Inflammation is a backdrop to the commonly cited elements of the pathophysiology of acne: Propionibacterium acnes proliferation, increased sebum production with an increase in circulating androgens, and faulty keratinization.1,2 In fact, research shows that the initiating lesion of acne vulgaris—the microcomedone—is, in essence, an inflammatory lesion.3 This realization has clearly influenced the approach to acne treatment but has not yielded a bevy of new treatments.
A better understanding of acne pathophysiology and the role of inflammation has, however, yielded a better understanding of how existing therapies treat the disease and have led to more comprehensive treatment strategies that are multitargeted. Nonetheless, topical and oral antibiotics remain mainstays of acne therapy, along with topical retinoids and benzoyl peroxide. Current guidelines of care for acne emphasize strategies that reduce dependence on antibiotics and minimize the risk for resistance.4 The therapeutic landscape might at last be shifting, with new chemical entities for acne and several novel formulations in development.
Sarecycline: A Novel Tetracycline
Tetracycline antibiotics have been used to manage acne since the 1950s, but their method of action in the disease has not been fully elucidated.5 In addition to antibiotic effects, tetracyclines have been shown to confer anti-inflammatory properties and other biologic effects.6,7
First-generation tetracycline is broad spectrum. As such, it is associated with increased potential for antibiotic resistance and greater impact on gastrointestinal health. The novel compound sarecycline is a tetracycline with a narrower spectrum of activity compared to other tetracyclines and with reduced activity against enteric gram-negative bacteria8 (Figure 1). Sarecycline recently was approved by the US Food and Drug Administration (FDA) in a once-daily oral formulation for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. Sarecycline is dosed at 1.5 mg/kg daily. The FDA approval marks the first new antibiotic approved for acne in 4 decades.
In 2 phase 3 clinical trials, sarecycline demonstrated efficacy in reducing both inflammatory and noninflammatory lesions.9 At week 12, investigator global assessment (IGA) success (≥2 point reduction in IGA and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% for active treatment (n=483 and n=519), respectively, in the 2 trials compared to 10.5% and 15.3% (n=485 and n=515), respectively, for controls. Sarecycline demonstrated rapid anti-inflammatory effect. Onset of action against inflammatory lesions was notable by week 3. At week 12, inflammatory lesions were reduced in the active treatment arms by 51.8% and 49.9%, respectively, compared to 35.1% and 35.4%, respectively, for controls.9
The most common reported treatment-emergent adverse events (TEAEs) were nausea, nasopharyngitis, headache, and vomiting.9 Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in 1% or fewer of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low.9
Sarecycline also was assessed in the 2 trials for efficacy in the treatment of back and chest acne; in the active treatment group, IGA success was achieved by 29.6% and 36.6%, respectively, compared to 19.6% and 21.6%, respectively, of controls.9