Low-Dose Rituximab Safe, as Effective as High Dose in MS

Luciana Midaglia, MD

Results from a 2-center ambispective study presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, demonstrated that low doses of rituximab (Rituxan; Genentech/Biogen) seem to offer similar effectiveness with better safety profile than high doses when treating multiple sclerosis (MS).¹

Presented by Luciana Midaglia, MD, neurologist, Vall Hebron University Hospital, and the Multiple Sclerosis Centre of Catalonia, the study compared patients in the Barcelona center (BC; n = 249) who were administered 2 g of rituximab intravenously (IV) during at least 3 cycles, followed by 1 g every 6 months to those in the Girona center (GC; n = 54). In that cohort, 2 g rituximab was administered for at least the first cycle, followed by 500 mg every 6 months.

At baseline, mean annualized relapse rate (ARR) was 0.37 (±0.6) for those in the BC and 0.33 (±0.5) in the GC. At Year 1, ARR decreased to 0.05 (87.5%; P <.001) for BC compared to 0.03 (90.3%; P = .018) in the GC and to 0.08 (88.3%; P = 0.016) versus 0 (100%; P = .172) at Year 3.

Remaining stable or improvements on the Expanded Disability Status Scale (EDSS) score was found in 79.4% and 71.4% of progressive MS phenotypes in BC and GC, respectively. Median EDSS at baseline was 5.5 (BC: range, 1–9.0) versus 6.0 (GC: range, 1–8.0).

At Year 1, 2.7% of the BC population had contrast-enhancing lesions (CELs) and 19% reported with new T2 lesions. In comparison, 8% of those in the GC had CELs while 16% had new T2 lesions. At third year, 0% of the GC population documented CELs or new T2 lesions, whereas 12% of the BC reported CELs. Notably, there were 0 cases of CELs reported in the BC at third year.

In the BC, adverse events (AEs) occurred in 14.8% of patients during the first year compared to 4.1% at third year. Researchers noted that there was no difference in the dynamics of CD19% lymphocytes, while immunoglobulin (IgG) values in serum decreased significantly in the BC cohort throughout the first 3 years.

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.²

The agent has been often linked in use to treat other MS phenotypes such as myasthenia gravis and neuromyelitis optica spectrum disorder (NMOSD). A study published in May showed that treatment with rituximab performs better if initiated earlier after the onset of generalized symptoms in those with myasthenia gravis.³ Results from another study of patients with NMOSD suggest that first-line treatment with rituximab is more effective in suppressing clinical activity, independent of the antibody status, compared with mycophenolate mofetil (MMF) and other first-line immunosuppressants.⁴

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REFERENCES

1. 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

2. Stewart J. Rituxan FDA approval history. Drugs.com. drugs.com/history/rituxan.html. Updated September 30, 2019. Accessed Thursday September 24, 2020.

3. Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, Press R, Piehl F. Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis. JAMA Neurol. Published online May 4, 2020. doi: 10.1001/jamaneurol.2020.0851

4. Poupart J, Gioivannelli J, Deschamps R, et al. Evaluation of efficacy and tolerability of first-line therapies in NMOSD. Neurology. 2020;94:1-12. doi:10.1212/WNL.0000000000009245.