Impact of treatment mechanism on octave MSDA pathway scores in patients receiving ocrelizumab or natalizumab

Objectives To compare MSDA Score and pathway scores between patients treated with ocrelizumab and natalizumab in real-world MS population. Methods We conducted a cross-sectional observational study of patients treated with ocrelizumab or natalizumab at a tertiary MS center between June 2023 and February 2025. Octave MSDA results were linked to clinical and MRI data from electronic health records. Group differences in MSDA composite and pathway scores were evaluated using ordinal regression models adjusted for demographic and disease-related covariates. Results A total of 152 patients were included (105 ocrelizumab, and 47 natalizumab). Except for two natalizumab-treated patients (≥ 4 months), all patients had been on their current DMT for at least 6 months. Patients treated with ocrelizumab were significantly more likely to have low MSDA scores (MSDA ≤ 4) compared to those treated with natalizumab (98.1% vs. 66%), despite similar clinical and MRI outcomes. Patients on ocrelizumab also had lower scores in three biological pathways, including neuroinflammation (p < 0.001), immunomodulation (p < 0.001), and myelin biology (p = 0.002). Conclusions Ocrelizumab-treated patients showed significantly lower Octave MSDA composite scores compared with natalizumab, independent of clinical and MRI findings, highlighting the importance of considering DMT mechanisms when interpreting serum biomarker profiles.