acne-specific Investigator Global Assessment (IGA) scores. Their mechanisms of action and efficacies are reviewed next.
Azelaic Acid
Azelaic acid is a dicarboxylic acid that exhibits anti-inflammatory, anti-infective and skin lightening properties.56 Three studies have assessed azelaic acid foam and cream for truncal acne. Hoffman et al performed a 16-week open-label study utilizing azelaic acid 15% foam in 18 patients and found that 44% achieved a rating of clear or almost clear.57 Kainz et al also found improvement with azelaic acid 20% cream in a 12-week non-interventional study of 251 females.58 A case series of four Black female patients with truncal acne also showed the effectiveness of combination therapy azelaic acid 15% foam and tretinoin 0.05% lotion.59
Dapsone
Dapsone (4,4'-diaminodiphenylsulfone) has numerous mechanisms of action.60 It exhibits antimicrobial effects due to its ability to inhibit the synthesis of dihydrofolic acid. It is also antiinflammatory through: (1) inhibition of reactive oxygen species production, (2) attenuation of the effect of eosinophil peroxidase on mast cells, and (3) down-regulation of neutrophil-mediated inflammatory responses. It has been approved in both 5% and 7.5% gel formulations for treating acne vulgaris.61-62
Only 1 study has been conducted assessing the efficacy of dapsone specifically for truncal acne. Del Rosso et al performed an open-label study of dapsone 7.5% gel once daily over 16 weeks in 20 subjects with moderate or severe truncal acne aged 12 years or older.63 By week 16, 45% of subjects achieved the primary endpoint of a ≥ 2-grade improvement on IGA with a rating of clear or almost clear. There were also 74%, 69%, and 42% reductions in inflammatory, non-inflammatory, and total lesions, respectively.
Anti-Androgenic Therapies
Another therapeutic strategy for acne is to target the hormonal aspect. Acne is androgen-dependent, and anti-androgen therapies provide benefits. Oral contraceptives (OCPs) provide anti-androgen activity via two major mechanisms: (1) the estrogen component, which stimulates the synthesis of sex hormone binding globulin (SHBG) that in turn reduces the amount of biological active androgens, and (2) the progestin component, which blocks 5-alpha reductase activity to reduce the conversion of testosterone to dihydrotestosterone (DHT).64,52 Only 1 study to date has assessed the use of OCPs in truncal acne.65,53 In this randomized double-blind trial, female patients aged 18 to 45 years old with moderate truncal acne were treated with 3 mg drospirenone / 0.02 mg ethinyl estradiol or placebo over 24 weeks. The OCP group achieved an IGA success rate of 53.3% whereas the placebo group achieved 20%. Spironolactone also increases the synthesis of SHBG and exerts a beneficial anti-androgenic effect on acne. One retrospective study utilizing electronic medical records in a cohort of 110 patients revealed an improvement in chest and back acne by 75.9% and 77.6%, respectively.66,54 A more recent retrospective study of 403 adult women treated for acne with spironolactone also revealed an improvement in chest and back acne by 84.0% and 80.2%, respectively.67,55
Clascoterone is a recently discovered androgen receptor inhibitor that acts against the androgenic component of acne. Its formulation as a topical cream has allowed males to utilize antiandrogen therapy with a significantly lesser concern for systemic off-target effects such as feminization or erectile dysfunction. Clascoterone 1% cream is the first topical androgen receptor inhibitor to be approved for clinical use, and it is currently approved for treatment of acne vulgaris in patients 12 years of age or older.68-69 Two concurrent randomized, vehicle-controlled, double-blind, phase 3 studies (CB-03-01/25 and CB-03-01/26) containing a total of 1,440 subjects between the ages of 9 and 58 were conducted over 12 weeks with treatment success defined as IGA score of 0 (clear) or 1 (almost clear) on IGA and ≥2-grade improvement. Treatment with clascoterone 1% cream applied twice daily had statistically significant improvement compared to vehicle with 57% and 69% achieving treatment success in CB-03-01/25 and CB-03-01/26, respectively. Change from baseline in noninflammatory and inflammatory lesion counts at week 12 were also statistically significantly greater in the clascoterone treatment group with reductions of 30.6% and 29.3%, respectively in noninflammatory lesion counts and 44.8% and 46.9%, respectively, in inflammatory lesion counts. An open-label safety study of the patients who underwent the phase 3 trials for facial acne further demonstrated benefit for truncal acne.70
Sarecycline
Sarecycline is a novel tetracycline that was created specifically for the treatment of acne with a narrow spectrum targeting C. acnes over normal human intestinal microflora.71-72 It is also the only oral tetracycline-class drug with reported truncal efficacy data.73-74 Two concurrent double-blind, randomized phase 3 trials (SC1401 and SC1402) have been conducted in subjects between the ages of 9 and 45.73 IGA scores were used to assess acne severity on the back and chest. A total of 2,002 subjects completed the study. Efficacy was determined as the percentage of patients with a ≥2-point decrease and a rating of clear or almost clear on IGA at week 12. With regard to the back, subjects who received oral sarecycline at a dose of 1.5 mg/kg/day had 32.9% and 33.2% efficacy rate compared to 17.1% and 25.7%
Azelaic Acid
Azelaic acid is a dicarboxylic acid that exhibits anti-inflammatory, anti-infective and skin lightening properties.56 Three studies have assessed azelaic acid foam and cream for truncal acne. Hoffman et al performed a 16-week open-label study utilizing azelaic acid 15% foam in 18 patients and found that 44% achieved a rating of clear or almost clear.57 Kainz et al also found improvement with azelaic acid 20% cream in a 12-week non-interventional study of 251 females.58 A case series of four Black female patients with truncal acne also showed the effectiveness of combination therapy azelaic acid 15% foam and tretinoin 0.05% lotion.59
Dapsone
Dapsone (4,4'-diaminodiphenylsulfone) has numerous mechanisms of action.60 It exhibits antimicrobial effects due to its ability to inhibit the synthesis of dihydrofolic acid. It is also antiinflammatory through: (1) inhibition of reactive oxygen species production, (2) attenuation of the effect of eosinophil peroxidase on mast cells, and (3) down-regulation of neutrophil-mediated inflammatory responses. It has been approved in both 5% and 7.5% gel formulations for treating acne vulgaris.61-62
Only 1 study has been conducted assessing the efficacy of dapsone specifically for truncal acne. Del Rosso et al performed an open-label study of dapsone 7.5% gel once daily over 16 weeks in 20 subjects with moderate or severe truncal acne aged 12 years or older.63 By week 16, 45% of subjects achieved the primary endpoint of a ≥ 2-grade improvement on IGA with a rating of clear or almost clear. There were also 74%, 69%, and 42% reductions in inflammatory, non-inflammatory, and total lesions, respectively.
Anti-Androgenic Therapies
Another therapeutic strategy for acne is to target the hormonal aspect. Acne is androgen-dependent, and anti-androgen therapies provide benefits. Oral contraceptives (OCPs) provide anti-androgen activity via two major mechanisms: (1) the estrogen component, which stimulates the synthesis of sex hormone binding globulin (SHBG) that in turn reduces the amount of biological active androgens, and (2) the progestin component, which blocks 5-alpha reductase activity to reduce the conversion of testosterone to dihydrotestosterone (DHT).64,52 Only 1 study to date has assessed the use of OCPs in truncal acne.65,53 In this randomized double-blind trial, female patients aged 18 to 45 years old with moderate truncal acne were treated with 3 mg drospirenone / 0.02 mg ethinyl estradiol or placebo over 24 weeks. The OCP group achieved an IGA success rate of 53.3% whereas the placebo group achieved 20%. Spironolactone also increases the synthesis of SHBG and exerts a beneficial anti-androgenic effect on acne. One retrospective study utilizing electronic medical records in a cohort of 110 patients revealed an improvement in chest and back acne by 75.9% and 77.6%, respectively.66,54 A more recent retrospective study of 403 adult women treated for acne with spironolactone also revealed an improvement in chest and back acne by 84.0% and 80.2%, respectively.67,55
Clascoterone is a recently discovered androgen receptor inhibitor that acts against the androgenic component of acne. Its formulation as a topical cream has allowed males to utilize antiandrogen therapy with a significantly lesser concern for systemic off-target effects such as feminization or erectile dysfunction. Clascoterone 1% cream is the first topical androgen receptor inhibitor to be approved for clinical use, and it is currently approved for treatment of acne vulgaris in patients 12 years of age or older.68-69 Two concurrent randomized, vehicle-controlled, double-blind, phase 3 studies (CB-03-01/25 and CB-03-01/26) containing a total of 1,440 subjects between the ages of 9 and 58 were conducted over 12 weeks with treatment success defined as IGA score of 0 (clear) or 1 (almost clear) on IGA and ≥2-grade improvement. Treatment with clascoterone 1% cream applied twice daily had statistically significant improvement compared to vehicle with 57% and 69% achieving treatment success in CB-03-01/25 and CB-03-01/26, respectively. Change from baseline in noninflammatory and inflammatory lesion counts at week 12 were also statistically significantly greater in the clascoterone treatment group with reductions of 30.6% and 29.3%, respectively in noninflammatory lesion counts and 44.8% and 46.9%, respectively, in inflammatory lesion counts. An open-label safety study of the patients who underwent the phase 3 trials for facial acne further demonstrated benefit for truncal acne.70
Sarecycline
Sarecycline is a novel tetracycline that was created specifically for the treatment of acne with a narrow spectrum targeting C. acnes over normal human intestinal microflora.71-72 It is also the only oral tetracycline-class drug with reported truncal efficacy data.73-74 Two concurrent double-blind, randomized phase 3 trials (SC1401 and SC1402) have been conducted in subjects between the ages of 9 and 45.73 IGA scores were used to assess acne severity on the back and chest. A total of 2,002 subjects completed the study. Efficacy was determined as the percentage of patients with a ≥2-point decrease and a rating of clear or almost clear on IGA at week 12. With regard to the back, subjects who received oral sarecycline at a dose of 1.5 mg/kg/day had 32.9% and 33.2% efficacy rate compared to 17.1% and 25.7%
