Background Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals. Methods The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID). Results Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI −4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy. Conclusions MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks. Trial registration number [NCT04225312][1]. Data are available upon request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04225312&atom=%2Fjnnp%2F95%2F5%2F392.atom

中文翻译：

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通过治疗药物监测进行那他珠单抗个性化延长间隔给药治疗复发缓解型多发性硬化症 (NEXT-MS) 的前瞻性试验

背景 那他珠单抗的延长间隔给药 (EID) 是优化多发性硬化症 (MS) 治疗的一种有前景的策略。通过治疗药物监测实现个性化 EID 可以进一步延长治疗间隔。方法 NEXT-MS 试验是一项由研究者发起的前瞻性 IV 期非随机研究。接受≥6 次那他珠单抗输注的诊断为复发缓解型多发性硬化症的成人被分为三组：目标药物谷浓度为 10 µg/mL 的个性化 EID (EID10)、目标药物谷浓度为 5 µg 的个性化 EID 探索组/mL (EID5) 和标准给药间隔 (SID) 为 4 周。主要结局是将 EID10 组与 SID (HSID) 历史队列进行比较的放射学疾病活动性（新的/新扩大的 T2 病灶）。结果此处报告了 NEXT-MS 试验第一阶段的结果 (n=376)，该研究将按照修订后的方案继续进行。在EID10组（n=251）中，放射性活动发生率为10.0/1000人年，不劣于HSID组（24.7/1000人年（n=87），发生率差异14.7， 90% CI -4.5 至 34.0）。 EID5 组（n=65）的放射活动发生率为每 1000 人年 10.0 例，SID 组（n=60）为每 1000 人年 47.0 例。 EID 组中血清神经丝光水平没有随时间增加。没有进行性多灶性白质脑病的病例。结论 个性化那他珠单抗 EID 可以充分控制 MS 疾病活动度。将药物谷浓度延长至 5 µg/mL 的间隔可能是延长那他珠单抗治疗间隔 > 6 周的安全目标。试用注册号[NCT04225312][1]。数据可根据要求提供。 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04225312&atom=%2Fjnnp%2F95%2F5%2F392.atom