Low-Dose Rituximab Demonstrates Long-Term Benefit on Inflammatory MS Disease Activity

Malin Boremalm

Results from a retrospective observational study revealed that treatment with rituximab (Rituxan; Genentech/Biogen) has long-term effects on inflammatory disease activity in patients with multiple sclerosis (MS) after discontinuation or dose reduction.¹

Lead author Malin Boremalm, department of clinical Neurosciences, University Hospital of Umea, and colleagues also found that disease reactivation is rare among patients with MS who discontinued treatment for any reason, and that low-dose rituximab (<1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity.

Among a cohort of 225 patients treated with rituximab, researchers observed no differences regarding the annualized relapse rates (ARRs) during full dose versus reduced dose or off treatment (0.02 vs < 0.01 and 0.02; P = 0.09). The study included patients with either relapsing-remitting MS (RRMS) orclinically isolated syndrome (CIS), with patients serving as their own controls by contributing patient years on full dose, reduced dose, and off treatment.

The frequency of magnetic resonance imaging (MRI) scans with new gadolinium contrast per patient year was lower during the low-dose and super-low-dose treatment periods with 0.3 and 0.2 yearly MRI scans, respectively, compared to 1.0 and 0.7 MRI scans with gadolinium contrast per year for time on full dose and off treatment. Investigators of the study observed no significant differences in proportions of MRI scans with new or enhance T2 lesions (0.03 vs 0.01 and 0.03; P = 0.37) or proportion of MRI scans with contrast-enhancing lesions (CEL; < 0.01 vs 0 and 0.02; P = 0.22) between the treatment periods.

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"These findings could be useful to aid treatment decisions for RRMS patients during the COVID-19 pandemic during which the risk/benefit ratio of immunosuppressive treatment for MS may shift,” Boremalm et al wrote.

In total, 111 of the patients (49.3%) had discontinued treatment with rituximab at some point. The most common reason for discontinuation was adherence to a study protocol inferring discontinuation of rituximab after an accumulated dose of 2000 mg (36%) and the second most common reason was stable disease course (24.7%).

Boremalm and colleagues also compared the group of patients who regained disease activity (n = 15) with those who did not (n = 210) after dose reduction or discontinuation of rituximab. More (33% versus 14%) of the patients with disease activity had experienced breakthrough disease on full-dose treatment and they also had a higher baseline Expanded Disability Status Scale (EDSS; P = 0.01) compared with the group with no disease activity.

During the observation period, the latest available EDSS score was assessed at a mean of 8.1 (±1.9) and 6.0 (±2.0) years from baseline for patients with disease activity and patients with no disease activity, respectively. Furthermore, minimal changes in EDSS (–0.5 in both groups) were observed during the observation time.

Among the 15 participants with signs of disease activity after dose-reduction or discontinuation, 7 were on low dose, 1 were on super-low dose and 7 patients were off treatment at the time of their first episode of disease activity. The reasons for dose reduction in 7 of these patients were stable disease, otherwise a dose reduction to 500 mg yearly according to the regular treatment protocol at the clinic, and low immunoglobulin (IgG) levels for the patient on the super-low-dose treatment.

In total, 11 of the 15 patients who showed signs of disease activity after dose-reduction had new or enlarged T2 lesions on MRI, 2 of which also had 1 CEL.

Recently published research presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, demonstrated that low doses of rituximab seem to offer similar effectiveness with better safety profile than high doses when treating MS. In the third year of treatment, both dose cohorts did not experience any contrast-enhancing lesions, and only a small population in the Barcelona center showed new T2 lesions.²

Rituximab, an anit-CD20 monoclonal antibody, has been widely used as an off-label treatment for MS, but has not received FDA approval for this indication. It was first approved in November 1997 and has been indicated for the treatment of chronic lymphocytic leukemia, rheumatoid arthritis, Non-Hodgkin’s lymphoma, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus.³

REFERENCES

1. Boremalm M, Sundstrom P, Salzer J. Discontinuation and dose reduction of rituximab in relapsing-remitting multiple sclerosis. J Neurol. doi: 10.1007/s00415-021010399-8

2. Midaglia L, Alvarez GB, Cedeno RR, et al. Rituximab treatment for MS: an observational multicentric dose comparison. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract PS01.05

3. Stewart J. Rituxan FDA approval history. Drugs.com. drugs.com/history/rituxan.html. Updated September 30, 2019. Accessed February 1, 2021.