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
| Autor: | Ralf Gold, Aiden Haghikia, Maren Peschke, Gisa Ellrichmann, Kerstin Hellwig, De-Hyung Lee, Jan Bolz, Alexander Duscha, Ralf A. Linker |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty Multiple Sclerosis Lymphocyte T-Lymphocytes Antigens CD19 Dose-Response Relationship Immunologic Gastroenterology CD19 Monoclonal anti-CD20 antibody 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans 030212 general & internal medicine Lymphocyte Count B cell B-Lymphocytes Neuromyelitis optica Original Communication biology Surrogate endpoint business.industry Multiple sclerosis Neuromyelitis Optica Middle Aged medicine.disease CD19+ B-cell counts medicine.anatomical_structure Neurology biology.protein Neuromyelitis optica spectrum disorders Rituximab Ocrelizumab Female Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug Follow-Up Studies |
| Zdroj: | Journal of Neurology |
| ISSN: | 1432-1459 0340-5354 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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