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

外周 CD19+ B 细胞计数和输注间隔作为多发性硬化症和视神经脊髓炎/视神经脊髓炎谱系疾病的长期 B 细胞耗竭疗法的替代指标

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作者:Gisa Ellrichmann, Jan Bolz, Maren Peschke, Alexander Duscha, Kerstin Hellwig, De-Hyung Lee, Ralf A Linker, Ralf Gold, Aiden Haghikia

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.

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.

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.

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.

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.

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