Predictors of B-cell repopulation in people with multiple sclerosis treated with ocrelizumab: insights from two large...

Evidence indicates that B-cell dynamics during ocrelizumab treatment vary among individuals with multiple sclerosis. However, our understanding of B-cell dynamics is incomplete. We aim to characterise temporal profiles of CD19+ B-cell repopulation and identify demographic and clinical predictors of B-cell dynamics.

This was a retrospective multicentre cohort study including people with multiple sclerosis treated with ocrelizumab for ≥180 days from two academic centres. Variables of interest were visualised to explore their associations with CD19+ B-cell count. Generalised linear mixed effect models and logistic mixed effect models were used to identify predictors of CD19+ B-cell counts and early B-cell repopulation (>0.01×10⁹ cells/L, 150-210 days post infusion). We have explored the patterns of early B-cell repopulation and relapse incidence within these groups.

567 participants, contributing 4592 CD19+ B-cell counts, were included. Younger age (β=-0.01, 95% CI -0.02 to -0.003), heavier weight (β=0.02, 95% CI 0.008 to 0.02), fewer ocrelizumab infusions (β=-0.07, 95% CI -0.08 to -0.06) and higher pre-ocrelizumab CD19+ B-cell counts (β=1.42, 95% CI 0.82 to 2.03) were associated with higher CD19+ B-cells during treatment. Pre-ocrelizumab CD19+ B-cells were higher in patients previously treated with natalizumab (mean B-cell count 0.57×10⁹ cells/L (IQR=0.34-0.85)) and lower in patients previously receiving sphingosine-1-phosphate receptor modulators (mean B-cell count 0.03×10⁹ cells/L (IQR=0.02-0.13)). Early B-cell repopulation was more likely in patients with prior early repopulation (OR=3.00, 95% CI 1.61 to 5.61). Relapse incidence did not differ between the four patterns of B-cell repopulation dynamics.

Age, weight, cumulative ocrelizumab exposure, pre-ocrelizumab CD19+ B-cell count and prior disease modifying therapy influence CD19+ B-cell repopulation during ocrelizumab treatment. With further elucidation of the association between B-cell dynamics and treatment effectiveness, these findings will help guide dosing of anti-CD20 therapies in the future.