Leyden James J, Sniukiene Vilma, Berk David R, Kaoukhov Alexandre
J Drugs Dermatol. 2018 Mar 1;17(3):333-338.
There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris.
In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations.
Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred.
Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.
J Drugs Dermatol. 2018;17(3):333-338.
.需要研发新的用于治疗痤疮的口服抗生素，使其具有更好的安全性和针对性抗菌谱。丝柔四环素是一种新型四环素类抗生素，专为治疗痤疮设计，与现有的四环素类药物相比，其抗菌谱较窄，对肠道革兰氏阴性菌的活性较低。这项2期研究评估了三种剂量的丝柔四环素治疗中度至重度寻常性面部痤疮的疗效和安全性。
在这项多中心、双盲、安慰剂对照研究中，年龄在12至45岁之间的患者被随机分为每日一次服用0.75mg/kg、1.5mg/kg、3.0mg/kg的丝柔四环素组或安慰剂组。疗效分析包括第12周时炎症性和非炎症性皮损计数相对于基线的变化，采用协方差分析进行组间比较。安全性评估包括不良事件（AE）、临床实验室检查、生命体征、心电图和体格检查。
总体而言，285名随机分组的患者接受了至少一剂研究药物。在第12周时，丝柔四环素1.5mg/kg组和3.0mg/kg组的炎症性皮损相对于基线显著减少（分别为52.7%和51.8%），而安慰剂组为38.3%（分别为P=0.02和P=0.03）。丝柔四环素安全且耐受性良好，丝柔四环素组和安慰剂组的胃肠道不良事件发生率相似。合并丝柔四环素组时，眩晕和光敏性不良事件的发生率低于1%；未发生外阴阴道念珠菌病不良事件。因不良事件导致的停药率较低。未发生严重不良事件。
与安慰剂相比，每日一次服用1.5mg/kg的丝柔四环素可显著减少炎症性皮损，且安全且耐受性良好，不良事件发生率低，包括胃肠道不良事件。3.0mg/kg的丝柔四环素与1.5mg/kg相比并未带来额外疗效。丝柔四环素可能是一种治疗中度至重度痤疮患者的新型每日一次用药。与其他四环素类药物相比，其抗菌谱较窄，这可能导致对肠道革兰氏阴性菌的选择性压力较小，从而减少对共生生物的干扰以及抗生素耐药性的潜在风险。
《药物皮肤病学杂志》。2018年；17(3):333 - 338。
