Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA.
Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA.
Mult Scler Relat Disord. 2019 Oct;35:119-127. doi: 10.1016/j.msard.2019.07.021. Epub 2019 Jul 25.
Disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) have been shown to reduce relapses and new MRI lesions. However, few studies have assessed the impact of discontinuing DMT after a period of disease inactivity.
To investigate the impact of DMT discontinuation on clinical and radiological outcomes in RRMS patients.
69 RRMS patients who discontinued DMT after a period of disease inactivity were identified from the Comprehensive Longitudinal Investigation of MS study at the Brigham and Women's Hospital, based on the following inclusion criteria: age 18 or older; treated with DMT ≥2 years; no clinical and radiological relapse ≥2 years until the discontinuation; not restarting DMT for ≥6 months after discontinuation. Patients matched by age, gender, treatment, treatment duration, disease duration and Expanded Disability Status Scale score who remained on DMT were identified. Univariate and multivariable Cox proportional hazard models with robust standard errors to account for the paired data were used to test the differences based on DMT discontinuation with the outcome measures: time to clinical relapse, MRI event, disability progression, and disease activity (either clinical relapse or MRI event).
Based on the 69 pairs of patients, discontinuation was not associated with time to clinical relapse (HR = 0.87, 95% CI = 0.44-1.72, p = 0.69), MRI event (HR = 0.95, 95% CI = 0.57 to 1.59, p = 0.84), disability progression (HR = 1.24, 95% CI = 0.61 to 2.53, p = 0.55) and disease activity (HR = 0.89, 95% CI = 0.56 to 1.42, p = 0.62). When we performed subgroup analysis to compare the impact of DMT discontinuation between older (age > 45) and younger (age ≤ 45) patients, we found a significant difference in the association between young and old for time to MRI event (p = 0.012) and time to new disease activity (p = 0.0005).
This study found that patients who discontinued treatment after a period of disease inactivity had a similar time to next event compared to subjects who remained on first-generation DMTs. In our cohort, we found that discontinuation after age 45 was associated with a stable disease course, while patients younger than age 45 who discontinued treatment were more likely to experience a new clinical relapse or MRI event.
对于复发缓解型多发性硬化症（RRMS）患者，疾病修正治疗（DMT）已被证明可减少复发和新的 MRI 病变。然而，很少有研究评估在疾病静止期后停止 DMT 的影响。
探讨 RRMS 患者停止 DMT 对临床和影像学结果的影响。
本研究基于以下纳入标准，从布里格姆妇女医院的综合多发性硬化纵向研究中确定了 69 名在疾病静止期后停止 DMT 的 RRMS 患者：年龄 18 岁或以上；接受 DMT 治疗≥2 年；疾病静止期≥2 年，无临床和影像学复发；停止治疗后≥6 个月未重新开始 DMT。根据年龄、性别、治疗、治疗持续时间、疾病持续时间和扩展残疾状况量表评分匹配仍在接受 DMT 治疗的患者。使用具有稳健标准误差的单变量和多变量 Cox 比例风险模型来检验基于 DMT 停药的差异，结果衡量指标包括临床复发、MRI 事件、残疾进展和疾病活动（临床复发或 MRI 事件）。
基于 69 对患者，停药与临床复发时间（HR=0.87，95%CI=0.44-1.72，p=0.69）、MRI 事件（HR=0.95，95%CI=0.57 至 1.59，p=0.84）、残疾进展（HR=1.24，95%CI=0.61 至 2.53，p=0.55）和疾病活动（HR=0.89，95%CI=0.56 至 1.42，p=0.62）无关。当我们进行亚组分析比较年龄较大（年龄>45 岁）和年龄较小（年龄≤45 岁）患者之间停止 DMT 的影响时，我们发现年轻和年老患者之间在 MRI 事件时间（p=0.012）和新疾病活动时间（p=0.0005）方面的关联存在显著差异。
本研究发现，在疾病静止期后停止治疗的患者与继续使用第一代 DMT 的患者相比，下一次事件的时间相似。在我们的队列中，我们发现 45 岁以后停药与稳定的疾病过程相关，而年龄小于 45 岁停止治疗的患者更有可能出现新的临床复发或 MRI 事件。
