Pfeuffer Steffen, Wolff Stephanie, Aslan Derya, Rolfes Leoni, Korsen Melanie, Pawlitzki Marc, Albrecht Philipp, Havla Joachim, Huttner Hagen B, Kleinschnitz Christoph, Meuth Sven G, Pul Refik, Ruck Tobias
From the Department of Neurology (S.P., S.W., H.B.H.), University Hospital Giessen, Justus-Liebig-University Giessen; Department of Neurology (D.A., C.K., R.P.), University Hospital Essen, University Duisburg-Essen; Department of Neurology (L.R., M.K., M.P., S.G.M., T.R.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (P.A.), Medical Faculty, Heinrich Department of Neurology, Maria-Hilf-Clinic, Mönchengladbach; and Institute of Clinical Neuroimmunology (J.H.), LMU Hospital, Ludwig-Maximilians University Munich, Germany.
Neurology. 2024 Jul 23;103(2):e209574. doi: 10.1212/WNL.0000000000209574. Epub 2024 Jun 13.
Relapse and MRI activity usually decline with aging but are replaced by progression independent of relapse activity (PIRA) in patients with multiple sclerosis (PwMS). However, several older PwMS continue to experience clinical relapses, and the impact on their disease remains undetermined. We aimed to determine the impact of an index relapse on disease outcomes in patients older than 50 years and to identify risk factors of disadvantageous outcomes.
We performed a secondary analysis from 3 prospective cohorts in Germany. We evaluated all PwMS 50 years and older with a relapse ≤60 days before a baseline visit and at least 18 months of follow-up compared with a control cohort of PwMS without a relapse. Patients were stratified according to age ("50-54" vs "55-59" vs "60+") or disease outcomes ("stable" vs "active" vs "progressive," according to the Lublin criteria). We analyzed relapses, MRI activity, relapse-associated worsening, and PIRA. Regression analysis was performed to evaluate the association of specific baseline risk factors and treatment regimen changes with disease outcomes at month 18.
A total of 681 patients were included in the "relapse cohort" (50+: 361; 55+: 220; 60+: 100). The "control cohort" comprised 232 patients (50+: 117; 55+: 71; 60+: 44). Baseline epidemiologic parameters were balanced among cohorts and subgroups. We observed increased abundance of inflammatory activity and relapse-independent disability progression in the "relapse" vs "control" cohort. In the "relapse" cohort, we identified 273 patients as "stable" (59.7%), 114 patients as "active" (24.9%), and 70 patients as "progressive" (15.3%) during follow-up. Cardiovascular risk factors (CVRFs) and older age at baseline were identified as risk factors of progressive, whereas disease-modifying treatment (DMT) administration at baseline favored stable disease. DMT during follow-up was associated with stable over active, but not over progressive disease.
A relapse-suggesting underlying active disease-in PwMS older than 50 years was associated with continued disease activity and increased risk of PIRA. Presence of CVRF and absence of DMT at baseline appeared as risk factors of disadvantageous disease courses. An escalation of DMT switch was associated with stable over active but not progressive disease.
复发和磁共振成像（MRI）活动通常会随着年龄增长而下降，但在多发性硬化症患者（PwMS）中，会被与复发活动无关的疾病进展（PIRA）所取代。然而，一些老年PwMS患者仍会经历临床复发，其对疾病的影响尚不确定。我们旨在确定50岁以上患者首次复发对疾病转归的影响，并识别不良转归的危险因素。
我们对德国3个前瞻性队列进行了二次分析。我们评估了所有年龄在50岁及以上、在基线访视前60天内有复发且随访至少18个月的PwMS患者，并与无复发的PwMS对照队列进行比较。根据年龄（“50 - 54岁” vs “55 - 59岁” vs “60岁及以上”）或疾病转归（根据卢布林标准分为“稳定” vs “活动” vs “进展”）对患者进行分层。我们分析了复发、MRI活动、复发相关的病情恶化和PIRA。进行回归分析以评估特定基线危险因素和治疗方案变化与18个月时疾病转归的关联。
“复发队列”共纳入681例患者（50岁及以上：361例；55岁及以上：220例；60岁及以上：100例）。“对照队列”包括232例患者（50岁及以上：117例；55岁及以上：71例；60岁及以上：44例）。各队列和亚组之间的基线流行病学参数均衡。我们观察到“复发”队列与“对照”队列相比，炎症活动增加且存在与复发无关的残疾进展。在“复发”队列中，我们在随访期间将273例患者确定为“稳定”（59.7%），114例患者为“活动”（24.9%），70例患者为“进展”（15.3%）。心血管危险因素（CVRF）和基线时年龄较大被确定为疾病进展的危险因素，而基线时使用疾病修饰治疗（DMT）有利于疾病稳定。随访期间使用DMT与疾病稳定而非活动相关，但与疾病进展无关。
50岁以上PwMS患者出现提示潜在活动性疾病的复发与持续的疾病活动和PIRA风险增加相关。CVRF的存在和基线时未使用DMT似乎是不良疾病进程的危险因素。DMT升级转换与疾病稳定而非活动相关，但与疾病进展无关。
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