UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Department of Neurology, University of California, San Diego, La Jolla, CA.
Ann Neurol. 2020 Jul;88(1):42-55. doi: 10.1002/ana.25737. Epub 2020 May 14.
To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).
This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile.
A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29-0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14-0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36-0.72, p < 0.001) and gadolinium-enhancing lesions (HR = 0.38, 95% CI = 0.23-0.63, p < 0.001) than those on injectables.
Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.
评估新型疾病修正治疗（DMT）与注射用 DMT 初始治疗在儿科多发性硬化（MS）和临床孤立综合征（CIS）患者疾病活动中的真实世界疗效。
本研究是在美国儿科 MS 中心网络的 12 家诊所对 MS/CIS 患儿进行的队列研究，这些患儿接受了新型（芬戈莫德、二甲基富马酸、特立氟胺、那他珠单抗、利妥昔单抗、奥瑞珠单抗）或注射用（干扰素-β、聚乙二醇干扰素β-1a）DMT 的初始治疗。计算了倾向评分（PS），包括预先确定的混杂因素。采用负二项回归模型对初始 DMT 时的复发率进行建模，调整 PS 五分位数。采用中点生存分析对脑磁共振成像上新出现或扩大的 T2 高信号和钆增强病变的时间进行建模，调整 PS 五分位数。
共有 741 名患儿在 18 岁之前开始治疗，其中 197 名患儿接受了新型 DMT 治疗，544 名患儿接受了注射用 DMT 治疗。使用新型 DMT 治疗的患儿年龄更大（15.2 岁 vs. 注射用组 14.4 岁，p = 0.001），且不太可能出现单灶性表现。在 PS 五分位数调整分析中，新型 DMT 组的复发率低于注射用组（比率比 = 0.45，95%置信区间（CI）为 0.29-0.70，p<0.001；差异率 = 0.27，95%CI = 0.14-0.40，p = 0.004）。为预防 1 例复发，使用新型而非注射用 DMT 治疗 3.7 人年。与注射用组相比，使用新型 DMT 治疗的患儿新出现或扩大的 T2（风险比[HR] = 0.51，95%CI = 0.36-0.72，p<0.001）和钆增强病变（HR = 0.38，95%CI = 0.23-0.63，p<0.001）的发生率更低。
与注射用 DMT 相比，儿科 MS/CIS 患儿初始使用新型 DMT 治疗可更好地控制疾病活动，支持新型疗法的有效性更高。需要长期的新型 DMT 安全性数据。
