Background: Ocrelizumab (OCR), a humanized, anti-CD20 antibody therapy approved for multiple sclerosis (MS), is given at 6-month intervals. Some patients on OCR report worsening of MS-related symptoms in the weeks leading up to their infusion (wearing-off phenomena), but there are no published reports quantifying symptom variation in relation to the timing of OCR infusions. Objectives: 1. To determine whether MS patients experience a change in symptom burden relative to time from OCR infusion; 2. To evaluate which demographic, clinical and laboratory (serum NfL levels and B-cell subsets) variables correlate with symptom variability. Methods: Prospective, observational, two-center study enrolled patients with relapsing and progressive forms of MS that are initiating OCR or who have been treated with OCR for ? 1 year. All patients receive MS care at NYU MS Care Center (NYU) in New York, NY, or the Elliot Lewis MS Center for MS (ELC) in Wellesley, MA. Patients aged 18-80 and with EDSS scores between 0-7 are eligible for enrollment. Over the course of one year, subjects are asked to complete four questionnaires (NeuroQol, SymptoMScreen, WPAI:MS, and a general questionnaire screening for new medical issues) at 6 pre-specified time points across 2 infusion cycles. Ocrelizumab concentration (PK), neurofilament light chain (NfL), B-cell subsets, and routine clinical labs are collected prior to each infusion. Results: 110 participants were enrolled and are actively followed in the study (55 from NYU/55 from ELC). At baseline visit, the mean age was 46.0+/-12.7 years; 64.6% were female; 31.8% were non-White; 20.0% were Hispanic/ Latino; disease duration was 12.6+/-9.6 years; OCR treatment duration was 2.8+/-1.0 years; mean EDSS was 3.3+/-2.1 (EDSS=4, n=41 (37.3%)). Breakdown by disease subtypes was: relapsing-remitting, n=68 (61.8%), secondary progressive, n=24 (21.8%), primary progressive, n=18 (16.4%). Among 58 patients who completed at least 2 questionnaires to date, the symptom burden, as assessed with the SymptoMScreen, was unchanged from week 4 post-infusion to week 12 post-infusion (p-values ranged from 0.2-0.9 for each of the 11 individual domains by Wilcoxon nonparametric test). Conclusions: SymBOLS, designed to assess for the wearing-off effect in OCR-treated patients, has successfully enrolled 110 patients across two US sites. Preliminary data suggest there are no changes to symptom burden during the first half of the infusion cycle. Additional data regarding changes during the second half of the cycle as well as NeuroQoL and work productivity (WPAI) data will be presented.