Results of a Spanish two-center study suggest that low doses of rituximab are equally effective as high doses, but have a superior safety profile. The anti-CD20 monoclonal antibody rituximab is not registered for the treatment of MS, but is widely used off-label. However, the rituximab dosing regimen has still not been standardized.
The key roles of B cells and humoral immunity in the pathogenesis of MS have been increasingly well substantiated. As a consequence, the anti-CD20 monoclonal antibody ocrelizumab has been approved for the treatment of primary progressive and relapsing MS (PPMS and RMS). This is not yet the case for rituximab. In a Spanish study, the efficacy and safety of 2 rituximab regimens were compared at 2 large MS centers in Barcelona and Girona .
The Barcelona center (BC) used a different regimen with higher doses of rituximab than the Girona center (GC). In the BC, at least 3 cycles of 2 g intravenously (IV) were followed by 1,000 mg every 6 months; in the GC, a minimum of 1 cycle of 2 g IV was followed by 500 mg every 6 months. Included were all 303 MS patients who had received at least 1 rituximab cycle before March 2020: 249 in the BC and 54 in the GC. At rituximab treatment onset, there were no differences in mean age, male/female ratio, and mean disease duration between the 2 centers. The main reason to start rituximab was clinical progression in combination with inflammatory activity (clinical, radiological, or both).
At baseline, mean annualized relapse rate (ARR) was 0.37 (BC) and 0.33 (GC); median Expanded Disability Status Scale (EDSS) was 5.5 and 6.0; and the proportion of MRI with contrast-enhancing lesions was 32.4% and 42.6%, respectively. In the BC and GC, mean ARR decreased to 0.05 (87.5%, P<0.001) and 0.03 (90.3%, P=0.018), respectively, in the first year of treatment. In the third year, ARR was 0.08 (88.3%, P=0.016) and 0.0 (100%, P=0.172). Of participants with progressive MS, EDSS remained stable or improved in 79.4% (BC) versus 71.4% (GC). The proportion of patients with contrast-enhancing lesions and new T2 lesions were 2.7% and 19% (BC) versus 8% and 16% (GC) after 1 year; this decreased to 0% and 12% (BC) versus 0% and 0% (GC) after 3 years.
In the first year, the incidence of adverse events was 14.8% in the BC versus 4.1% in the GC. There were no differences in the dynamics of CD19 lymphocyte percentages. IgG values decreased significantly in the BC cohort throughout the first 3 years, but not in the GC.
- Midaglia L, et al. MSVIRTUAL2020, Abstract PS01.05.