Adapalene gel 0.1% is effective and safe for Japanese patients with acne vulgaris: a randomized, multicenter, investigator-blinded, controlled study

BACKGROUND: Topical retinoids, such as adapalene, are an integral part of acne therapy in most regions and are considered appropriate first-line therapy by international guidelines for all cases of acne with the exception of the most severe. However, there are currently no topical retinoids available for the treatment of acne vulgaris in Japan. OBJECTIVE: To confirm efficacy and safety of adapalene gel 0.1% versus the corresponding gel vehicle in the treatment of Japanese patients with acne vulgaris for up to 12 weeks. METHODS: A total of 200 patients were randomized to receive adapalene gel 0.1%, or vehicle once-daily for 12 weeks. Percent reduction in lesion counts (total, inflammatory, and non-inflammatory) and subject satisfaction were evaluated. Safety was monitored through adverse events and laboratory tests. RESULTS: Adapalene gel 0.1% produced significantly better reductions in total (P<0.0001), inflammatory (P=0.0010), and non-inflammatory lesions (P<0.0001) at endpoint (week 12, last observation carried forward) than gel vehicle, with a higher overall subject satisfaction. The primary efficacy variable, the median percent reduction of total lesion counts at endpoint, was significantly greater with adapalene gel 0.1% (63.2%) compared to that with the vehicle (36.9%) in the ITT population (P<0.0001). Significantly greater results were observed as early as week 1. Adapalene was well tolerated, with adverse events that were mostly mild-to-moderate and transient in nature. CONCLUSIONS: Adapalene gel 0.1% was effective in the treatment of acne vulgaris in Japanese patients. Adapalene was safe and well tolerated, consistent with the good tolerability profile demonstrated in other patient populations.     

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 Retinoids in Acne Vulgaris

Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.     

The efficacy and safety of adapalene gel 0.3% in the treatment of acne vulgaris: A randomized, multicenter, investigator-blinded, controlled comparison study versus adapalene gel 0.1% and vehicle

A randomized, multicenter, investigator-blinded, active- and vehicle-controlled study was conducted to evaluate the efficacy and safety of adapalene gel 0.3% versus adapalene gel 0.1% and the corresponding gel vehicle. Subjects were assigned randomly to receive either adapalene gel 0.3%, adapalene gel 0.1%, or vehicle once daily for 12 weeks. A total of 214 subjects with moderate to moderately severe acne vulgaris were enrolled, and 85% of subjects completed the study. Adapalene gel 0.3% was significantly superior to adapalene gel 0.1% in total and noninflammatory lesion counts and in global severity score (P < .05 for all). A concentration-dependent increase in clinical benefit for all efficacy assessments was observed. As expected, there were also statistically significant differences in all efficacy parameters in the adapalene gel 0.3% group relative to the vehicle group (P < .001 for all). Treatment-related adverse events were mostly mild-to-moderate and similar between active groups. The results of this study show that adapalene gel 0.3% was superior to adapalene gel 0.1% and vehicle in the treatment of moderate to moderately severe acne while retaining a similar safety and tolerability profile to adapalene 0.1% gel.     

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.     

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

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

Adapalene 0.1% and benzoyl peroxide 2.5% as a fixed-dose combination gel is as well tolerated as the individual components alone in terms of cumulative irritancy

International guidelines recommend the combination of retinoids (e.g. adapalene, tazarotene) and benzoyl peroxide for treating acne because of their complementary mechanisms of action. A new fixed-dose combination gel of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% (adapalene/BPO*) is an effective acne treatment and offers the advantage of a once daily application. This paper reports the results of a cumulative irritancy study in healthy volunteers comparing adapalene/BPO to adapalene 0.1% and BPO 2.5% applied separately, BPO 10% gel, tazarotene 0.1% gel and the gel vehicle as a control.There was no significant difference between the mean cumulative irritation index (MCII) for adapalene/BPO and any test product except tazarotene 0.1% gel, which had a significantly greater MCII than all other test products (p < 0.05). This study showed that adapalene/BPO as a fixed-dose combination is as well tolerated as BPO 2.5% gel alone or adapalene 0.1% gel alone in terms of cumulative irritancy.*Epiduotrade mark, Galderma S.A.     

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。     

Comparison of topical retinoids in the treatment of acne

Topical retinoids are been used to successfully treat acne for almost 3 decades. At the beginning, a retinoid was a compound of similar structure and action to retinol (vitamin A).(1) Changes at the carboxylic end group, the polyene chain, and the aromatic ring can result in the modification of the original molecule. To date, three generations of retinoids have been developed: the nonaromatics (retinol, tretinoin, and isotretinoin), the monoaromatics (etretinate and acitretin), and the polyaromatics (arotinoid, adapalene, and tazarotene). The new synthetic retinoid molecules have little resemblance with retinol but nonetheless are included in this family because they have the ability to bind with or activate retinoid receptors. Therefore, retinoids are vitamins and also hormones.(3)     

Topical Retinoids in Acne Vulgaris: A Systematic Review

Background

Topical retinoids are a first-line treatment for acne vulgaris.

Objective

This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris.

Methods

A PubMed and Embase search was conducted using the search terms ‘adapalene,’ ‘tretinoin,’ ‘tazarotene,’ and ‘acne vulgaris.’ Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria.

Results

Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator’s Static Global Assessment (24.1–28.8% and 13.3–17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1–34.9% vs 7–11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64–78.9% vs 41–56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012).

Conclusions

Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

     

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.     

Daily treatment with adapalene gel 0.1% maintains initial improvement of acne vulgaris previously treated with oral lymecycline

Topical retinoids are often recommended for preventing acne recurrence, but there are relatively few well-controlled maintenance studies published. The objective of the present study was to assess the maintenance effect of adapalene gel 0.1% relative to gel vehicle in subjects successfully treated in a previous 12-week adapalene-lymecycline 300 mg combination therapy study. This was a multicentre, investigator-blind, randomised, controlled study in 19 European centres. A total of 136 subjects with moderate to moderately-severe acne vulgaris who showed at least moderate improvement from baseline when treated with either adapalene plus lymecycline or lymecycline plus gel vehicle in a previous 12 week study were included. Subjects were randomised to receive adapalene gel 0.1% or vehicle once-daily for 12 weeks. Efficacy and safety criteria included maintenance rate, percent reduction in lesion counts (total, inflammatory, non inflammatory), global severity assessment, cutaneous tolerability, and adverse events. Adapalene provided better results relative to gel vehicle for all efficacy assessments. The maintenance rate for total lesions was 84.7% vs. 63.5% (P = 0.0049) with adapalene and the vehicle, respectively. Adapalene was safe and well tolerated in this study. This study demonstrates a clinical benefit of continued treatment with adapalene gel 0.1% as a maintenance therapy for acne.     

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.     

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.     

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 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.     

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.     

Spotlight on Adapalene in 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 favorable 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.     

Topical treatment in acne: current status and future aspects

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2-5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO(2) laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.