Complejo Hospitalario Universitario de A Coruña, Spain.
Complejo Hospitalario Universitario de Vigo, Spain.
Mult Scler Relat Disord. 2023 Jul;75:104762. doi: 10.1016/j.msard.2023.104762. Epub 2023 May 13.
Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed.
A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded.
A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients.
Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.
阿仑单抗是一种治疗复发缓解型多发性硬化症（RRMS）的高效药物，但近年来，由于描述了 CARE-MS I 和 CARE-MS II 三期研究以及 TOPAZ 扩展研究中未登记的新型严重副作用，出现了与安全性相关的担忧。关于阿仑单抗在真实临床实践中的使用的数据有限，主要基于样本量较小的回顾性研究。因此，需要更多关于阿仑单抗在此背景下的有效性和安全性的信息。
进行了一项多中心观察性前瞻性研究，以调查阿仑单抗在真实环境中的疗效和安全性。主要终点是年化复发率（ARR）的变化，以及残疾程度的变化，用 EDSS 评分来衡量。次要终点是确认 6 个月残疾改善和恶化的累积概率。残疾恶化和残疾改善分别被认为是 EDSS 评分增加或减少 1 分（如果基线 EDSS 评分<5.0），或增加或减少 0.5 分（如果基线 EDSS 评分≥5.5），并在 6 个月内得到确认。其他次要终点是达到 NEDA-3 状态（无临床复发、残疾 EDSS 进展以及 MRI 疾病活动，表现为新/扩大的 T2 病变或钆增强 T1 病变）的患者比例。还记录了不良事件。
共纳入 195 例开始接受阿仑单抗治疗的 RRMS 患者（70%为女性）。平均随访时间为 2.38 年。阿仑单抗显著降低了年化复发率，在 12、24 和 36 个月的随访中，风险分别降低了 86%、83.5%和 84%（Friedman 检验，所有比较的 p 值均<0.05）。阿仑单抗还显著降低了 EDSS 评分，在开始阿仑单抗治疗后的 1 年和 2 年（Friedman 检验，p 值均<0.001）。大多数患者在 1、2 和 3 年的随访中表现出确认的 6 个月稳定或残疾改善（分别为 92%、82%和 79%）。在 12、24 和 36 个月时，保留 NEDA-3 状态的患者比例分别为 61%、49%和 42%。与实现 NEDA-3 状态的可能性较低相关的基线特征包括年龄较小、女性、高 ARR、先前治疗次数较多以及从二线治疗转换。输液相关反应是观察到的最常见的不良事件。最常见的感染是尿路感染（50%）和上呼吸道感染（19%），在 3 年的随访中。继发性甲状腺自身免疫在 18.5%的患者中发展。
阿仑单抗在真实临床实践中已证明具有控制多发性硬化症活动的高度有效性，且未观察到意外的不良事件。
