Butzkueven Helmut, Kalincik Tomas, Patti Francesco, Slee Mark, Weinstock-Guttman Bianca, Buzzard Katherine, Skibina Olga, Alroughani Raed, Prat Alexandre, Girard Marc, Horakova Dana, Havrdova Eva Kubala, Van der Walt Anneke, Eichau Sara, Hyde Robert, Campbell Nolan, Bodhinathan Karthik, Spelman Tim
Department of Neuroscience, Central Clinical School, Alfred Campus, Monash University, 6/99 Commercial Road, Melbourne, VIC 3004, Australia.
Department of Neurology, Box Hill Hospital, Monash University, Box Hill, VIC, Australia.
Ther Adv Neurol Disord. 2024 Feb 26;17:17562864231221331. doi: 10.1177/17562864231221331. eCollection 2024.
Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance.
Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate).
This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD.
This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW).
After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients ( < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients.
Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.
多发性硬化症（MS）诊断后尽快积极控制病情可能预防不可逆的神经损伤，因此早期启动高效疾病修正治疗（DMT）具有临床意义。
评估接受那他珠单抗或BRACETD治疗（干扰素β、醋酸格拉替雷、特立氟胺或富马酸二甲酯）的MS患者的长期临床结局。
这项回顾性分析利用MSBase的数据创建了一个匹配人群，以便比较一线那他珠单抗与一线BRACETD。
本研究纳入了在MS诊断后1年内开始接受那他珠单抗或BRACETD DMT治疗并持续治疗≥6个月的患者，此后患者可以更换DMT或停止治疗。患者从开始治疗起的最短随访时间为≥60个月。一项亚组分析将那他珠单抗组与BRACETD组中6个月后升级治疗的患者进行了比较。结局包括未调整的年化复发率（ARRs）、首次复发时间、首次确认残疾改善（CDI）时间和首次确认残疾恶化（CDW）时间。
经过1:1倾向评分匹配后，3５５例BRACETD患者与355例那他珠单抗患者匹配。开始使用那他珠单抗的患者在随访期间复发的可能性较小，那他珠单抗患者的ARRs [95%置信区间（CI）]为0.080（0.070-0.092），BRACETD患者为0.191（0.178-0.205）（P＜0.0001）。首次复发时间的Cox回归模型显示那他珠单抗患者复发风险降低[风险比（95%CI）为0.52（0.42-0.65）；P＜0.001]，且首次CDI时间更有利。两组间CDW风险相似。亚组分析显示BRACETD患者复发风险增加，CDW风险也显著更高。
与BRACETD相比，早期启动那他珠单抗在复发结局方面产生了长期益处，无论后续治疗是否升级。
