Pasca Matteo, Forci Benedetta, Mariottini Alice, Mechi Claudia, Barilaro Alessandro, Massacesi Luca, Repice Anna Maria
Department of Neurosciences Drugs and Child Health, University of Florence, Florence, Italy.
Department of Neurosciences Drugs and Child Health, University of Florence, Florence, Italy; Deparment of Neurology 2, Careggi University Hospital, Florence, Italy.
Mult Scler Relat Disord. 2021 Jan;47:102591. doi: 10.1016/j.msard.2020.102591. Epub 2020 Oct 21.
The natural history of multiple sclerosis (MS) following discontinuation of a first-line disease-modifying treatment (DMT) in relapsing-remitting (RR-) MS patients is controversial, as few data are available on the risk of disease reactivation. This study aims to investigate the disease course after DMT discontinuation in selected RR-MS patients, exploring potential predictive factors of disease reactivation.
RR-MS patients, aged 18-65, who had discontinued a first-line DMT were selected from 1107 clinical records. Relapses, disability worsening and new brain lesions, before and after DMT interruption, were retrospectively evaluated. Potentially predictive baseline characteristics of disease reactivation were also analysed.
N= 60 patients were included, median age and treatment duration were 47.8 (22.1-64.3) and 7.2 (0.5-17.8) years respectively. Median clinical follow-up after discontinuation was 4.6 (0.5-16.6) years. No disease rebound occurred. Mean annualized disease activity and relapse rate after discontinuation were both lower than during treatment(0.10±0.05 vs 0.15 ±0.05; p=0.017). A NEDA-3 period on treatment ≥5.5 years was associated with a low rate (7.7%) and a low risk of new disease activity (aHR 0.16, CI 0.03-0.78, p=0.024; Cox regression model multivariate analysis). The patients with NEDA-3 period threshold above 5.5 years showed a higher probability of surviving to disease reactivation than others (p=0.014).
In most of the MS patients who showed a long NEDA-3 period while on treatment remission of disease activity persists following first-line DMT discontinuation, suggesting that prolonged suppression of disease activity on treatment can determine long term sustained remission of the disease also in absence of treatment.
复发缓解型（RR-）多发性硬化症（MS）患者停用一线疾病修正治疗（DMT）后的自然病程存在争议，因为关于疾病重新激活风险的数据很少。本研究旨在调查选定的RR-MS患者停用DMT后的病程，探索疾病重新激活的潜在预测因素。
从1107份临床记录中选取年龄在18-65岁之间且已停用一线DMT的RR-MS患者。对DMT中断前后的复发、残疾恶化和新的脑损伤进行回顾性评估。还分析了疾病重新激活的潜在预测基线特征。
纳入60例患者，中位年龄和治疗时间分别为47.8（22.1-64.3）岁和7.2（0.5-17.8）年。停药后的中位临床随访时间为4.6（0.5-16.6）年。未发生疾病反弹。停药后的年均疾病活动度和复发率均低于治疗期间（0.10±0.05对0.15±0.05；p=0.017）。治疗期间NEDA-3期≥5.5年与低发生率（7.7%）和新疾病活动低风险相关（风险比0.16，可信区间0.03-0.78，p=0.024；Cox回归模型多变量分析）。NEDA-3期阈值高于5.5年的患者存活至疾病重新激活的概率高于其他患者（p=0.014）。
在大多数治疗期间显示长NEDA-3期的MS患者中，停用一线DMT后疾病活动缓解持续存在，这表明治疗期间对疾病活动的长期抑制也可在无治疗的情况下决定疾病的长期持续缓解。
