Hope Neurology MS Center, Knoxville, TN, USA.
MS Center, Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic.
Mult Scler. 2019 Oct;25(12):1605-1617. doi: 10.1177/1352458518796675. Epub 2018 Oct 5.
Reduced MS disease activity with alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a) in core phase 2/3 studies was accompanied by increased incidence of infections that were mainly nonserious and responsive to treatment. Alemtuzumab efficacy was durable over 6 years.
To evaluate infections over 6 years in alemtuzumab-treated patients.
Three randomized trials (CAMMS223, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I, and CARE-MS II) compared two courses of alemtuzumab 12 mg with SC IFNB-1a 44 μg in patients with active relapsing-remitting MS. An extension study (CAMMS03409) provided further evaluation and as-needed alemtuzumab retreatment.
Infections occurred more frequently with alemtuzumab 12 mg than SC IFNB-1a during Years 1 (58.7% vs 41.3%) and 2 (52.6% vs 37.7%), but declined for alemtuzumab-treated patients in Years 3 (46.6%), 4 (42.8%), 5 (40.9%), and 6 (38.1%). Serious infections were uncommon (1.0%-1.9% per year). Infections were predominantly (>95%) mild to moderate and included upper respiratory tract infections, urinary tract infections, and mucocutaneous herpetic infections. Prophylactic acyclovir reduced herpetic infections. Lymphocyte counts after alemtuzumab therapy did not predict infection risk.
Infections with alemtuzumab were mostly mild to moderate and decreased over time, consistent with preservation of components of protective immunity.
在核心的 2/3 期研究中，与皮下注射干扰素β-1a（SC IFNB-1a）相比，阿仑单抗可降低多发性硬化症（MS）的疾病活动度，同时增加感染的发生率，这些感染主要为非严重感染，且对治疗有反应。阿仑单抗的疗效在 6 年以上持久。
评估阿仑单抗治疗患者 6 年以上的感染情况。
三项随机试验（CAMMS223、阿仑单抗与重组干扰素β-1a在多发性硬化症中的疗效比较（CARE-MS）I 期和 CARE-MS II 期）比较了两疗程的阿仑单抗 12mg 与 SC IFNB-1a 44μg 在活跃的复发缓解型 MS 患者中的疗效。一项扩展研究（CAMMS03409）提供了进一步的评估和按需阿仑单抗再治疗。
在第 1 年（58.7%比 41.3%）和第 2 年（52.6%比 37.7%），阿仑单抗 12mg 治疗组的感染发生率高于 SC IFNB-1a 治疗组，但在第 3 年（46.6%）、第 4 年（42.8%）、第 5 年（40.9%）和第 6 年（38.1%），阿仑单抗治疗组的感染发生率下降。严重感染罕见（每年 1.0%-1.9%）。感染主要为（>95%）轻度至中度，包括上呼吸道感染、尿路感染和黏膜皮肤疱疹感染。预防性阿昔洛韦可降低疱疹感染。阿仑单抗治疗后的淋巴细胞计数不能预测感染风险。
阿仑单抗治疗引起的感染多为轻度至中度，且随时间推移而减少，这与保护性免疫成分的保留一致。
