ImportanceIncreasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.ObjectiveTo investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.Design, Setting, and ParticipantsThis multicenter, rater-blinded, noninferiority randomized clinical trial was conducted between July 1, 2020, and March 20, 2023, at 14 Dutch centers. Data analysis was performed between July 2023 and January 2024. Key inclusion criteria were relapse-onset MS, aged 18 years or older, without relapses, and without substantial magnetic resonance imaging (MRI) activity in the previous 5 years under first-line DMT. Participants were randomized 1:1 to discontinue or continue first-line DMT.InterventionDiscontinuation of first-line DMT.Main Outcome and MeasureThe primary outcome was significant inflammatory disease activity, defined as relapse and/or 3 or more new T2 lesions or 2 or more contrast-enhancing lesions on brain MRI.ResultsOf 163 potentially eligible participants, 89 participants were included in the trial at the moment of early termination. Forty-four participants (49.4%) were assigned to the continue group and 45 participants (50.6%) were assigned to the discontinue group. Median (IQR) age was 54.0 (49.0-59.0) years, and 60 participants (67.4%) were female. Two participants in the continue group were lost to follow-up. After a median (IQR) follow-up time of 15.3 (11.4-23.9) months, the trial was prematurely terminated because of inflammatory disease activity recurrence above the predefined limit. In total, 8 of 45 participants in the discontinue group (17.8%) vs 0 of 44 participants in the continue group reached the primary end point and had recurrent, mostly radiological inflammation. Two of these 8 participants had a clinical relapse. Median (IQR) time to disease activity was 12.0 (6.0-12.0) months.Conclusions and RelevanceIn this randomized clinical trial, even in patients with long-term MS stable for over 5 years, first-line DMT discontinuation can lead to recurrence of inflammatory disease activity. Although this study cohort was relatively small, the recurrence of inflammation in the discontinue group was significantly higher than in the continue group and also higher than in the previously published DISCOMS trial, which only included individuals aged 55 years or older. This study provides additional data, especially in a younger population and including longitudinal biomarker measurements, for informed decision-making in cases when treatment discontinuation is considered.Trial RegistrationClinicalTrials.gov Identifier: NCT04260711

中文翻译：

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停止稳定型多发性硬化症患者的一线疾病修正治疗


重要性越来越多的多发性硬化症 （MS） 患者使用疾病缓解疗法 （DMT）。鉴于免疫调节治疗的患者负担、成本和潜在不良反应，在服用此类药物期间疾病长期稳定为考虑停用 DMT 提供了理由。目的探讨长期稳定 MS.Design 患者是否可以安全地停止一线 DMT，环境和参与者这项多中心、评分者盲法、非劣效性随机临床试验于 2020 年 7 月 1 日至 2023 年 3 月 20 日在 14 个荷兰中心进行。数据分析于 2023 年 7 月至 2024 年 1 月期间进行。关键纳入标准是复发性 MS，年龄在 18 岁或以上，没有复发，并且在一线 DMT 下的过去 5 年内没有实质性的磁共振成像 （MRI） 活动。参与者以 1：1 的比例随机分配以停止或继续一线 DMT。干预停止一线 DMT。主要结局和测量主要结局是显著的炎症性疾病活动，定义为复发和/或 3 个或更多新的 T2 病灶或 2 个或更多脑部 MRI 造影剂增强病灶。结果在 163 名可能符合条件的参与者中，89 名参与者在提前终止时被纳入试验。44 名参与者 （49.4%） 被分配到继续组，45 名参与者 （50.6%） 被分配到停药组。中位 （IQR） 年龄为 54.0 （49.0-59.0） 岁，60 名参与者 （67.4%） 为女性。continue 组中的 2 名参与者失访。在中位 （IQR） 随访时间为 15.3 （11.4-23.9） 个月后，由于炎症性疾病活动复发超过预定限度，该试验提前终止。 总的来说，停药组的 45 名参与者中有 8 名 （17.8%） 与继续组的 44 名参与者中有 0 名到达了主要终点，并且出现了复发性炎症，主要是放射学炎症。这 8 名参与者中有 2 名出现临床复发。疾病活动的中位 （IQR） 时间为 12.0 （6.0-12.0） 个月。结论和相关性在这项随机临床试验中，即使在长期稳定 MS 超过 5 年的患者中，一线 DMT 停用也可能导致炎症性疾病活动的复发。虽然这个研究队列相对较小，但停药组的炎症复发率明显高于继续组，也高于之前发表的 DISCOMS 试验，该试验仅包括 55 岁或以上的个体。本研究提供了额外的数据，尤其是在年轻人群中，包括纵向生物标志物测量，以便在考虑停止治疗的情况下做出明智的决策。试验注册临床试验。gov 标识符： NCT04260711