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.