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The Efficacy and Tolerability of a Fixed Combination Clindamycin (1.2%) and Benzoyl Peroxide (3.75%) Aqueous Gel in Adult Female Patients with Facial Acne Vulgaris

Joshua A. Zeichner, MD Mount Sinai Hospital, New York, New York

Disclosure: Dr. Zeichner is a consultant to Valeant.

Abstract

Objective: To investigate the efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle monotherapy in adult female acne patients. Methods: A post hoc analysis in 72 adult female patients (aged ?25 years) with moderate-to-severe acne receiving clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle for 12 weeks. Results: The efficacy of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel was significantly greater than vehicle. The mean percent change from baseline in inflammatory and noninflammatory lesion counts and the percentage of patients who achieved a 2-grade reduction in the Evaluator’s Global Severity Score was 68.7%, 60.4, and 52.7 percent, respectively (P=0.019, 0.020 and 0.074 versus vehicle). In addition, 44 percent of patients reported their acne to be “clear” or “almost clear” at Week 12 (P=0.026 versus vehicle). No substantive differences were seen in cutaneous tolerability among treatment groups, and no patients discontinued treatment because of adverse events. Limitations: It is not possible to determine the contributions of the individual active ingredients, and this study was not set up specifically to investigate the treatment of adult female acne. Conclusion: Clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel provides statistically significant greater efficacy than vehicle in treating acne in adult female patients and has a favorable safety and tolerability profile. (J Clin Aesthet Dermatol. 2015;8(4):21–25.)

Acne vulgaris is a very common skin disease that usually presents in adolescence, but frequently continues into adulthood. An increasing number of older women are seeking acne treatment from dermatologists.[1],[2] A recent study of almost 3,000 women taken from a general population showed that although acne peaked in teenage years, 45 percent of women aged 21 to 30, 26 percent aged 31 to 40, and 12 percent aged 41 to 50 suffered from acne.[3]

The pathogenesis of adult acne and its differences from that of teenage acne are unclear. In general, adult women with acne have high levels of sebum. Smoking has also been identified as an aggravating factor for patients with pre-existing acne or with a genetic predisposition.[4],[5] The majority of patients have a first-degree family history of postadolescent acne,[6] a factor known to increase the risk of adult acne by four percent.[7] Acne has been shown to be associated with psychiatric comorbidities in adult women. One study reported 40 percent of adult female acne patients suffer from depression,[8] and daily stress has been shown to exacerbate the condition.[9]

Postadolescent acne is broadly categorized into two main groups—persistent (the most common) and late-onset acne. Patients with persistent acne are those who developed acne in adolescence and the acne did not resolve.[10] Late-onset acne, on the other hand, refers to patients who were clear in their teenage years, but developed acne later in life. Traditionally, adult acne has been described as an inflammatory condition affecting predominantly the lower one-third of the face and jawline. Frequently, patients report a premenstrual flare occurring 1 to 2 weeks prior to menses. However, recent data now challenge this notion. In a recent international study evaluating 374 women, investigators found that in 90 percent of patients, facial acne distribution was similar to that of teenagers. Moreover, acne was characterized not only by inflammatory lesions, but also comedones.[11] A cross-sectional, web-based survey of 208 adult women revealed similar data, noting facial acne on the cheeks, chin, and forehead. This study also assessed disease burden, with three of four respondents reporting that their acne was moderately, severely, or very severely troublesome.[12]

Data on the treatment of acne in the adult female population is limited. Recently, efficacy and tolerability data on a new fixed combination product, clindamycin phosphate 1.2%/benzoyl peroxide (BP) 3.75% gel was reported.[13] A post hoc analysis was performed to evaluate efficacy and cutaneous tolerability of this product in adult female patients enrolled in the study.

Methods

Detailed methodology has already been reported elsewhere; however, a summary is provided below.[13]

Study design. A total of 498 patients with moderate-to-severe acne vulgaris were randomized (1:1) to receive clindamycin phosphate 1.2%/BP 3.75% gel, or vehicle in a multicenter, double-blind, controlled, 12-week study. Patients were stratified by severity of acne (Evaluator’s Global Severity Score [EGSS], ranging from 0 [clear] to 5 [very severe]). They were dichotomized into a moderate (EGSS of 3) and a severe acne group (EGSS of 4).

The post hoc analysis compared data between clindamycin phosphate 1.2%/BP 3.75% gel and vehicle in female patients aged ?25 years old.

Study population. Patients were included of any race or ethnicity with moderate-to-severe acne, defined as 20 to 40 inflammatory lesions (papules, pustules, and nodules), 20 to 100 noninflammatory lesions (open and closed comedones), and no more than two nodules. Standard washout periods were required for patients using previous prescription and over-the-counter acne treatments.

Efficacy evaluation. Efficacy evaluations included inflammatory and noninflammatory lesion counts and EGSS at screening, baseline, and during treatment (Weeks 4, 8, and 12). Primary efficacy endpoints included absolute change in mean inflammatory and noninflammatory lesion counts, and the proportion of patients who achieved at least a 2-grade reduction in EGSS from baseline to Week 12. Secondary efficacy endpoints included mean percent change from baseline to Week 12 in inflammatory and noninflammatory lesion counts and the proportion of patients who considered themselves “clear” or “almost clear” at Week 12 (Subject Self-Assessment [SSA]).

Safety evaluation. Cutaneous safety (erythema and scaling) and tolerability (itching, burning, and stinging) were evaluated at each study visit on a scale of 0 (none) to 3 (severe). Adverse events (AEs) were evaluated throughout the study.

Statistical analysis. The intent-to-treat (ITT) population comprised all patients randomized and provided with study drug. The safety population comprised all randomized patients who were presumed to have used the study medication at least once and who provided at least one post baseline evaluation.

The investigator assessments (EGSS, lesion counts) were conducted independently of the SSA. Statistical significance was based on 2-tailed tests of the null hypothesis resulting in P-values of 0.05 or less.

All AEs occurring during the study were recorded and classified on the basis of medical dictionary for drug regulatory activities terminology for the safety population. The Fisher exact test was used to compare the proportion of patients in each treatment group who reported any AE at a significance level of 0.05.

Results

Baseline characteristics. Overall, 72 female patients aged ?25 years were treated with clindamycin phosphate 1.2%/BP 3.75% gel (N=29) or vehicle (N=43) for 12 weeks.

Total lesion counts at baseline were 62.3 and 58.9 (active treatment and vehicle, respectively), with no significant difference between the two treatment groups. The majority of patients (N=55, 76.4%) had moderate acne. There were proportionately more severe acne patients (23.6%) in the adult female subgroup than in the total study population (17.3%). See Table 1 for baseline characteristics and patient disposition by treatment group.

Efficacy. In female patients aged ?25 years, efficacy results with clindamycin phosphate 1.2%/BP 3.75% gel were greater than vehicle for each of the primary and secondary endpoints, achieving statistical significance in mean lesion count reduction, mean percent lesion reduction, and SSA. Treatment success was numerically, but not statistically, greater in the active arm compared to vehicle.[13]

Lesion counts. The reduction in inflammatory and noninflammatory lesion counts was significantly greater with clindamycin phosphate 1.2%/BP 3.75% gel compared with vehicle. The absolute mean reduction in inflammatory and noninflammatory lesion counts with clindamycin phosphate 1.2%/BP 3.7% gel were 17.0 and 22.0 respectively compared to 9.6 and 10.1 with vehicle.

Mean percent change from baseline to Week 12 in inflammatory and noninflammatory lesion counts with clindamycin phosphate 1.2%/BP 3.7% gel was 68.7 and 60.4 percent, respectively, compared to 39.7 and 34.0 percent with vehicle (P=0.019 and 0.020, respectively, Figure 1).

Evaluator’s Global Severity Score (EGSS). Overall treatment success (?2 grade reduction in EGSS from baseline) with clindamycin phosphate 1.2%/BP 3.75% gel was achieved in 52.7 percent of adult female patients, compared to 30.0 percent with vehicle. This was numerically greater than, but not statistically different from, vehicle (P=0.074, Figure 2).

Subject Self-Assessment (SSA). At baseline, approximately 80 percent of female patients reported their acne covered at least 50 percent of their face. By Week 12, 44.0 percent of patients reported their acne to be “clear” or “almost clear” (<10%) using clindamycin 1.2%/BP 3.75% gel compared to only 13.5 percent using vehicle (P=0.026). More than 70 percent of patients reported at least a marked (?75%) improvement in their acne at Week 12 with active drug, twice that seen with vehicle over the same time period (Figure 3).

Safety. Overall, six (22.2%) patients treated with clindamycin 1.2%/BP 3.75% gel and seven (16.7%) patients treated with vehicle reported at least one AE. None were serious, and all were mild or moderate in severity. One reported AE in each treatment arm was related to study medication (burning sensation, contact dermatitis). Neither led to discontinuation from the study.

Cutaneous Tolerability Assessment. Overall mean scores for cutaneous safety (erythema and scaling) and tolerability (itching, burning, and stinging) at baseline and at each post-baseline visit were <1 (where 1=mild). There were no statistical differences between the clindamycin phosphate 1.2%/BP 3.75% gel and vehicle groups (data not shown). Almost 80 percent of patients reported no cutaneous tolerability issues at all throughout the study. There was only one report of moderate scaling and burning (a score of 2), and two reports of moderate itching over the 12-week treatment period with clindamycin phosphate 1.2%/BP 3.75% gel. The case of moderate scaling was reported at Week 4 and then improved. Moderate burning and itching were reported at the end of the study (Week 12).

No patient in the clindamycin phosphate 1.2%/BP 3.75% gel group experienced severe local signs or symptoms or discontinued study treatment because of AEs.

Discussion

Post-adolescent acne remains a challenge to treat. There is little data explaining why acne begins or persists in adulthood, why adult women are affected significantly more than men, and what etiological and aggravating factors are the most important. Acne in adult women has a significant impact on quality of life, is associated with depressive symptoms and anxiety, and negatively influences performance in the workplace.[12] Specific characteristics of acne in adult women must be considered when selecting a treatment regimen.[14] These include issues related to the skin and hormonal status of the patient as well as lifestyle issues and patient preferences. Finally, a simple regimen tailored to the patient’s needs encourages adherence to the regimen and will ultimately improve outcomes.[15]

Clindamycin phosphate 1.2%/BP 3.75% gel is a safe and effective treatment for a variety of acne patients and demonstrated patient satisfaction, with a reduction in the perception of facial skin oiliness.[13] In this post hoc analysis, adult women at least 25 years old with moderate-to-severe acne were evaluated. Similar to data seen in the overall population of the pivotal study, in this study clindamycin phosphate 1.2%/BP 3.75% gel was statistically more effective than vehicle in lesion count reduction, and more than 50 percent of patients achieved treatment success at Week 12. Almost 20 percent of patients reported a marked improvement in their acne as early as Week 2. More than 80 percent of the adult female patients had acne covering at least 80 percent of their face at the start of the study, and more than 70 percent reported at least a marked improvement in their acne by Week 12.

While an effective drug is important in an acne treatment, tolerability is as important as it drives treatment adherence. Especially in the adult woman, who is cosmetically camouflaging acne with makeup, medication tolerability and lack of skin irritation is paramount. Clindamycin phosphate 1.2%/BP 3.75% gel was well-tolerated in this patient population, with overall mean scores for erythema, scaling, itching, burning, and stinging reported as mild or none throughout the study. Moreover, there were no statistical differences in tolerability between patients in the active and vehicle groups.

There are limitations to this study. It is not possible to assess the contributions from the individual active ingredients, although previous studies with clindamycin/BP fixed combinations have demonstrated a synergistic effect.16 Also, these are data derived from the controlled setting of a clinical trial, which does not translate directly to the real-world clinical setting. Moreover, the pivotal study from which this analysis was performed was not set up specifically to study adult female acne patients, and as such the patient population in this post hoc analysis may not be representative of the typical female acne patient that presents in our practice. Future studies should be performed in adult women with acne to confirm these data.

Acknowledgment

The author acknowledges Brian Bulley, MSc, of Inergy Limited for medical writing support. Valeant Pharmaceuticals North America LLC funded Inergy’s activities pertaining to this manuscript.

references

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