Introduction

Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined.

Objective

The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest.

Methods

Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score.

Results

A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤ 38 years (0.64; 0.54–0.76); in those with disease duration ≤ 7 years (0.63; 0.53–0.76); in those with EDSS score < 4 (0.75; 0.64–0.88), < 6 (0.80; 0.70–0.91), and ≥ 6 (0.52; 0.31–0.86); and in patients with pre-baseline relapses (0.74; 0.64–0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10–1.66); those aged > 38 years (1.34; 1.04–1.73); those with disease duration > 7 years (1.33; 1.01–1.74); those with EDSS score < 6 (1.21; 1.01–1.46) and ≥ 6 (1.93; 1.11–3.34); and patients with no new MRI lesion (1.73; 1.19–2.51).

Conclusions

Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity.

中文翻译：

---

复发缓解型多发性硬化症患者中的那他珠单抗与芬戈莫德：来自三个国际队列的亚组分析

介绍

已证明那他珠单抗在降低复发缓解型多发性硬化症 (RRMS) 的疾病活动方面比芬戈莫德更有效。这种关联是否适用于所有患者群体仍有待确定。

客观的

本研究的目的是比较那他珠单抗和芬戈莫德在由基线人口统计学和感兴趣的临床特征定义的 RRMS 亚组中的相对有效性。

方法

在来自三个国际登记处的合并队列中确定了接受那他珠单抗或芬戈莫德治疗的 RRMS 患者。根据患者的性别、年龄、疾病持续时间、扩展残疾状态量表 (EDSS) 评分以及治疗开始前 12 个月的疾病和磁共振成像 (MRI) 活动，对各亚组的疗效结果进行了比较。研究终点是研究治疗期间记​​录的复发次数（用加权负二项式广义线性模型分析）和 6 个月确认的残疾恶化和改善事件（加权 Cox 比例风险模型）。使用基于倾向评分的治疗加权的逆概率对每位患者进行加权。

结果

共纳入 5148 名患者（那他珠单抗 1989；芬戈莫德 3159），基线时平均 ± 标准差年龄为 38 ± 10 岁，大多数 (72%) 为女性。中位治疗随访时间为 25 个月（四分位数 15-41）个月。与芬戈莫德相比，那他珠单抗的复发率更低（发病率比 [IRR]；95% 置信区间 [CI]）（0.76；0.65-0.88）；年龄≤38岁的人（0.64；0.54-0.76）；病程≤7年的患者（0.63；0.53-0.76）；在 EDSS 评分 < 4 (0.75; 0.64–0.88)、< 6 (0.80; 0.70–0.91) 和 ≥ 6 (0.52; 0.31–0.86) 的患者中；以及基线前复发的患者（0.74；0.64-0.86）。在女性中观察到，那他珠单抗与芬戈莫德相比，确认残疾改善的可能性更高（风险比 [HR]；95% CI）（1.36；1.10-1.66）；年龄 > 38 岁 (1.34; 1.04–1.73); 病程>7年者（1.33；1.01-1.74）；EDSS评分<6（1.21；1.01-1.46）和≥6（1.93；1.11-3.34）的人；和没有新的 MRI 病灶的患者 (1.73; 1.19–2.51)。

结论

总体而言，在女性、年轻患者、病程较短的患者和治疗前复发的患者中，那他珠单抗与多发性硬化症复发率低于芬戈莫德相关。它还与大多数患者，尤其是女性和近期没有 MRI 活动的患者从残疾中恢复的机会增加有关。