麻豆传媒

SAN FRANCISCO -- One-third of patients with moderate or severe acne in a large randomized trial had significant improvement in acne severity and lesion count with an antibiotic-free topical gel versus placebo, results showed.

After 12 weeks of treatment, 33.7% of patients treated with 0.3% adapalene/benzoyl peroxide (A/BPO) had at least a two-grade improvement in acne severity grade as compared with 11% of patients treated with a placebo gel. A subgroup analysis limited to patients with severe acne showed success rates of 31.9% with 0.3% A/BPO and 11.8% with the placebo.

Use of the A/BPO gel was associated with significantly greater reductions in the number of inflammatory and noninflammatory lesions, , of Gwinnett Clinical Research in Snellville, Ga., reported here at the American Academy of Dermatology meeting.

"This is the first time 0.3% adapalene has been combined with anything, but especially benzoyl peroxide, which in today's era of antibiotic stewardship, makes the most sense," Weiss told 麻豆传媒. "We're trying to use medications that may help us be better guardians of antibiotics and keep them useful for our patients who have acne and need them and for patients who don't have acne and need them."

"This study also was notable in that we broke out the severe patient population," he added. "We made sure we had as many moderate as severe patients, and these were truly severe patients. We found that the product worked well in both types of patients and independently in the severe population where we observed about a 75% lesion reduction over 12 weeks."

Both adapalene, a topical retinoid, and benzoyl peroxide, an anti-inflammatory and bactericidal agent, have long histories in the treatment of mild and moderate acne. A fixed-dose combination of (0.1% A/BPO, Epiduo) demonstrated safety and efficacy as treatment for moderate and severe acne. A 0.3% A/BPO formulation was developed more recently and showed promise in early trials of patients with moderate and severe acne.

Weiss presented data from a phase III, multicenter, randomized, vehicle- and active-control clinical trial involving patients with moderate or severe acne. Eligible patients were at least 12 years old and had a clinical diagnosis of acne with facial involvement, defined as at least 20 inflammatory lesions (papules/pustules) and 30 or more noninflammatory lesions (comedones).

Investigators randomized more than 500 patients in 3:3:1 ratio to 0.3% A/BPO, 0.1% A/BPO, or vehicle, applied once daily for 12 weeks. The trial had two prespecified study populations. The overall population comprised patients with investigator-assessed (IGA) acne grade 3 (moderate) or 4 (severe). The subgroup of patients with severe acne was designated as a secondary population of interest.

The trial had co-primary endpoints: success rate (at least two-grade improvement in IGA) and change in inflammatory and noninflammatory lesion count from baseline to 12 weeks. The trial was not designed or statistically powered to compare outcomes between the 0.1% and 0.3% treatment groups, said Weiss.

Data analysis included 503 patients. The results showed a significant difference in success rate in favor of the 0.3% A/BPO group versus placebo at 8 weeks (13.0% versus 3.1%, P=0.017), increasing to 33.5% versus 11.5% at 12 weeks and to 33.7% versus 11.0% (P=0.001) using multiple imputation methodology.

The difference in inflammatory lesion count achieved statistical significance within the first week (-21.3% versus -10.0%, P<0.001) and remained significantly different to the end of the study (-68.7% versus -39.2%, P<0.001).

In the subgroup of patients with severe acne, the 0.3% A/BPO group (n=106) had an unadjusted treatment success rate of 31.2% at 12 weeks versus 13.3% (P=0.029) in the vehicle group (n=34). The between-group difference remained similar after multiple imputation but was not statistically significant.

The inflammatory lesion count decreased by an average of 71.8% in the 0.3% A/BPO group at 12 weeks and 28.6% in the vehicle group (P<0.001) and remained significantly different by multiple imputation (-74.4% versus -33.0%, P<0.001). Similar to the overall analysis, the between-group difference in the severe subpopulation achieved statistical significance within a week of treatment initiation (-22.4% versus -9.8%, P≤0.003).

The 0.3% and 0.1% A/BPO formulations had similar safety profiles, said Weiss. In the 0.3% A/BPO arm, 15 adverse events occurred in 12 patients, and all 15 episodes were mild or moderate. One patient in the 0.3% A/BPO group discontinued treatment because of atopic dermatitis flare.

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