Background

Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use.

Objective

The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug.

Methods

A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart.

Results

ARR decreased from 1.9 (95% confidence interval 1.60–2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17–0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13–0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18–0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported.

Conclusions

This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

中文翻译：

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阿仑单抗治疗复发缓解型多发性硬化症疗效的真实世界回顾性分析：LEMCAM 研究

背景

阿仑单抗（Alemtuzumab）是一种被批准用于治疗复发缓解型多发性硬化症（RRMS）的高效疗法。尽管临床试验和观察性研究在显示其功效和可管理的安全性方面是一致的，但仍需要在临床实践条件下进行进一步的研究以进一步支持其临床使用。

客观的

这项观察性回顾性研究的目的是评估阿仑单抗的有效性和安全性，以补充该药物当前的真实世界证据。

方法

在西班牙的五个中心对 2014 年至 2020 年间接受阿仑单抗治疗的 115 名成年 RRMS 患者进行了回顾性随访。分析包括年复发率 (ARR)、6 个月确认的残疾恶化 (CDW)、6 个月确认的残疾改善 (CDI)、放射活性、无疾病活动证据 (NEDA-3) 和安全信号。考虑到参与者的随访时间不同，ARR 采用人年法计算。CDI 的定义是，在相隔 6 个月确认的基线 EDSS 评分≥ 2.0 的患者中，评估的扩展残疾状态量表 (EDSS) 评分下降 ≥ 1.0 分。CDW被定义为基线EDSS评分≥1.0（如果基线EDSS = 0则≥1.5）的患者评估的EDSS评分增加≥1.0分，间隔6个月确认。

结果

ARR 从阿仑单抗开始前一年的 1.9（95% 置信区间 1.60–2.33）下降至治疗 1 年后的 0.28（0.17–0.37）（降低 87%），第二年后下降至 0.22（0.13–0.35） 。在整个随访期间，ARR 为 0.24 (0.18–0.30)。在第 1 年，75% 的患者没有表现出磁共振成像 (MRI) 活动迹象，第 5 年则为 70%。1% 的患者在第 1 年经历了 6 个月的 CDW，第 2 年为 2.6%，第 3 年为 7.4% ，并且没有患者超过第 4 年和第 5 年。共有 7.7% 的患者在第 1 年达到 6 个月 CDI，第 2 年达到 3.6%，并在第 3 年和第 4 年维持该水平。大多数患者达到年度 NEDA-3：年1、72%；第二年，79%；第三年，80%；第四年，89%；第 5 年，75%。95% 的患者观察到输液相关反应，74% 的患者观察到感染。30% 的患者出现甲状腺疾病，只有 3 名患者出现免疫性血小板减少症。尚未报告进行性多灶性白质脑病病例。

结论

这项研究表明，阿仑单抗在现实临床实践中降低了复发率和残疾恶化，随着时间的推移，许多患者达到并维持了 NEDA-3。阿仑单抗的安全性与之前的研究结果一致，没有观察到新的或意外的安全信号。由于这是一项观察性和回顾性研究，因此在解释结果时应考虑到无法全面提供所有患者的所有变量的主要限制。