This stable modification at C-7 is thought to contribute to sarecycline’s targeted activity against C. acnes and the 16- to 32-fold decreased activity against the normal human intestinal microflora.10,11 It has shown little or no antimicrobial activity against Gram-negative bacteria commonly found in the human gut, such as Enterobacteriaceae.10 Due to these unique properties of sarecycline, the potential for antibacterial resistance is low.10,12 C. acnes strains displayed a very low propensity for the development of resistance to sarecycline, with spontaneous mutation frequencies being 10−10 at 4–8 × MIC.10,12 Sarecycline also showed low spontaneous mutation frequencies ranging from 10−9 for S. aureus and 10−8 for S. epidermidis at 4- and 8-fold the MIC.10 Sarecycline was approved by the Federal Drug Administration (FDA) in 2018 for the treatment of moderate-to-severe acne in patients 9 years and older.12 It is also the only oral tetracycline-class drug with reported truncal efficacy data.12 Sarecycline is a once daily treatment that can be taken with or without food, and its weight-based dosing is as follows: 60mg (33–54 kg or 73–120 lb), 100mg (55–84 kg or 121–185 lb), and 150mg (85–136 kg or 186–300 lb).12
Among 2,002 moderate-to-severe acne patients who are 9–45 years old in two phase III trials, researchers found that at the week 12 assessment of facial acne, 21.9% and 22.6% of those who received sarecycline 1.5mg/kg daily achieved the outcome of IGA 0 or 1 versus 10.5% and 15.3% of the placebo group (P<0.0001and P=0.0038) for trials SC1401 and SC1402, respectively (Table 1).11 Both trials also demonstrated significant reductions in the mean percentage change in facial inflammatory lesion counts in the sarecycline-group (-51.8% and -49.9%) as compared to placebo (-35.1% and -35.4%) at week 12 (P<0.0001 for trials SC1401and SC1402, respectively) (Table 1).8 Significant reductions in the mean percentage change in inflammatory lesions in sarecycline-treated patients started as early as week 3.8
Sarecycline also had significantly greater mean percentage reductions in non-inflammatory lesions (open and closed comedones) by week 6 in patients with ≥ 10 baseline noninflammatory lesions (post-hoc pooled analysis).13
Based on the truncal data unique to sarecycline, in patients with moderate-to-severe back acne, 32.9% and 33.2% of the sarecycline group achieved IGA 0 or 1 versus 17.1% and 25.7% in the placebo group (P<0.0001 and P<0.05) at week 12, in the two trials, SC1401 and SC1402, respectively (Table 1).8 In patients with moderate-to-severe chest acne, 29.6% and 36.6% of the sarecycline-group achieved IGA 0 or 1 versus 19.6% and 21.6% of the placebo group (P<0.05 and P<0.0001) at week 12, in the two trials SC1401 and SC1402, respectively (Table 1).8
Sarecycline was overall well tolerated. The most common AE was headache (2.7–2.9%).8 Gastrointestinal AE included nausea (1.9–4.6%), vomiting (0.6–2.1%), and diarrhea (1.0–1.2%).8 There were low rates of sunburn (0.6–0.8%), photosensitivity (0.2%), dizziness (0.4–0.6%), vulvovaginal mycotic infection (0.7–1.0%), and vulvovaginal candidiasis (0.3–1.1%) (Table 1).8 A 40-week open-label safety extension study showed similar results, and thus a safety profile was established for up to 12 months.12,14
Doxycycline
Doxycycline is an oral tetracycline composed of four sixcarbon rings, with a hydroxyl-group at C-5 and a methyl-group at C-6.15 Similar to other tetracyclines, doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
Doxycycline also inhibits neutrophil chemotaxis and matrix metalloproteinases.2,3 It is FDA-approved in the adjunctive treatment of severe acne, and dosing ranges between 50–100mg daily or twice daily.16
In a Phase 2 study of 662 moderate-to-severe acne patients, ages 12 years and older, researchers found that at week 16, the mean decrease in inflammatory lesions was 16.1 in those prescribed 40mg [modified-release (MR)] daily versus 12.6 in the placebo group (P=0.006).17 Both the 40mg (MR) group and 100mg group (16.1 and 12.9, respectively) saw comparable decreases in inflammatory lesions at week 12 (P=0.024).17 The 100mg-group and placebo group (12.9 and 12.6, respectively) saw similar decreases in inflammatory lesions at week 12 with no statically significant difference (P=0.595) (Table 1).15 In this trial, the severity of AE were mild or moderate and included headache (6.5%–6.7%), nausea (3.2%–6.4%), and vomiting (6.7%) (Table 1).17
In one study that assessed doxycycline calcium vs placebo for moderate-to-severe acne, gastrointestinal adverse events ranged from 9.4% to 22.9% in the treatment groups and was 9.0% in the placebo group.9
In a retrospective study of 94,487 acne patients, ages 15–35 years old, researchers found that those who received doxycycline (N=15,032) were over 60% more likely to develop new-onset inflammatory bowel disease (IBD) [hazard ratio (HR) 1.63; 95% CI 1.05–2.52] (Table 1).18
Minocycline
Minocycline is an oral tetracycline composed of four six-carbon rings with a dimethylamine group attached at C-7, making minocycline one of the most lipophilic tetracycline agents.15 Similar to other tetracyclines, minocycline inhibits bacterial protein synthesis by impeding the 30S ribosomal subunit and exerts anti-inflammatory properties by inhibiting neutrophil chemotaxis and matrix metalloproteinases.2,3 Minocycline is FDA-approved in the adjunctive treatment of severe acne,
Among 2,002 moderate-to-severe acne patients who are 9–45 years old in two phase III trials, researchers found that at the week 12 assessment of facial acne, 21.9% and 22.6% of those who received sarecycline 1.5mg/kg daily achieved the outcome of IGA 0 or 1 versus 10.5% and 15.3% of the placebo group (P<0.0001and P=0.0038) for trials SC1401 and SC1402, respectively (Table 1).11 Both trials also demonstrated significant reductions in the mean percentage change in facial inflammatory lesion counts in the sarecycline-group (-51.8% and -49.9%) as compared to placebo (-35.1% and -35.4%) at week 12 (P<0.0001 for trials SC1401and SC1402, respectively) (Table 1).8 Significant reductions in the mean percentage change in inflammatory lesions in sarecycline-treated patients started as early as week 3.8
Sarecycline also had significantly greater mean percentage reductions in non-inflammatory lesions (open and closed comedones) by week 6 in patients with ≥ 10 baseline noninflammatory lesions (post-hoc pooled analysis).13
Based on the truncal data unique to sarecycline, in patients with moderate-to-severe back acne, 32.9% and 33.2% of the sarecycline group achieved IGA 0 or 1 versus 17.1% and 25.7% in the placebo group (P<0.0001 and P<0.05) at week 12, in the two trials, SC1401 and SC1402, respectively (Table 1).8 In patients with moderate-to-severe chest acne, 29.6% and 36.6% of the sarecycline-group achieved IGA 0 or 1 versus 19.6% and 21.6% of the placebo group (P<0.05 and P<0.0001) at week 12, in the two trials SC1401 and SC1402, respectively (Table 1).8
Sarecycline was overall well tolerated. The most common AE was headache (2.7–2.9%).8 Gastrointestinal AE included nausea (1.9–4.6%), vomiting (0.6–2.1%), and diarrhea (1.0–1.2%).8 There were low rates of sunburn (0.6–0.8%), photosensitivity (0.2%), dizziness (0.4–0.6%), vulvovaginal mycotic infection (0.7–1.0%), and vulvovaginal candidiasis (0.3–1.1%) (Table 1).8 A 40-week open-label safety extension study showed similar results, and thus a safety profile was established for up to 12 months.12,14
Doxycycline
Doxycycline is an oral tetracycline composed of four sixcarbon rings, with a hydroxyl-group at C-5 and a methyl-group at C-6.15 Similar to other tetracyclines, doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
Doxycycline also inhibits neutrophil chemotaxis and matrix metalloproteinases.2,3 It is FDA-approved in the adjunctive treatment of severe acne, and dosing ranges between 50–100mg daily or twice daily.16
In a Phase 2 study of 662 moderate-to-severe acne patients, ages 12 years and older, researchers found that at week 16, the mean decrease in inflammatory lesions was 16.1 in those prescribed 40mg [modified-release (MR)] daily versus 12.6 in the placebo group (P=0.006).17 Both the 40mg (MR) group and 100mg group (16.1 and 12.9, respectively) saw comparable decreases in inflammatory lesions at week 12 (P=0.024).17 The 100mg-group and placebo group (12.9 and 12.6, respectively) saw similar decreases in inflammatory lesions at week 12 with no statically significant difference (P=0.595) (Table 1).15 In this trial, the severity of AE were mild or moderate and included headache (6.5%–6.7%), nausea (3.2%–6.4%), and vomiting (6.7%) (Table 1).17
In one study that assessed doxycycline calcium vs placebo for moderate-to-severe acne, gastrointestinal adverse events ranged from 9.4% to 22.9% in the treatment groups and was 9.0% in the placebo group.9
In a retrospective study of 94,487 acne patients, ages 15–35 years old, researchers found that those who received doxycycline (N=15,032) were over 60% more likely to develop new-onset inflammatory bowel disease (IBD) [hazard ratio (HR) 1.63; 95% CI 1.05–2.52] (Table 1).18
Minocycline
Minocycline is an oral tetracycline composed of four six-carbon rings with a dimethylamine group attached at C-7, making minocycline one of the most lipophilic tetracycline agents.15 Similar to other tetracyclines, minocycline inhibits bacterial protein synthesis by impeding the 30S ribosomal subunit and exerts anti-inflammatory properties by inhibiting neutrophil chemotaxis and matrix metalloproteinases.2,3 Minocycline is FDA-approved in the adjunctive treatment of severe acne,