Peripheral CD19 B-cell Counts and Infusion Intervals As a Surrogate for Long-term B-cell Depleting Therapy in Multiple Sclerosis and Neuromyelitis Optica/neuromyelitis Optica Spectrum Disorders

Background: With ocrelizumab another drug is available for the treatment of multiple sclerosis (MS). Little is known on the long-term use of ocrelizumab on immune cell subsets, and no surrogate markers are available. Rituximab (RTX) has been in off-label use for the treatment of MS, neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) for > 10 years.

Objective: We evaluated the long-term depletion and repopulation rate of peripheral CD19 B-cells as a potential surrogate for the clinical outcome, and whether it may serve for dosage and time-to-infusion decision making.

Methods: We evaluated the CD19 and CD4/8 T-cell counts in n = 153 patients treated with RTX (132 MS, 21 NMO/NMOSD). The dosages ranged from 250 to 2000 mg RTX. Depletion/repopulation rates of CD19 B-cells as well as long-term total lymphocyte cell counts, were assessed and corroborated with EDSS, ARR (annualized relapse rate), MRI, and time to reinfusion.

Results: CD19 B-cells' repopulation rate significantly varied depending on the dosage applied leading to individualized application intervals (mean 9.73 ± 0.528 months). Low/absent CD19 B-cell counts were associated with reduced ARR, EDSS, and GD-MRI-lesions. Long-term B-cell-depleting therapy led to a transiently skewed CD4/8 T-cell ratio due to reduced CD4 T-cells and absolute lymphocyte counts, which recovered after the second cycle.

Conclusion: Our data suggest that CD19 B-cell repopulation latency may serve as surrogate marker for individualized treatment strategies in MS and NMO/NMOSD, which proved clinically equally effective in our cohort as evaluated by previous studies.