Abstract
BACKGROUND AND OBJECTIVES: Serum biomarker testing for multiple sclerosis has been increasing in popularity in research and clinical practice. Little evidence is available on influences of disease modifying therapy on serum biomarker levels. Interpretation of clinically available serum biomarkers in the context of each individual patient poses a greater challenge in this context. This study focuses on correlations between clinical variables and unique profile of serum biomarkers in the context of anti-CD20 treatment by ocrelizumab. METHODS: A cohort of multiple sclerosis patients without relapse in the last 12 months and the following 3 months who received serum biomarker testing with the Octave MSDA (Multiple Sclerosis Disease Activity) panel of 18 biomarkers between June 2023 and June 2024 was identified at the UCI Multiple Sclerosis Center. Clinical data was collected retrospectively. Data preparation, analysis and visualization were performed using R. RESULTS: A total of 118 MS patients without recent acute inflammatory activity were included (63 untreated and 55 on ocrelizumab). Longitudinal immunoglobulin data were available for 48 patients receiving ocrelizumab. Age-adjusted analyses revealed significantly elevated B-cell activating factor (BAFF) levels in the ocrelizumab group. In these patients, BAFF correlated inversely with IgG and IgA-but not IgM-levels. IgG declined over time in patients treated with ocrelizumab, with higher BAFF levels predicting lower IgG and IgA independent of treatment duration. Patients with elevated BAFF exhibited both lower baseline IgG and a more rapid IgG decline compared to those with lower BAFF. Elevated BAFF also correlated positively with markers of neuroaxonal injury, including neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP), Myelin oligodendrocyte glycoprotein (MOG), as well as with multiple pro-inflammatory biomarkers such as osteopontin (OPN), CXCL9, CXCL13, CCL20, TRAIL-R1, and CDCP1. DISCUSSION: This study provides insight into unique biomarker profile in patients on ocrelizumab. Increased BAFF was associated with lower IgG and IgA levels, biomarkers of neuroaxonal damage and inflammation in MS patients without recent acute inflammatory activity on ocrelizumab.