To report OBOE (NCT02688985) long-term extension (LTE) findings post ocrelizumab treatment in people with relapsing multiple sclerosis (pwRMS).

OBOE is a prospective, open-label, randomized clinical trial assessing CSF biomarkers, clinical endpoints and magnetic resonance imaging (MRI) outcomes before and after ocrelizumab treatment. CSF neurofilament light chain (NfL) levels, CD19⁺ B-cell and CD3⁺ T-cell counts were significantly lower after 52-week ocrelizumab treatment (Cross, JAMA Neurol 2024); however, results of long-term ocrelizumab treatment are unknown. 

PwRMS received ocrelizumab 600-mg infusions every 24 weeks. CSF levels of NfL, CD19⁺ B cells and CD3⁺ T cells were assessed via lumbar puncture at baseline, Weeks 144 and 240. Values were reported as % change in medians between time points. Clinical, MRI and long-term safety outcomes were assessed. 

Among pwRMS (n=100), 83 (83%) continued LTE treatment, and 50 (50%) contributed analyzable CSF samples. CSF NfL was significantly reduced at Week 240 (−45.1%), as well as CD19⁺ B-cell (−92.4%) and T-cell levels (−68.1%) (P<0.001 for all). Suppression of MRI disease activity was maintained through the LTE. At Week 240, no pwRMS had T1 gadolinium-enhancing or new/enlarging T2 lesions and 91% of pwRMS remained relapse free after 5 years. No new safety signals were identified in the LTE.

Significant reductions in CSF NfL, B-cell and T-cell levels persisted over 5 years of ocrelizumab treatment, suggesting ongoing reduction of neuroaxonal injury and intrathecal inflammation. These results support long-term, sustained efficacy of ocrelizumab on reducing compartmentalized inflammation in pwRMS. Exploratory analyses of additional CSF candidate biomarkers (eg, glial fibrillary acidic protein, neurofilament heavy chain, soluble triggering receptor expressed on myeloid cells 2, chitinase-3-like protein 1 [YKL-40]) and characterization of their associations with relapsing and nonrelapsing MS biologies are ongoing.