have keratolytic and anti-inflammatory properties. They are also comedolytic, enhancing cellular differentiation and proliferation, normalizing desquamation and keratinization, and reducing cell cohesiveness within the follicle.21,26 Retinoids may be used as monotherapy or in combination with other topicals for both comedonal and inflammatory disease. Moreover, they are commonly used as maintenance therapy after initial control has been obtained over the acne.21,26 While effective, application site reactions such as dryness, peeling, redness, burning, and stinging are especially common in the first few weeks of therapy, a period known as “retinization.â€42 Various approaches have been taken to minimize these AEs, including initial intermittent use and application of moisturizers.43
Topical Dapsone
Dapsone is a sulfone antibiotic with anti-inflammatory properties. Topical dapsone 5% gel is approved by the US Food and Drug Administration (FDA) and commercially available to treat acne. While similar in name, the sulfone dapsone is structurally different to sulfonamide antibiotics. As such there is no allergic cross reactivity with sulfonamides, and a higher likelihood of someone with a known sulfa allergy being allergic to penicillin rather than to dapsone.44 The exact mechanism of action in treating acne is not clear. In vitro, dapsone has been demonstrated to inhibit neutrophil chemotaxis and release of lysosomal enzymes that promote inflammation and oxygen-free radicals. While dapsone is antimicrobial in treating leprosy, no activity has been shown against P. acnes.45 Data from the pivotal phase 3 clinical trials revealed that twice-daily use of topical dapsone was effective in treating both inflammatory and comedonal lesions (though with greater efficacy in inflammatory lesions), and it also had an extremely favorable tolerability profile.46 Moreover, topical dapsone has been successfully combined with other medications, such as topical retinoids and BPO.47,48
Dapsone is a sulfone antibiotic with anti-inflammatory properties. Topical dapsone 5% gel is approved by the US Food and Drug Administration (FDA) and commercially available to treat acne. While similar in name, the sulfone dapsone is structurally different to sulfonamide antibiotics. As such there is no allergic cross reactivity with sulfonamides, and a higher likelihood of someone with a known sulfa allergy being allergic to penicillin rather than to dapsone.44 The exact mechanism of action in treating acne is not clear. In vitro, dapsone has been demonstrated to inhibit neutrophil chemotaxis and release of lysosomal enzymes that promote inflammation and oxygen-free radicals. While dapsone is antimicrobial in treating leprosy, no activity has been shown against P. acnes.45 Data from the pivotal phase 3 clinical trials revealed that twice-daily use of topical dapsone was effective in treating both inflammatory and comedonal lesions (though with greater efficacy in inflammatory lesions), and it also had an extremely favorable tolerability profile.46 Moreover, topical dapsone has been successfully combined with other medications, such as topical retinoids and BPO.47,48
Newly Approved Topical Therapies
In the past year, 2 new fixed-dose combination topical products have been brought to market for the treatment of AV. Both demonstrate efficacy and tolerability across a variety of acne lesion types. The following summarizes the latest data on fixed-dose BPO 3.75%/clindamycin phosphate (CP) 1.2% gel and BPO 2.5%/ADA 0.3% gel.
Benzoyl Peroxide 3.75% /Clindamycin Phosphate 1.2% Gel
In November 2014, BPO 3.75%/CP 1.2% gel received FDA approval for the treatment of AV in patients 12 years of age and older. The vehicle is an aqueous gel with humectant properties and free from alcohol and preservatives.49 CP is the water soluble ester of clindamycin, which is fully dissolved in the aqueous gel base and readily available when applied to the skin. BPO is both microdispersed in the gel as well as micronized. It is evenly distributed in each metered dose, and 90% of the BPO particles are less than 10 microns in diameter.50 (As a point of reference, the hair follicle diameter for vellus hairs is estimated to be in the range of 130 microns.51)
In November 2014, BPO 3.75%/CP 1.2% gel received FDA approval for the treatment of AV in patients 12 years of age and older. The vehicle is an aqueous gel with humectant properties and free from alcohol and preservatives.49 CP is the water soluble ester of clindamycin, which is fully dissolved in the aqueous gel base and readily available when applied to the skin. BPO is both microdispersed in the gel as well as micronized. It is evenly distributed in each metered dose, and 90% of the BPO particles are less than 10 microns in diameter.50 (As a point of reference, the hair follicle diameter for vellus hairs is estimated to be in the range of 130 microns.51)
In the phase 3, pivotal clinical trial, 498 subjects were enrolled in a 12-week multi-center, double-blind, vehicle-controlled study. Patients were randomized 1:1 to receive either active drug or vehicle, which was applied once daily to the face. Standard washout periods for previous prescription and over-the-counter (OTC) products were enforced. Enrolled patients had a baseline Evaluator’s Global Severity Score (EGSS) of moderate or severe (EGSS = 3 or 4) and mean baseline lesion counts of 27 and 37.8 inflammatory and comedonal lesions, respectively.52
The drug was shown to be efficacious and statistically better than vehicle for all efficacy treatment variables. At week 12, the absolute change in inflammatory lesions was -16.3 lesions compared with baseline, while the comedonal lesions were reduced by 19.2 lesions. There was a 51.8% and 60.4% mean reduction in comedonal and inflammatory lesions, respectively. 35% of patients were considered a treatment success at week 12, with a 2-grade improvement in EGSS. 29% of patients were a treatment success with a greater than 2-grade EGSS improvement. In this case, for example, a patient would have had a baseline score of a 4 (severe) and improved at least 3 grades to 1 or 0 (almost clear or clear). A severe patient (EGSS = 4) who improved 2 grades to mild (EGSS = 2) was not included in this endpoint.52
BPO 3.75%/CP 1.2% gel was well tolerated. The most common AEs in the study, which occurred in less than 0.5% of subjects treated with the active drug, were application site reactions including burning, contact dermatitis, pruritus, and rash. No subjects in the active treatment arm discontinued the study due to an AE or a lack of efficacy. Cutaneous tolerability was similar between the active drug and the vehicle.49,52
Post-hoc analyses of the phase 3 data and phase 4 studies have provided additional data on BPO 3.75%/CP 1.2% gel. In one analysis, the drug was found to be effective and well-tolerated in the severe subpopulation of acne patients in the study. 55.1% of severe patients had at least a 2 grade improvement in EGSS at week 12, and 30.6% of severe patients were clear or almost clear.53 Additionally, it was found to be effective in adult women54 and in adolescents.55 Finally, BPO 3.75%/CP 1.2% gel was shown to have excellent cosmetic compatibility with facial foundation makeup in adult women.56
Benzoly Peroxide 2.5%/Adapalene 0.3% Gel
BPO 2.5%/ADA 0.3% fixed-dose combination gel received FDA approval for the treatment of acne in July 2015.57 This antibiotic-free option is the next generation of BPO 2.5%/ADA 0.1% gel that was approved for acne in 2009.58,59 An in vitro absorption study was performed comparing the fixed-dose combination gel to separate application of the monad drugs. The fixed-dose
BPO 2.5%/ADA 0.3% fixed-dose combination gel received FDA approval for the treatment of acne in July 2015.57 This antibiotic-free option is the next generation of BPO 2.5%/ADA 0.1% gel that was approved for acne in 2009.58,59 An in vitro absorption study was performed comparing the fixed-dose combination gel to separate application of the monad drugs. The fixed-dose
