Discontinuation and dose reduction of rituximab in relapsing-remitting multiple sclerosis

Background: Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods: In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results: A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions: This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease

Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis : a Swedish cohort study

Background and purpose: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood. Methods: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated. Results: The mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated. Conclusions: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline