Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study
Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study
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多发性硬化症高效疗法的时机选择：一项回顾性观察队列研究
DOI：
10.1016/s1474-4422(20)30067-3
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发表时间：
2020-04-01
期刊：
影响因子：
48
通讯作者：
Kalincik, Tomas
中科院分区：
文献类型：
--
作者：
He, Anna;Merkel, Bernd;Kalincik, Tomas
背景：多发性硬化症的高效疗法传统上是在一线疾病修饰疗法治疗失败后使用的。我们假设早期开始高效治疗与减少长期残疾有关，因此我们旨在比较在发病2年内开始高效治疗的患者与发病4-6年后开始高效治疗的患者之间的长期残疾结果。方法在这项回顾性的国际观察性研究中，我们从MSBase注册中心和瑞典MS注册中心获得数据，这些数据前瞻性地收集了多发性硬化症的患者数据，作为常规临床护理的一部分。我们确定了患有复发-缓解型多发性硬化症的成年患者（年龄11 - 8岁），自发病以来至少随访6年，并且在临床发病后0-2年（早期）或4-6年（晚期）开始高效治疗（利妥昔单抗、奥克雷单抗、米托蒽酮、阿仑单抗或那他单抗）。我们使用基于基线临床和人口统计数据计算的倾向得分来匹配早期组和晚期组的患者。主要结局是残疾，在发病后6-10年，用扩展残疾状态评分（EDSS；一个0-10分的有序量表，得分越高表明残疾程度越高）来衡量，用线性混合效应模型进行评估。研究人员在MSBase注册表中确定了6149例接受了高效治疗的患者，数据收集于1975年1月1日至2017年4月13日；在瑞典MS注册表中确定了2626例患者，数据收集于1997年12月10日至2019年9月16日。其中，MS Base注册中心的308名和瑞典MS注册中心的236名符合纳入条件。544例患者中有277例（51%）早期开始治疗，267例（49%）晚期开始治疗。在初步分析中，我们将213例早期治疗组患者与253例晚期治疗组患者进行了配对。基线时，早期组平均EDSS评分为2.2 (SD 1.2)，晚期组平均EDSS评分为2.1 （SD 1.2）。匹配患者的中位随访时间为7.8年（IQR 6）。7 - 8。9)。在发病后的第六年，早期组的平均EDSS评分为2.2 (SD 1.6)，而晚期组的平均EDSS评分为2.9 （SD 1.8）
Background High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.Methods In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS regtstry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ai8 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model.Findings We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1,1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10,1997, and Sept 16,2019. Of whom, 308 in the MS Base registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2.2 (SD 1.2) in the early group and 2.1 (SD 1.2) in the late group. Median follow-up time for matched patients was 7.8 years (IQR 6. 7-8. 9). In the sixth year after disease onset, the mean EDSS score was 2.2 (SD 1.6) in the early group compared with 2.9 (SD 1.8) in the late group (p