Kister Ilya, Oh Cheongeun, Douglas Elizabeth A, Bacon Tamar E, O'Shea Isabella L, Parrotta Erica H, Bouley Andrew, Lathi Ellen, Katz Joshua
NYU Multiple Sclerosis Comprehensive Care Center (IK, TEB), Department of Neurology; Department of Population Health (CO), NYU Grossman School of Medicine, New York; The Elliot Lewis Center for Multiple Sclerosis Care (EAD, ILOS, AB, EL, JK), Wellesley, MA; and St. Peter's MS and Headache Center (EHP), Albany, NY.
Neurol Clin Pract. 2023 Oct;13(5):e200185. doi: 10.1212/CPJ.0000000000200185. Epub 2023 Sep 5.
Some patients with multiple sclerosis (MS) receiving ocrelizumab (OCR) report worsening symptoms toward the end of the 6-month infusion cycle ('wearing off'). The objective of our study was to comprehensively assess changes in symptom burden across 2 consecutive OCR infusion cycles.
SYMptom Burden on Ocrelizumab, a Longitudinal Study (SymBOLS; NCT04855617) was an investigator-initiated, 2-center study of patients with MS starting or receiving OCR. Patients' symptoms were assessed with NeuroQoL short forms, SymptoMScreen, and Work Productivity and Activity Impairment Questionnaire at the start-cycle, mid-cycle, and end-cycle time points in each of the 2 infusion cycles. Symptom scores at the 3 time points within each cycle were compared with repeated-measures ANOVA or the Friedman rank-sum test for non-normal variables. The proportions of patients with a meaningful symptomatic change from the start to the end of each infusion cycle were calculated, and patients whose symptoms improved, worsened, and stayed the same from the start to the end of the cycle were compared with respect to demographic and clinical characteristics.
One hundred three patients with MS provided longitudinal data for analyses (mean age [SD]: 46.7 [12.2] years, 68% female, 33% non-White, disease duration: 15.5 [5] years, 41% with the Extended Disability Status Scale score >3). On a group level, NeuroQoL and SymptoMScreen scores mostly remained stable or even improved slightly toward the end of each cycle. On an individual level, symptoms remained unchanged across either cycle for most patients, and meaningful symptom worsening from the start to the end of the cycle was no more common than improvement. Meaningful change in symptoms in both cycles was very rare and generally in the direction of improvement toward the end cycle. Despite the lack of evidence for symptom worsening with a longer time from infusion, 54% of patients endorsed feeling of "wearing off" at least sometimes, most commonly as an increase in fatigue.
Our prospective study failed to uncover evidence for the worsening of symptoms with a longer time from OCR infusion. These findings cast doubt on the existence of wearing off as a physiologic phenomenon in OCR-treated patients with MS. The perception of wearing off is likely the result of natural fluctuations in MS symptoms and attribution bias.
一些接受奥瑞珠单抗（OCR）治疗的多发性硬化症（MS）患者在6个月的输注周期接近尾声时报告症状恶化（“药效消退”）。我们研究的目的是全面评估连续两个OCR输注周期中症状负担的变化。
奥瑞珠单抗症状负担纵向研究（SymBOLS；NCT04855617）是一项由研究者发起的、在两个中心开展的针对开始使用或正在接受OCR治疗的MS患者的研究。在每个输注周期的起始、中间和结束时间点，使用神经生活质量简表、症状筛查量表以及工作效率和活动障碍问卷对患者的症状进行评估。每个周期内三个时间点的症状评分通过重复测量方差分析或针对非正态变量的弗里德曼秩和检验进行比较。计算每个输注周期开始到结束时有显著症状变化的患者比例，并比较从周期开始到结束症状改善、恶化和不变的患者的人口统计学和临床特征。
103例MS患者提供了用于分析的纵向数据（平均年龄[标准差]：46.7[12.2]岁，68%为女性，33%为非白人，病程：15.5[5]年，41%的扩展残疾状态量表评分>3）。在组水平上，神经生活质量和症状筛查量表评分在每个周期接近尾声时大多保持稳定甚至略有改善。在个体水平上，大多数患者在两个周期中的症状均无变化，从周期开始到结束有显著症状恶化的情况并不比改善更为常见。两个周期中症状的显著变化非常罕见，且总体上在周期结束时呈改善趋势。尽管缺乏证据表明随着输注后时间延长症状会恶化，但54%的患者至少有时会认可“药效消退”的感觉，最常见的是疲劳感增加。
我们的前瞻性研究未能发现随着OCR输注后时间延长症状恶化的证据。这些发现对OCR治疗的MS患者中作为一种生理现象的药效消退的存在提出了质疑。药效消退的认知可能是MS症状自然波动和归因偏差的结果。
