ARTICLE: Oral Tetracyclines and Acne: A Systematic Review for Dermatologists

November 2020 | Volume 19 | Issue 11 | Supplement Individual Articles | s6 | Copyright © November 2020


Published online October 23, 2020

April W. Armstrong MD MPH,a Joshua Hekmatjah BS,b Leon H. Kircik MDc

aDepartment of Dermatology, University of Southern California, Keck School of Medicine, Los Angeles, CA
bWestern Michigan University, Homer Stryker M.D. School of Medicine, Kalamazoo, MI
cIcahn School of Medicine at Mount Sinai, NY; Skin Sciences, PLLC, Louisville, KY

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,