Abstract
Objective Ocrelizumab is a disease modifying therapy (DMT) for multiple sclerosis that depletes CD20+ B lymphocytes. Memory B-cells have been implicated in the pathogenesis of MS and there is emerging evidence suggesting a role for monitoring class-switched memory B (SMB) cells to guide re-dosing of anti-CD20 therapies in other CNS autoimmune conditions. This study aimed to examine B-cell repopulation and efficacy for ocrelizumab in a real-world setting.
Methods Single-centre retrospective observational study of patients with MS who had received ocrelizumab for ≥18 months with pre-infusion lymphocyte subsets and memory B-cell subtypes checked on ≥3 occasions. Repopulation cut-offs were >0.00x109/L for CD19+ B-cells and ≥0.0005x109/L for CD19+/CD27+/IgM-/IgD- SMB cells.
Results Sixty-three patients met the inclusion criteria. Of these, 25 (40%) had CD19+ B-cell repopulation and 46 (73%) had SMB repopulation at least once during follow-up. Previous DMT exposure (65% of patients) did not affect the incidence of CD19+ B-cell (34% vs 50%, p=0.34) or SMB cell (73% vs 72%, p>0.99) repopulation.
No patient experienced a confirmed relapse. Six patients (9.5%) developed new or enlarging T2 lesions on MRI >6 months after ocrelizumab initiation. The incidence of MRI activity was not influenced by CD19+ B-cell (8.0% vs 10.5%, p>0.99) or SMB cell (4.3% vs 23.5%, p=0.08) repopulation.
Conclusion CD19+ B-cell and SMB cell repopulation between infusions is common in patients treated with ocrelizumab, but this did not increase the risk of relapse or MRI activity in this study. Future studies may potentially delineate an SMB threshold for individualised dosing.
