Hersh Carrie M, Harris Haleigh, Conway Devon, Hua Le H
Lou Ruvo Center for Brain Health (CMH, HH, LHH), Cleveland Clinic, Las Vegas, NV; and Mellen Center for Multiple Sclerosis Treatment and Research (DC), Cleveland Clinic, Cleveland, OH.
Neurol Clin Pract. 2020 Dec;10(6):e53-e65. doi: 10.1212/CPJ.0000000000000809.
To assess the real-world comparative effectiveness of switching from natalizumab (NTZ) to a moderate-efficacy (Mod) disease-modifying therapy (DMT) vs high-efficacy therapy (HET) in patients with multiple sclerosis (MS).
Patients discontinuing NTZ at two MS centers (n = 556) who switched to Mod DMT (n = 270) vs HET (n = 130) were assessed using propensity score (PS) weighting. PS model covariates included demographics and baseline clinical and MRI characteristics. All outcomes were reported as Mod DMT vs HET.
Of the patients included in the study, 48.6% switched to Mod DMT (dimethyl fumarate, n = 130; fingolimod, n = 140) vs 23.4% who switched to HET (ocrelizumab, n = 106; rituximab, n = 17; alemtuzumab, n = 7). Within the first 6 months post-NTZ, switchers to Mod DMT experienced comparable relapses (odds ratio [OR] = 1.36, 95% confidence interval [CI] [0.72-1.66], = 0.724), although they had increased MRI activity on treatment (OR = 2.59, 95% CI [1.09-3.57], = 0.037). By 24 months post-NTZ, there was no difference in the annualized relapse rate (OR = 1.44, 95% CI [0.69-1.59], = 0.334) or time to first clinical relapse (HR = 2.12, 95% CI [0.87-5.17], = 0.090), although switchers to Mod DMT had higher gadolinium-enhancing (GdE) lesions (OR = 3.62, 95% CI [1.56-5.21], = 0.005), earlier time to first GdE lesion (HR = 6.67, 95% CI [2.06-9.16], = 0.002), lower proportion with the absence of disease activity (OR = 0.41, 95% CI [0.21-0.71], = 0.004), and higher risk of disability progression on T25FW (OR = 1.83, 95% CI [1.06-3.02], = 0.043) and 9-HPT (OR = 1.81, 95% CI [1.05-3.56], = 0.044).
Patients switching from NTZ to Mod DMT vs HET were at relatively increased risk of disease activity within the first 6 months of NTZ withdrawal that was sustained at 24 months, yielding greater disability progression.
评估多发性硬化症（MS）患者从那他珠单抗（NTZ）转换为中等疗效（Mod）疾病修饰治疗（DMT）与高效治疗（HET）相比在现实世界中的相对有效性。
在两个MS中心停用NTZ的患者（n = 556）中，使用倾向评分（PS）加权评估转换为Mod DMT（n = 270）与HET（n = 130）的患者。PS模型协变量包括人口统计学以及基线临床和MRI特征。所有结果均报告为Mod DMT与HET的比较。
在纳入研究的患者中，48.6%转换为Mod DMT（富马酸二甲酯，n = 130；芬戈莫德，n = 140），而23.4%转换为HET（奥瑞珠单抗，n = 106；利妥昔单抗，n = 17；阿仑单抗，n = 7）。在停用NTZ后的前6个月内，转换为Mod DMT的患者经历了相当的复发（优势比[OR]=1.36，95%置信区间[CI][0.72 - 1.66]，P = 0.724），尽管他们在治疗期间MRI活动增加（OR = 2.59，95%CI[1.09 - 3.57]，P = 0.037）。到停用NTZ后24个月时，年化复发率（OR = 1.44，95%CI[0.69 - 1.59]，P = 0.334）或首次临床复发时间（风险比[HR]=2.12，95%CI[0.87 - 5.17]，P = 0.090）没有差异，尽管转换为Mod DMT的患者钆增强（GdE）病灶更多（OR = 3.62，95%CI[1.56 - 5.21]，P = 0.005），首次GdE病灶出现时间更早（HR = 6.67，95%CI[2.06 - 9.16]，P = 0.002），无疾病活动的比例更低（OR = 0.41，95%CI[0.21 - 0.71]，P = 0.004），并且在T25FW（OR = 1.83，95%CI[1.06 - 3.02]，P = 0.043）和9-HPT（OR = 1.81，95%CI[1.05 - 3.56]，P = 0.044）上残疾进展风险更高。
从NTZ转换为Mod DMT与HET的患者在停用NTZ的前6个月内疾病活动风险相对增加，并持续至24个月，导致更大的残疾进展。
