Early B-cell repopulation occurs in people with Multiple Sclerosis (pwMS) receiving B-cell depleting therapies (BCD). There is limited knowledge on the potential predictors of early B-cell repopulation and its clinical implications.

We examined the (1) association between body mass index (BMI) and early B-cell repopulation and (2) association between early B-cell repopulation and subsequent clinical outcomes in pwMS on BCD.

N/A

We conducted a retrospective study in two academic centers. From pwMS who completed at least one full cycle of BCD (Ocrelizumab or Rituximab), we obtained BMI, CD19%, demographic and clinical features as well as outcomes in relation to BCD administration. We operationally defined early B-cell repopulation as CD19% value of ≥2% within 4.5-6 months following infusion. The primary clinical outcomes included annualized relapse rate and confirmed disability worsening (based on patient determined disease steps). Additional clinical outcomes in subgroup analysis included functional testing scores and optic coherence tomography metrics.  We performed covariate-adjusted regression analyses.

The study included 293 pwMS (mean age 45.86±12.75 years, 70% women).  Higher BMI was significantly associated with greater likelihood of early B-cell repopulation (estimate=1.08, 95%CI [1.05, 1.11], p<0.001) after confounder adjustment. The same association persisted in subgroup analysis examining Ocrelizumab or Rituximab separately. Race/ethnicity was independently associated with early B-cell repopulation, with non-white and/or Hispanic PwMS being 1.40 times more likely to experience early B-cell repopulation than non-Hispanic white pwMS. Early B-cell repopulation was not significantly associated with increased annualized relapse rate or confirmed patient-reported disability progression or worsening of any of the examined secondary MS outcomes.

Among pwMS receiving BCD, higher BMI and racial/ethnic minorities are associated with early B-cell repopulation, but early B-cell repopulation is not associated with worse clinical outcomes. Larger prospective studies with longer follow-up duration are warranted to confirm these findings.