Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica

- Rituximab, a B-cell depleting therapy, decreases disease activity in multiple sclerosis and neuromyelitis optica.
- T cell function in part depends on B cells; we sought to determine if CD4+ and CD8+ lymphocytes are affected by rituximab.
- We found brief decreases in CD4+ and CD8+ cells following first rituximab infusion that resolved 3-6 months after infusion.
- There were a small subset of patients with persistent CD4+ cells less than 500 or 200.
- Although in most cases transient, drops in CD4+ counts may increase risk of infection in a subset of rituximab recipients.

ObjectiveTo 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 patientsThis 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 measuresLinear 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.ResultsRituximab 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.ConclusionsAlthough transient, rituximab-induced decrease in CD4+ and CD8+ T-cells may increase the risk of infection in susceptible individuals.