Comparison of adapalene 0·1% solution and tretinoin 0·025% gel in the topical treatment of acne vulgaris

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0·1% solution and tretinoin 0·025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution.
  Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.     

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.     

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.     

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%.     

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.     

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.     

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.     

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     

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.     

Comparison of micronized tretinoin gel 0.05% and tretinoin gel microsphere 0.1% in young adolescents with acne: a post hoc analysis of efficacy and tolerability data

Acne vulgaris is common in young adolescents. Retinoids are widely used but may be associated with poor tolerability. This post hoc analysis of 483 participants aged 10 to 14 years with mild to moderate acne compared efficacy and tolerability of once-daily treatment with micronized tretinoin gel 0.05%, tretinoin gel microsphere 0.1%, and vehicle over 12 weeks. In study 1, inflammatory and noninflammatory lesion reduction and treatment success was comparable between tretinoin gel 0.05% and tretinoin gel microsphere 0.1%. Inflammatory (46.3%) and noninflammatory (45.7%) lesion reductions with tretinoin gel 0.05% were significantly greater than vehicle (37.1% and 27.9%, respectively) (both P<.001). In study 2, inflammatory and noninflammatory lesion reductions and treatment success with tretinoin gel 0.05% (30.6%, 39.1%, and 19%, respectively) were significantly greater than vehicle (10.9%, 16.9% [both P<.001], and 4% [P=.008], respectively). Tretinoin gel 0.05% was significantly better tolerated than tretinoin gel microsphere 0.1% (P<.001); the majority of adverse events (AEs) were mild, occurring in the first 2 weeks. Fourteen percent of participants reported dry skin, 8% skin burning sensation, 5% erythema, and 5% dermatitis exfoliative with tretinoin gel 0.05% compared with 32%, 11%, 23%, and 23%, respectively, with tretinoin gel microsphere 0.1% (all P<.001, except skin burning sensation). In this secondary analysis of acne in young adolescents aged 10 to 14 years, micronized tretinoin gel 0.05% provided a comparable lesion reduction and treatment success versus tretinoin gel microsphere 0.1%, with a better cutaneous tolerability profile.     

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.     

Clinical efficacy of Velac®, a new tretinoin and clindamycin phosphate gel in acne vulgaris

Velac®, a new gel formulation containing both tretinoin (0.025%) and clindamycin phosphate (1.2%), is effective in acne vulgaris using a once daily application. The single formulation enhances compliance in young patients and improves the therapeutic results. Treatment with Velac was found to be more effective than tretinoin alone in inflamed lesions and at least comparable in open and closed comedones. In two of the three studies the overall acne severity grade was significantly more reduced when compared with tretinoin. Velac is also more effective than clindamycin alone in the treatment of the non-inflamed lesions. In the two multicentre studies the reduction of the overall acne severity grade was also more favourable for the new gel formulation. A more rapid response occurred with Velac than with either component used (clindamycin or tretinoin) alone.     

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.     

Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris

One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution. Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment. Both medications significantly reduced the numbers of papules and open and closed comedones. No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment. By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment. No patient was terminated from the study for side effects. Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.     

Double-blind,vehicle-controlled,multicenter comparison of two 0.025% tretinoin creams in patients with acne vulgaris

Background: Preclinical study and human patch tests indicate polyolprepolymer-2 may reduce cutaneous tretinoin-induced irritation. Objective: This study compared the clinical efficacy and safety of a 0.025% tretinoin cream containing polyolprepolymer-2 and its vehicle to a commercially-available 0.025% tretinoin cream. Methods: In this 12-week multicenter, double-blind, parallel group study in patients with mild to moderate acne, objective lesion counts and the investigators’ global evaluations evaluated efficacy. Subjective evaluations of skin irritation were used to study safety. Results: A total of 271 patients were enrolled. The active treatments demonstrated comparable efficacy that was statistically significantly greater than that of the vehicle. Safety evaluations of cutaneous and noncutaneous adverse events also indicated comparable results of the active treatments. Conclusion: The commercially-available 0.025% tretinoin cream and the 0.025% tretinoin cream containing polyolprepolymer-2 demonstrated comparable efficacy and safety. (J Am Acad Dermatol 1998;38:S24-30.)     

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.