B-Cell Depletion With Rituximab In Relapsing/Remitting Multiple Sclerosis
HERMES Trial Group
Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH
N Engl J Med 2008 Feb 14;358(7):676-88
University of California at San Francisco, Department of Neurology, San Francisco, CA 94143-0114, USA
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.
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 point was the total count of Gadolinium-enhancing Lesions detected on Magnetic Resonance Imaging scans of the Brain at weeks 12, 16, 20, and 24.
Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse.
As compared with patients who received placebo, patients who received Rituximab had reduced counts of total Gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P < 0.001)
And, of total new Gadolinium-enhancing lesions over the same period (P < 0.001); these results were sustained for 48 weeks (P < 0.001).
As compared with patients in the placebo group, the proportion of patients in the Rituximab group with relapses was significantly reduced at week 24 (14.5% vs. 34.3%, P=0.02) and week 48 (20.3% vs. 40.0%, P=0.04).
More patients in the Rituximab group than in the placebo group had adverse events within 24 hours after the first infusion, most of which were mild-to-moderate events; after the second infusion, the numbers of events were similar in the two groups.
A single course of Rituximab reduced inflammatory Brain lesions and clinical relapses for 48 weeks.
This trial was not designed to assess long-term safety or to detect uncommon adverse events. The data provide evidence of B-Cell involvement in the pathophysiology of Relapsing/Remitting Multiple Sclerosis.
Copyright 2008 Massachusetts Medical Society.
The Potential Utility Of B-Cell-Directed Biologic Therapy In Autoimmune Diseases
Rheumatol Int 2008 Jan;28(3):205-15
University of Southern California, Keck School of Medicine, Division of Rheumatology, HMR 711, 2011 Zonal Avenue, Los Angeles, CA, 90033, USA
Increasing awareness of the importance of aberrant B-Cell regulation in Autoimmunity has driven the clinical development of novel B-Cell-directed biologic therapies with the potential to treat a range of Autoimmune Disorders.
The first of these drugs-Rituximab, a chimeric MonoClonal AntiBody against the B-Cell-specific surface marker CD20-was recently approved for treating Rheumatoid Arthritis in patients with an inadequate response to other biologic therapies.
The aim of this review is to discuss the potential use of Rituximab in the management of Other Autoimmune Disorders.
Results from early phase clinical trials indicate that Rituximab may provide clinical benefit in Systemic Lupus Erythematosus, Sjögren's Syndrome, Vasculitis, and ThrombocytoPenic Purpura.
Numerous case reports and several small pilot studies have also been published reporting the use of Rituximab in conditions such as Myositis, AntiPhospholipid Syndrome, Still's Disease, and Multiple Sclerosis.
In general, the results from these preliminary studies encourage further testing of Rituximab therapy in formalized clinical trials.
Based on results published to date, it is concluded that Rituximab, together with other B-Cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these Difficult-To-Treat Autoimmune Disorders.
Relapses After Treatment With Rituximab In A Patient With Multiple Sclerosis And Anti Myelin-Associated Glycoprotein Polyneuropathy
Benedetti L, Franciotta D, Vigo T, Grandis M, Fiorina E, Ghiglione E, Roccatagliata L, Mancardi GL, Uccelli A, Schenone A
Arch Neurol 2007 Oct;64(10):1531-3
University of Genova, Department of NeuroSciences, Ophthalmology, and Genetics, Via De Toni 5, 16132 Genova, Italy
To describe the unique case of a patient with Multiple Sclerosis (MS) and Anti-Myelin-Associated Glycoprotein (MAG) polyneuropathy who developed MS relapses after treatment with Rituximab.
Design & Setting
Case report. University of Genova, Department of NeuroSciences, Ophthalmology, and Genetics, Genova, Italy.
Patient A 59-year-old man with an 18-year history of MS presented with an unusually rapid progression of Paraparesis with HypoPallesthesia and Areflexia in 4 limbs.
NeuroPhysiological and Serological studies led to the diagnosis of Anti-MAG PolyNeuropathy.
CerebroSpinal Fluid analysis disclosed the loss of OligoClonal IgG Bands that were previously detected at MS onset. Intervention Rituximab was administered at a dosage of 375 mg/m(2)/wk for 4 weeks.
The patient developed 2 CorticoSteroid-responsive MS relapses with improvement of the PolyNeuropathy.
Rituximab can be effective in Anti-MAG PolyNeuropathy but can possibly lead to unexpected consequences in individuals with MS.