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
Ellrichmann G, Bolz J, Peschke M, Duscha A, Hellwig K, Lee DH, Linker R, Gold R, Haghikia A (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 266
Pages Range: 57-67
Journal Issue: 1
DOI: 10.1007/s00415-018-9092-4
Abstract
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.
Authors with CRIS profile
Maren Peschke
Medizinische Fakultät
De-Hyung Lee
Medizinische Fakultät
Ralf Linker
Department of Neurology
Involved external institutions
Germany (DE)How to cite
APA:
Ellrichmann, G., Bolz, J., Peschke, M., Duscha, A., Hellwig, K., Lee, D.-H.,... Haghikia, A. (2019). 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. Journal of Neurology, 266(1), 57-67. https://doi.org/10.1007/s00415-018-9092-4
MLA:
Ellrichmann, Gisa, et al. "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." Journal of Neurology 266.1 (2019): 57-67.
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