Lower dose of rituximab demonstrates efficacy in MS with fewer side effects

Low doses of rituximab provided patients with MS an effective treatment option and an improved safety profile compared with higher doses of the agent, according to findings presented at MSVirtual2020.

“Rituximab is an anti-CD20 monoclonal antibody widely used as an off-label treatment for MS with a well-known efficacy and safety profile that is supported by two clinical trials and real-world experience,” Luciana Midaglia, MD, of the department of neurology-neuroimmunology at Vall Hebron University Hospital and the Multiple Sclerosis Centre of Catalonia, in Barcelona, Spain, said during her presentation. “However, rituximab dose has not yet been standardized.”

Midaglia and colleagues compared the safety and efficacy data for two different doses of rituximab: 2 g IV in at least 3 cycles, followed by 1 g every 6 months (BC group), vs. 2 g IV for at least the first cycle, followed by 500 mg every 6 months (GC group). The two-center, ambispective study included all patients treated with at least one cycle of rituximab through February 2020.

The researchers followed patients every 6 months with lab tests and performed MRIs at baseline, then on a yearly basis. They assessed annual relapse rate (ARR), contrast-enhancing lesions and new T2 lesions at years one and three of treatment, as well as Expanded Disability Scale Status (EDSS) changes at the final follow-up visit. They also reviewed the dynamics of CD19 lymphocyte and IG immunoglobulin, or IgG, values in serum and adverse events.

The study included 303 patients (BC = 249; GC = 54). The primary reason for rituximab initiation was clinical progression plus inflammatory activity (determined by clinical or radiological data or both) in 45.8% of patients from the BC cohort compared with 79.6% of patients from the GC cohort. The researchers found no differences between the two groups regarding age at rituximab onset, sex or disease duration.

Midaglia and colleagues recorded the following baseline values: mean ARR, 0.37±0.6 (BC) vs. 0.33±0.5 (GC); median EDSS, 5.5 (range, 1-9; BC) vs. 6 (range, 1-8; GC); and proportion of MRIs with contrast-enhancing lesions, 32.4% (BC) vs. 42.6% (GC). The ARR declined to 0.05 (87.5%; P < .001) for BC vs. 0.03 (90.3%; P = .018) for GC in the first year and to 0.08 (88.3%; P = .016) vs. 0 (100%; P = .172) in the third year.

When the researchers included only progressive MS phenotypes, 79.4% of patients in the BC cohort — compared with 71.4% of patients in the GC cohort — remained stable or improved according to the EDSS. MRI findings demonstrated that the percentage of patients with contrast-enhancing lesions and new T2 lesions was 2.7% for BC vs. 8% for GC and 19% for BC vs. 16% GC, respectively, at year 1 and 0% vs. 0% and 12% vs. 0%, respectively, at year 3.

The BC group reported a higher incidence of adverse events in the first year compared with the GC group (14.8% vs. 4.1%). The researchers observed no differences in the dynamics of CD19 lymphocytes, whereas IgG values diminished significantly among patients in the BC group in the first 3 years.

An ongoing phase 3 trial will evaluate two different dosing regimens — a standard dose of rituximab 500 mg every 6 months vs. a comparator dose of rituximab 500 mg every 12 months, Midaglia said in her presentation.

“In the treatment of MS, low doses of rituximab seem to offer similar effectiveness with better safety profile than high doses,” the researchers wrote.