, all of these discontinuations were at sites treated with the tretinoin products. The mean 21-day cumulative irritancy indices for adapalene 0. 1% cream and gel were significantly lower (P<.01) than those for tretirnoin microsphere 0.04% and 0. 1% and not higher than that of the negative control product.     

阿达帕林凝胶治疗寻常痤疮10年回顾

目的 总结阿达帕林凝胶治疗寻常痤疮的临床文献,为临床合理用药提供参考。方法 对阿达帕林凝胶上市10年来国内有关治疗寻常痤疮的疗效及安全性观察的中文文献进行整理和分析。结果 联合用药组疗效高于单用药物组,阿达帕林凝胶组疗效与其他维A酸类药物疗效相当,但高于其他痤疮药物组,不良反应低于其他药物。结论 阿达帕林凝胶治疗轻中度痤疮安全、有效,可单独或联合用药,还可作为维持治疗。     

Adapalene gel 0.1% in the treatment of infantile acne: an open clinical study

Abstract:  Infantile acne is an uncommon condition in pediatric age. We determined the efficacy and safety of adapalene gel 0.1% in the treatment of infantile acne. Twelve patients were enrolled for adapalene gel 0.1% application once daily over a 16-week treatment period. Efficacy evaluation included counting the inflammatory and noninflammatory lesions by the physician and global evaluation of the improvement. After 16 weeks all patients were followed up for a 1-year period. The time of clearance of the infantile acne lesions was 3 months in four (33%) patients and 4 months in eight (67%) patients (median 3.4 months). Adapalene gel produced reductions in noninflammatory and inflammatory lesions counts. Limited side effects were observed and none of them required stopping the therapy. No patient was left with scarring. Three patients were showed mild lesions in the 1-year follow-up period. Adapalene gel 0.1% was found to be a highly effective and safe drug in the treatment of mild-to-moderate infantile acne.     

Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel

Adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo?, Tactuo?) is the only fixed-dose combination product available that combines a topical retinoid with benzoyl peroxide; it targets three of the four main pathophysiologic factors in acne. This article reviews the therapeutic efficacy and tolerability of topical adapalene 0.1%/benzoyl peroxide 2.5% gel in the treatment of patients aged ≥ 12 years with acne vulgaris, as well as summarizing its pharmacologic properties. In three 12-week trials in patients aged ≥12 years with moderate acne, success rates were significantly higher with adapalene 0.1%/benzoyl peroxide 2.5% gel than with adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone, and combination therapy had an earlier onset of action. In addition, significantly greater reductions in total, inflammatory, and noninflammatory lesion counts were seen in patients receiving adapalene 0.1%/benzoyl peroxide 2.5% gel than in those receiving adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone. Adapalene 0.1%/benzoyl peroxide 2.5% gel did not significantly differ from clindamycin 1%/benzoyl peroxide 5% gel in terms of the reduction in the inflammatory, noninflammatory, or total lesion counts in patients with mild to moderate acne, according to the results of a 12-week trial. Twelve-week studies showed that topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral lymecycline was more effective than oral lymecycline alone in patients with moderate to severe acne, and topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral doxycycline hyclate was more effective than oral doxycycline hyclate alone in patients with severe acne. In patients with severe acne who responded to 12 weeks’ therapy with topical adapalene 0.1%/benzoyl peroxide 2.5% gel plus oral doxycycline hyclate or oral doxycycline hyclate alone, an additional 6 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel was more effective than vehicle gel at maintaining response, with further improvement seen in adapalene 0.1%/benzoyl peroxide 2.5% gel recipients. A noncomparative study also demonstrated the efficacy of 12 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel in patients with acne vulgaris. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in patients with acne. In 12-week trials, the most commonly occurring treatment-related adverse events included erythema, scaling, dryness, and stinging/burning; these dermatologic treatment-related adverse events were usually of mild to moderate severity, occurred early in the course of treatment, and resolved without residual effects. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in the longer term, with dry skin being the most commonly occurring treatment-related adverse event over 12 months of treatment. In conclusion, adapalene 0.1%/benzoyl peroxide 2.5% gel is a valuable agent for the first-line treatment of acne vulgaris.