Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.
Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.
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DOI：
10.1212/wnl.0000000000004354
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发表时间：
2017-09-12
期刊：
影响因子：
9.9
通讯作者：
CARE-MS II and CAMMS03409 Investigators
中科院分区：
文献类型：
--
作者：
Coles AJ;Cohen JA;Fox EJ;Giovannoni G;Hartung HP;Havrdova E;Schippling S;Selmaj KW;Traboulsee A;Compston DAS;Margolin DH;Thangavelu K;Chirieac MC;Jody D;Xenopoulos P;Hogan RJ;Panzara MA;Arnold DL;CARE-MS II and CAMMS03409 Investigators
评估阿仑单抗在活动性复发-缓解型多发性硬化症和对既往治疗反应不足的患者中的5年疗效和安全性。在为期2年的阿仑单抗和瑞比夫在多发性硬化症（CARE-MS） II期疗效比较研究（NCT00548405）中，阿仑单抗治疗的患者接受了2个疗程（基线和12个月后）。患者可以进入延长期（NCT00930553），根据需要对复发或MRI活动进行阿仑单抗再治疗。评估年复发率（ARR）、6个月确认残疾恶化（CDW；≥1分扩展残疾状态量表[EDSS]评分增加[基线EDSS = 0≥1.5]）、6个月确认残疾改善（CDI；≥1分EDSS降低[基线评分≥2.0]）、无疾病活动证据（NEDA）、脑容量损失（BVL）和不良事件（ae）。完成CARE-MS II的大多数阿仑单抗治疗患者（92.9%）进入延长期；59.8%的患者未接受阿仑单抗再治疗。ARR各延长年均较低（3 ~ 5年分别为0.22、0.23、0.18）。通过5年，75.1%的患者没有6个月的CDW；42.9%达到6个月CDI。在第3、4和5年，NEDA的比例分别为52.9%、54.2%和58.2%。在延长期间，年BVL中位数仍然很低（1-5年：- 0.48%,- 0.22%,- 0.10%,- 0.19%,- 0.07%）。扩展组的AE暴露调整发生率低于核心组。甲状腺疾病在第三年达到顶峰，此后逐渐下降。在没有持续治疗的情况下，对先前治疗反应不足的患者，阿仑单抗可提供长达5年的持久疗效。这项研究提供了III级证据，证明阿仑妥珠单抗在5年内有效并减缓脑萎缩。
To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3–5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.