Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica

Abstract

Objective: To determine the effect of a lower dose of rituximab in depleting B lymphocytes, maintaining low B-cell counts, and relapse in patients with neuromyelitis optica (NMO) and NMO spectrum disorders.

Methods: We treated 5 Chinese patients with deteriorating NMO and NMO spectrum disorders with a 100-mg IV infusion of rituximab once a week for 3 consecutive weeks, followed by additional infusion of the same dosage depending on circulating B-cell repopulation.

Results: This reduced dosage of rituximab was sufficient to deplete B cells and maintain low B-cell counts. None of the treated patients experienced relapse, and all patients exhibited stabilized or improved neurologic function during the 1-year follow-up period. MRI revealed the absence of new lesions, no enhancement in spinal cord and brain, a significant shrinkage of spinal cord segments, and a reduction/disappearance of previous brain lesions.

Conclusion: A lower dosage of rituximab may be sufficient in depleting B cells, maintaining low B-cell counts, and preventing disease progression in Chinese patients with NMO.

Figure 1. Kinetics of the B-cell population in patients treated with repeated dosage of 100 mg rituximab

(A) Reduced-dosage rituximab treatment regimen. We administered rituximab 100 mg IV, once per week for 3 consecutive weeks. Continued dosage was dependent on the percentage of circulating CD19⁺ B-cell counts from patients with neuromyelitis optica. Whenever it reached 1% of total lymphocyte population, rituximab 100 mg was reinfused except in patient 3 because a delay was caused by patient scheduling issues. (B) The repopulation of CD19⁺ B cells in patients with neuromyelitis optica during rituximab therapy. (C) The repopulation of CD19⁺CD27⁺ B cells parallels that of CD19⁺ B cells after rituximab treatment. In all 5 patients, whenever the percentage of CD19⁺ B cells reached 1%, CD19⁺CD27⁺ B cells were higher than 0.05%. We used simple whole-blood staining to monitor B-cell kinetics directly from the circulation. We immunostained whole-blood samples within 60 minutes of blood draw using antibodies directed against CD27/CD19 with isotype controls, followed by red blood cell lysis and immediate acquisition and analysis by flow cytometry. Before infusion, a percentage of circulating CD19⁺ cells among the total lymphocytes was determined as the baseline level. The percentage of CD19⁺ cells was determined again after 3 rituximab infusions at 4- to 8-week intervals. Infusion was stopped when these cells reached <1%, and reinfusion was continued when CD19⁺ cells exceeded 1% (A and B). All patients gave consent before receiving treatment.

Figure 2. Brain and spinal cord MRIs of a patient treated with repeated dosages of 100 mg rituximab

(A) Axial brain MRI scan of patient 3 illustrated multiple lesions bilaterally at bilateral basal ganglia, the thalamus, corpus callosum, and centrum ovale (arrows) on T2 fluid-attenuated inversion recovery before rituximab infusion. (B) Dramatic reduction and/or disappearance of lesions (arrows) were noted 1 year after rituximab therapy at the corresponding segments to panel A. (C–E) Sagittal T2W1 MRI of C1-T4 segments of spinal cord exhibits long segments of diffused signal enhancement before rituximab infusion (C); a gradual reduction in the extent of these lesions was observed between the sixth (D) and tenth (E) months during rituximab therapy. (F–H) No new lesions were found. Similar alterations in lesions were observed in T1-11 segments (arrows, F–H).