Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica

Abstract

Objective: To investigate the effect of rituximab, a B-cell targeted therapy that is used in the treatment of multiple sclerosis (MS) and neuromyelitis optica (NMO), on other immune cells such as CD4+ and CD8+ T-cells in patients with MS and NMO.

Design, setting and patients: This is a retrospective study of all patients with MS or NMO who received at least one rituximab infusion at the UCSF MS tertiary care center between May 2005 and July 2011.

Main outcome measures: Linear mixed models were used to assess (a) how post-infusion cell counts changed over time compared to pre-infusion levels and one another; (b) whether the cell counts were different over multiple courses of rituximab; and (c) what was the dosing effect on the cell counts over time.

Results: Rituximab initially reduced CD4+ (by 26%, p=0.0005) and CD8+ (by 22%, p=0.0006) T-cells, although these changes were only transient. Subsequent treatments with rituximab did not result in a significant drop in CD4+ or CD8+ T-cells. Changes in other cell types were also typically more marked after the first cycle of rituximab than after additional treatments. The total dose of rituximab received did not appear to have a significant effect.

Conclusions: Although transient, rituximab-induced decrease in CD4+ and CD8+ T-cells may increase the risk of infection in susceptible individuals.

Keywords: Demyelinating diseases; Immunology; Monoclonal antibodies; Multiple sclerosis; Neuromyelitis optica; Rituximab.