Suboptimal B-cell depletion is associated with progression independent of relapse activity in multiple sclerosis patients treated with ocrelizumab

Background: While treatment with ocrelizumab has proven effective in preventing relapse-associated worsening (RAW) in relapsing multiple sclerosis (RMS), a significant number of patients experience progression independent of relapse activity (PIRA). Objectives: To investigate the association between B-cell depletion status and the risk of disability accumulation in RMS patients receiving ocrelizumab treatment. Methods: In this monocentric cohort study of 148 RMS patients (2017–2023), we categorized participants into three groups: no evidence of disease activity (NEDA), evidence of disease activity (EDA), and PIRA. B-cell counts were measured every 6–12 months, with suboptimal depletion defined as ⩾10 CD19+ B-cells/µL. Logistic regression and Cox proportional hazards models analyzed the relationship between B-cell depletion and disability progression. Results: Of 148 patients, 70 (47%) achieved NEDA, 51 (34%) showed EDA, and 25 (17%) developed PIRA. NEDA patients demonstrated significantly lower B-cell counts compared to EDA ( p < 0.01) and PIRA ( p < 0.001) groups. Insufficient B-cell depletion was the strongest PIRA predictor (OR 3.73, 95% CI: 2.50–5.43, p < 0.001) and increased EDSS progression risk (HR 0.50, 95% CI: 0.26–0.97, p = 0.039). Conclusions: PIRA occurs in the context of suboptimal B-cell depletion in RMS patients, highlighting the need for close monitoring and potential adjustment of infusion intervals.