Recently, a number of promising study findings have been reported for treating acne and rosacea. In this update, we give you the highlights of some of the most interesting research that’s been presented at recent meetings, including this year’s annual meeting of the American Academy of Dermatology.

Phase III Study of Doxycycline as Rosacea Treatment
Evaluating the safety and efficacy of this treatment.
Results of a Phase III, double-blinded, placebo-controlled clinical study showed promising results of the safety and efficacy of doxycycline hyclate tablets (Periostat) 20 m.g. b.i.d. for the treatment of rosacea.

The study, which was presented by Dr. Diane M. Thiboutot at the Skin Disease Education Foundation’s Phoenix Dermatology Open Seminar in March, evaluated 134 patients and indicated that patients treated with doxycycline showed a continuous improvement during the 16-week course of the study compared to patients on placebo. The doxycycline patients had a significantly greater reduction in the number of inflammatory lesions (papules and pustules) compared to placebo. The improvement was clinically and statistically significant (p = 0.009).

The study also found that overall clinical disease severity based on the Clinician’s Global Severity Assessment Scale declined significantly in the doxycycline-treated group of patients compared to placebo, with a greater number of the doxycycline-treated patients showing a complete clearing of the disease at 16 weeks compared to the patients treated with placebo (p = 0.014).

The erythema in the doxycycline patients showed a trend toward greater improvement compared to patients in the placebo group (p = 0.08).

Measuring Facial Irritation After Rosacea Treatment
The effect of topical azelaic acid 15% gel.
In an effort to examine the frequently reported symptoms of stinging and burning following the application of topical medications, cosmetics and skincare products, Dr. Zoe Draelos examined the prevalence of lactic acid stingers among rosacea patients and explored the relationship between skin sensitivity, barrier function and efficacy in subjects treated with azelaic acid 15% gel (Finacea).

The study, a 14-day prospective trial conducted at a single center, had 40 female subjects in good general health with mild-to-moderate facial rosacea as judged by erythema, telangiectasia and inflammatory papules (15 or less inflammatory papules/pustules). For this study, patients were required to use only the provided facial rosacea medications as instructed. Exclusion criteria included any history of allergic responses to rosacea medications or any ingredients of the study product, pregnancy or lactation or participation in another research study.

At baseline, neurosensory perceptions were assessed through the lactic acid facial sting test, and skin barrier integrity was evaluated with transepidermal water loss (TEWL) and corneometry assessments. Also, a five-point assessment of rosacea was performed by investigators and subjects. All participants used AzA gel twice a day as directed for 14 days. All assessments were repeated on day 14.

The results were as follows:
• The lactic acid stinging assay found a high prevalence of skin sensitivity (62%) at baseline.
• No correlation between facial lactic acid stinging and facial stinging upon application of AzA gel — 20% reported a sensation of burning or stinging when they applied AzA gel and only 6 of 8 subjects who reported stinging had been identified as lactic acid stingers at baseline.
• Azelaic Acid gel didn’t cause any significant change in barrier function as determined by the TEWL measurements and skin hydration (corneometry).
• Treatment with AzA gel was effective in improving the symptoms of rosacea after 2 weeks of treatment. A statistically significant decrease in facial redness and global rosacea severity was noted in patients treated with the gel, as noted by the investigator and documented by photography.

Comparing Benzoyl Peroxide/Clindamycin and Placebo
How efficacious is this treatment for rosacea?
A study to compare the photographic results of patients treated with benzoyl peroxide /clindamycin 5%/1% (Benzaclin) and vehicle at baseline and end of treatment was found BP/C to be significantly more effective than vehicle in improving papules and pustules associated with rosacea.

Drs. James J. Leyden, Diane Thiboutot and Alan R. Shalita conducted this double-blinded, multicenter, placebo-controlled study for 12 weeks during which 53 patients were randomized to apply BP/C or placebo gel topically once a day to the face. Of the 53 patients, 27 used BP/C and 26 used placebo.

The three investigators independently evaluated changes in the number of papules and pustules from baseline to weeks 3, 6, 9 and 12 using the Overall Global Improvement (OGI) scale and the severity of papules and pustules from baseline to week 12 using the Overall Rosacea Severity Assessment (ORSA) scale. Reviewers rated photographs of the frontal, left and right views of patients taken at baseline and weeks 3, 6, 9 and 12.

All participants in the study were between the ages of 18 to 65 years with stage II rosacea according to the Plewig and Kligman classification system with eight to 50 combined facial papules/pustule with < 2 nodules. All patients had a minimum ORSA score of 2.5 and no significant disease or facial skin disease other than rosacea. Female participants needed to be postmenopausal for 1 year or longer, sterile or using birth control for more than 6 months before study entry.

According to the OGI scale, patients treated with BP/C experienced improvement from baseline at weeks 3 to 12, while patients receiving placebo showed no improvement or only slight improvement. A significant treatment difference (p < 0.001) adjusted for investigator was observed between the two groups. At week 12, 23% of patients in the BP/C group were rated at “clear or nearly clear” or as having “marked improvement” compared with 4% of the patients in the placebo group (p < 0.001).

According to the ORSA scale, patients treated with BP/C showed improvement for papular and pustular components at week 12 compared to baseline, while patients treated with placebo demonstrated no improvement or only slight improvement. A significant treatment difference (p < 0.001) adjusted for investigator was observed between the two groups. Significantly more patients treated with BP/C were rated as having “clear” or “minimal” rosacea at week 12 compared with patients in the placebo group (92% versus 67%; p < 0.001). See chart above.

Reducing Comedones in Acne Patients
The role of oral tazarotene.
A multicenter, double-blind, randomized, placebo-controlled, parallel-group phase II study, found that oral tazarotene (0.75 mg, 1.5 mg, 3 mg or 6 mg) (Tazorac) once a day for 24 weeks has shown anticomedonal activity and efficacy against nodulocystic lesions, papules and pustules. Patients participating in this study were over the age of 16 and had a presence of severe nodulocystic acne with at least seven nodulocystic facial lesions (>5 mm). All females had to have had a negative urine pregnancy test. Washout periods for this study included 7 days for vitamin A supplement > 5,000 IU/d, 14 days for topical and systemic antibiotics and topical acne treatments and 6 months for systemic retinoids.

Drs. Jerry K. L. Tan, Deborah A. Lew-Kaya and Patricia S. Walker conducted this study where 181 patients were randomized to placebo or oral tazarotene groups for 24 weeks. All patients were subsequently followed up for an additional 12 weeks after the active treatment phase. Patients were assessed at a screening visit and at weeks 0, 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, and 36.

Investigators found that once-daily oral tazarotene 3 mg or 6 mg reduced the numbers of non-inflammatory and inflammatory lesions. At week 24, 62% and 72% reductions in the numbers of comedones from baseline were observed with once-daily oral tazarotene 3 mg and 6 mg, respectively, while the reduction with placebo was 45%. There was a 61% and 55% reduction in the numbers of papular and pustular lesions observed at week 24 in the 3 mg and 6 mg oral tazarotene groups, respectively, with the reduction with placebo observed at 31%. After 24 weeks of treatment, there was a treatment success (> 50% global improvement) in 87% of patients treated with oral tazarotene 3 mg ( p < 0.01 vs. placebo) and in 89% of patients in the 6 mg group (p < 0.01 vs. placebo).

Reductions in the numbers of comedones, papules and pustules, and facial nodulocystic lesions were maintained during the post-treatment period or at close to the levels achieved after 24 weeks.

There were no statistically significant differences between groups in any adverse event, expect cheilitis (p < 0.05), which occurred more frequently in the oral tazarotene 1.5-mg to 6-mg groups than in placebo group.

Meta-Analysis in Acne Vulgaris
A look at the efficacy and tolerability of topical tazarotene.
Data from a six-study meta-analysis showed that topical tazarotene (Tazorac) is effective and well-tolerated in a broad range of patients with acne, regardless of their skin type, gender, race or the time of year treatment is given. Investigators, Drs. James J. Leyden, Nicholas J. Lowe, Alan Shalita and Guy Webster, used all available data from six multicenter, double-blind, randomized comparative studies involving monotherapy with tazarotene 0.1% gel or cream once a day for 12 weeks.

For all studies, patients were requested to wash their face with a gentle, non-medicated, non-soap cleanser about 15 minutes before applying a pea-sized amount of the study medication in a thin film covering their entire face. Participants could use a non-comedogenic moisturizer as needed. Results were analyzed by overall disease severity, skin type, gender, racial origin, and month in which treatment was initiated.

Data from 471 patients were analyzed. Overall, 88% of patients rated their tazarotene treatment as favorable to highly favorable at the end of treatment. Here’s a look at some highlights of the research.

Severity of Acne: Regardless of the severity or acne and whether the cream or gel was used, tazarotene was associated with a 50% to 75% global improvement by the end of treatment.

Skin Type: Efficacy of tazarotene gel didn’t appear to be influenced by the dryness or oiliness of patients’ skin (low patient numbers in some of the groups treated with the cream formulation prevented meaningful analyses of cream-specific data).

Gender: Tazarotene cream was equally effective in females and males, but tazarotene gel appeared to be significantly more effective in females than in males, especially against inflammatory acne.

Racial Origin: Treatment-related adverse events were comparable among patients regardless of racial origin, and there were no significant between-group differences in global response.

Seasonality: There didn’t appear to be any seasonal influence on the incidence of treatment-related adverse events for the gel or the cream.

Analysis of data led investigators to conclude:
• Topical tazarotene is effective and well tolerated in a wide variety of patients regardless of patients’ disease severity, skin type, gender or racial origin, and regardless of the time of year that therapy is initiated.

• Tazarotene gel and cream are effective in mild and moderate acne and in moderate-to-severe acne. Both the gel and cream are well tolerated in these patient groups and reduced mean levels of erythema below pre-treatment levels.

• Tazarotene helped to normalize dry skin, as well as the skin of patients with oily or mixed oily/dry skin.

• Tolerability is optimized with use of tazarotene cream rather than tazarotene gel, though in females with inflammatory acne whose top priority is efficacy, tazarotene gel is preferred.

Efficacy and Safety of Adapalene Gel 0.3%
A dose ranging study.
Researchers performed a multicenter, randomized, investigator-blinded, vehicle-controlled, balanced parallel group comparison study to evaluate the efficacy of adapalene gel 0.3% (Differin) compared to its gel vehicle and to assess the magnitude of treatment differences between the 0.3% and 0.1% gels. Investigators, Clark, Flores, Pariser, Jones, Wilson, Tschen, Liu and Graber, also evaluated the local tolerability and systemic safety profile of adapalene gel 0.3% compared to the 0.1% formulation.

For this study, 214 patients aged 12 to 45 years were randomized into three groups: 70 in the adapalene gel 0.3%, 70 in the adapalene 0.1% and 74 in the gel vehicle group.

Efficacy evaluation was based on total lesion count, inflammatory lesion count, non-inflammatory lesion count, Global Severity Score (GSS) for acne (Leeds Revised Acne Grading System) and facial oiliness. Safety evaluation was based on reporting of adverse events and routine laboratory parameters, including adapalene plasma levels at selected sites.

Overall, adapalene gel 0.3% was more effective in the treatment of mild to moderate inflammatory acne than adapalene 0.1% and its corresponding vehicle.

Total Lesion Count. Treatment with adapalene gel 0.3% resulted in a greater reduction of the total lesion count compared with adapalene gel 0.1% and with the corresponding vehicle. Except for week 4, a significant difference
(p < 0.05) against the 0.1% gel could be shown for the 0.3% gel.
Inflammatory Lesion Count. After 12 weeks, reduction in inflammatory lesion counts were -58%, -49% and -35% for adapalene 0.3%, adapalene 0.1% and vehicle, respectively.

Non-Inflammatory Lesion Count. Patients in the adapalene gel 0.3% group saw a significantly superior (p < 0.05) reduction in non-inflammatory lesions at all visits except at week 4 compared to the 0.1% group.
Global Severity Score Improvement. Improvement in GSS from baseline to week 12 was seen in 64% of the patients in the adapalene gel 0.3% group, 58.5% treated with adapalene 0.1% and in 35.2% treated with the vehicle. The difference was significant between the 0.3% gel and the 0.1% gel from week 8 on (p < 0.01).

Facial Oiliness. A larger proportion of patients treated with adapalene gel 0.3% had no oiliness at week 12 compared to subjects treated with adapalene gel 0.1% or corresponding vehicle (39%, 29% and 24%, respectively.)

Safety: There were no notable differences in local tolerability and safety parameters between the adapalene gel concentrations. Dry skin was reported most often with 23% of the patients in the adapalene 0.3% and 19% of patients in the adapalene 0.1% group. There were no clinically significant shifts in laboratory parameters.

The Role of Benzoyl Peroxide in Treating Acne
An evaluation of the clinical value of this product.
Dr. James Q. Del Rosso presented a poster at the AAD to discuss the clinical value of benzoyl peroxide cleanser use, the impact of specific formulations, proper usage and “contact time” implications, drug deposition characteristics and clinical efficacy. The poster also looked at the role and positioning of benzoyl peroxide cleansers in combination with other therapeutic agents for the treatment of acne vulgaris, and the potential advantages of “leave-on” benzoyl peroxide applied using a pad formulation.

Reduction in Propionibacterium acnes and Inflammatory Acne Lesions. A double-blind, vehicle-controlled study (n=75) evaluated the effect of benzoyl peroxide 5% wash on lesion counts and P. acnes reduction. Patients used the cleanser wash formulation twice a day for 12 weeks. In the patients using the benzoyl peroxide cleanser as monotherapy, a 39% reduction in inflammatory lesions was observed, while <10% lesion reduction was seen in the vehicle group. Using microbiologic assays, a 46% reduction in P. acnes was seen after 2 weeks of benzoyl peroxide wash treatment alone.

The ability of benzoyl peroxide 10% to reduce P. acnes was also evaluated in patients treated twice a day for 2 weeks (n = 17). On day 5, P. acnes was reduced from a log count of 6.39 (2,450,000 organism count) to a log count of 5.18 (156,000 organism count), which is a 93.5% reduction in P. acnes. By day 15, a 97% P. acnes reduction was observed.

Combination Therapy. An investigator-blinded, controlled, 12-week evaluation established the clinical benefit and tolerability of benzoyl peroxide 6% cleanser when used in combination with a topical retinoid (n = 56). For this study, 30 patients received a combination of benzoyl peroxide 6% cleanser in the morning and tretinoin 0.1% microsphere gel in the evening, while 26 patients received tretinoin 0.1% microsphere gel only in the evening. Both groups were given a gentle, non-lipid facial cleanser in the morning and evening, except during the morning for the group using benzoyl peroxide in the morning. All patients were also told to use a non-comedogenic SPF 15 sunscreen in the morning about 5 minutes after facial washing with additional applications allowed as needed. Lesion counts, erythema associated with acne lesions and features of treatment-associated irritation, such as erythema, peeling and dryness were evaluated. After 12 weeks, patients in the combination group demonstrated a much greater reduction in inflammatory acne lesions than those treated with the topical retinoid alone. See table below.

Application, Contact Time and Removal Technique. Patients should be instructed to gently massage benzoyl peroxide cleanser into lightly moistened skin and allow a contact time of 20 seconds, followed by gentle rinsing. This approach has been shown to produce clinical benefit in studies, such as those described above.

Pads for “Leave-On” Application. A multicenter, consumer research guidance trial was completed to evaluate the potential benefits and drawbacks of benzoyl peroxide 3% pad formulation. Two patients groups were studied. Group one included 100 male and female patients aged 12 to 19 years with previous experience using other benzoyl peroxide products. Group two included 101 female patients aged 25 to 39 years. The study found the pad provides a “leave-on” formulation that effectively and evenly delivers drug to the treatment area, is convenient, easy to use, portable and well-accepted by patients based on usage testing. The study determined that 94.5% of both groups said that the product delivered even coverage of treatment area, 98.5% said it was easy to apply and 90.5% said the pad was gentle to skin.