Symptom stability throughout Ocrelizumab infusion cycle in patients with Multiple Sclerosis: final results of SYMptom Burden on Ocrelizumab, a Longitudinal Study (SYMBOLS)
Ilya Kister1, Cheongeun Oh1, Elizabeth Douglas2, Isabella O'Shea2, Tamar Bacon1, Andrew Bouley2, Ellen Lathi2, Joshua Katz2
1NYU School of Medicine, NY, 2The Elliot Lewis Center for Multiple Sclerosis Care
To determine whether symptom burden in Ocrelizumab (OCR)-treated MS patients varies over the 6-month infusion cycle.
OCR is a humanized anti-CD20 antibody therapy for multiple sclerosis (MS) given at 6-month intervals. Some patients report an increase in symptoms toward the end of the infusion cycle ("wearing off").

One-year, prospective, observational, two-center study (NCT04855617) enrolled MS patients aged 18-80 with EDSS scores between 0-7 who were treated with OCR for ≥ 1 year or were initiated on OCR. All patients were followed at NYU MS Care Center (NYU), New York, NY, and the Elliot Lewis MS Center (ELC), Wellesley, MA. Patients completed NeuroQol short forms, SymptoMScreen, work productivity (WPAI:MS), and medical screening questionnaires at 4-, 12-, and 24- weeks post-infusion for two consecutive infusion cycles as well as a post-study completion questionnaire.
115 participants were included in the study (n=53 NYU/n=62 ELC); 64% were female; 36% - non-White; baseline age - 46.2±12.5 years; disease duration -15.3±10.7 years; OCR treatment duration - 2.54 ±1.04 years; median (IQR) EDSS - 3.0 (1.5, 5.3); EDSS was >= 4 in 48 patients (42%). Paired Wilcoxon nonparametric tests used to evaluate the changes in outcome scores from pre- to post-infusion showed no significant changes on any NeuroQol and SymptoMScreen scales. Scores on two WPAI-MS subscales ("impairment while working due to health" and "overall work impairment") increased by 10% during the 2nd cycle (p-values=0.02 and 0.001) but not the 1st cycle. On the post-completion questionnaire, the percentage of patients who reported 'wearing off' always was 4%, usually - 33%, sometimes - 45%, and never - 17%.  
Although symptom burden remained stable throughout two OCR infusion cycles on multiple scales, most patients reported "wearing off" at least sometimes. We will discuss possible explanations for this discrepancy.