B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.

  title={B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.},
  author={Stephen L. Hauser and Emmanuelle Waubant and Douglas L. Arnold and Timothy L. Vollmer and Jack P. Antel and Robert J. Fox and Amit Bar-Or and Michael A. Panzara and Neena Sarkar and Sunil Agarwal and Annette M Langer-Gould and Craig H. Smith},
  journal={The New England journal of medicine},
  volume={358 7},
BACKGROUND There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes. METHODS In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing-remitting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15. The primary end… 

Figures and Tables from this paper

Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Effectiveness of rituximab in reducing disease activity in patients with MS is shown, consistent with other observational studies.

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis

This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation, with a safety profile consistent with existing ofatumUMab data.

Rituximab for the treatment of multiple sclerosis: a review

A review of the pharmacokinetics, pharmacodynamics, clinical efficacy, safety profile and cost effectiveness aspects of RTX for the treatment of MS sheds light on the use of RTX as an alternative treatment option for MS management, while commenting the gaps of knowledge regarding this drug.

Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica.

Rituximab for relapsing-remitting multiple sclerosis.

The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) for patients with RRMS without restrictions regarding dosage, administration frequency and duration of treatment is evaluated.

Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis

A B-cell-depleting monoclonal antibody has recently been approved for MS therapy and is efficacious not only in relapsing forms of MS but also in some patients with primary progressive MS, suggesting that B cells may play a more important role in the pathogenesis of MS than previously appreciated.

De-escalating rituximab dose results in stability of clinical, radiological, and serum neurofilament levels in multiple sclerosis

De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12’months.

Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients

It was found that rituximab use was associated with a reduction in JCV antibody index values in MS patients, and reductions in immunoglobulins, IgM in particular, are seen in concert with J CV antibody reductions.



Rituximab Pharmacokinetics in Patients With Rheumatoid Arthritis: B‐Cell Levels Do Not Correlate With Clinical Response

The level of peripherally circulating B cells does not appear to correlate with a maintained clinical response in patients with rheumatoid arthritis, and the timing of rituximab retreatment should be based on clinical symptoms rather than peripheral B‐cell levels.

Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks.

At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.

Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis

Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images.

Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis

It is demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing-remitting multiple sclerosis in a well-tolerated fashion.

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis and hold promise as an effective treatment for relapsed multiple sclerosis.

New natural history of interferon-beta-treated relapsing multiple sclerosis.

IFN-beta slows progression in relapsing-remitting multiple sclerosis patients and shows a highly significant reduction in the incidence of secondary progression when compared with untreated patients.

Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology.

Data support an immunopathogenetic mechanism whereby B-cell follicles developing in the multiple sclerosis meninges exacerbate the detrimental effects of humoral immunity with a subsequent major impact on the integrity of the cortical structures.

The B cell response in multiple sclerosis

Recent studies that have analyzed the phenotypes of B cells in MS which infiltrate the CNS and the molecular features of their antigen-binding regions support the notion of a targeted and compartmentalized humoral response in MS.

Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis.

This study suggests that a compartmentalized B cell response occurs within the CNS during an ongoing inflammatory reaction, through a recapitulation of all stages of B cell differentiation observed in secondary lymphoid organs.

B-cells in multiple sclerosis.

Current treatments already target B-cell responses; consequently, this effect may be one explanation for the efficacy of these treatments in some types of MS.