早期强化治疗与逐步升级治疗方法：对复发型多发性硬化症患者残疾状况的十年影响

Early Intensive Versus Escalation Approach: Ten-Year Impact on Disability in Relapsing Multiple Sclerosis.

作者信息

Iaffaldano Pietro, Lucisano Giuseppe, Guerra Tommaso, Caputo Francesca, Simone Marta, Copetti Massimiliano, Paolicelli Damiano, Portaccio Emilio, Patti Francesco, Perini Paola, Brescia Morra Vincenzo, Di Sapio Alessia, Inglese Matilde, Pozzilli Carlo, Lus Giacomo, Salemi Giuseppe, Curti Erica, De Luca Giovanna, Valentino Paola, Cocco Eleonora, Cavalla Paola, Avolio Carlo, Lugaresi Alessandra, Gallo Antonio, Annovazzi Pietro, Rocca Maria A, Chisari Clara Grazia, Filippi Massimo, Amato Maria Pia, Trojano Maria

机构信息

Department of Translational Biomedicines and Neurosciences (DiBraiN), University of Bari "Aldo Moro", Bari, Italy.

CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy.

出版信息

Ann Clin Transl Neurol. 2025 Jul 6. doi: 10.1002/acn3.70131.

DOI:10.1002/acn3.70131

PMID:40619726

Abstract

OBJECTIVE

To evaluate the long-term impact of early intensive treatment (EIT) versus escalation (ESC) strategies using high-efficacy disease-modifying therapies (HE-DMTs) on disability progression in relapsing multiple sclerosis (RMS).

METHODS

This observational study included 4878 RMS patients from the Italian Multiple Sclerosis Register. Eligible participants initiated their first disease-modifying therapy (DMT) within 3 years of disease onset and had ≥ 5 years of follow-up with at least three Expanded Disability Status Scale (EDSS) evaluations. Patients were categorized into the EIT group if they started with HE-DMTs and into the ESC group if HE-DMTs were initiated after ≥ 1 year of moderate-efficacy therapy. Propensity score matching was performed to balance baseline characteristics. Outcomes included disability trajectories assessed using linear mixed models for repeated measures and risks of confirmed disability accrual (CDA), progression independent of relapse activity (PIRA), and relapse-associated worsening (RAW) evaluated using Cox proportional hazards models.

RESULTS

Post-matching analysis of 908 pairs revealed significantly slower disability progression in the EIT group compared to the ESC group. At 10 years, the delta-EDSS difference between groups was -0.63 (95% CI: -0.83 to -0.43; p < 0.0001). ESC was associated with higher risks of CDA (HR 1.36, 95% CI: 1.20-1.54; p < 0.0001), PIRA (HR 1.22, 95% CI: 1.05-1.40; p = 0.0074), and RAW (HR 1.55, 95% CI: 1.17-2.05; p = 0.0021).

INTERPRETATION

EIT significantly reduces long-term disability progression in RMS compared to ESC. These findings underscore the potential of EIT to optimize long-term outcomes in RMS patients.

摘要

目的

评估使用高效疾病修正疗法（HE-DMTs）的早期强化治疗（EIT）与逐步升级治疗（ESC）策略对复发型多发性硬化症（RMS）残疾进展的长期影响。

方法

这项观察性研究纳入了来自意大利多发性硬化症登记处的4878例RMS患者。符合条件的参与者在疾病发作后3年内开始首次疾病修正治疗（DMT），并进行了≥5年的随访，至少有三次扩展残疾状态量表（EDSS）评估。如果患者从HE-DMTs开始治疗，则分为EIT组；如果在使用中等疗效疗法≥1年后开始使用HE-DMTs，则分为ESC组。进行倾向得分匹配以平衡基线特征。结局包括使用重复测量的线性混合模型评估的残疾轨迹，以及使用Cox比例风险模型评估的确诊残疾累积（CDA）、与复发活动无关的进展（PIRA）和复发相关恶化（RAW）风险。

结果

对908对患者进行匹配后分析发现，与ESC组相比，EIT组的残疾进展明显较慢。在10年时，两组之间的EDSS差值为-0.63（95%CI：-0.83至-0.43；p<0.0001）。ESC与更高的CDA风险（HR 1.36，95%CI：1.20-1.54；p<0.0001）、PIRA风险（HR 1.22，95%CI：1.05-1.40；p=0.0074）和RAW风险（HR 1.55，95%CI：1.17-2.05；p=0.0021）相关。