rituximab

#ACTRIMS2019 – No Evidence of Disease Activity Seen in POMS Adolescents Taking Rituximab, Small Study Shows

Data supporting the off-label use of rituximab in adolescents with pediatric-onset multiple sclerosis (POMS) was presented atĀ the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. The session, titledĀ ā€œNo Evidence of Disease Activity in the Majority of Pediatric-Onset Multiple Sclerosis Patients Receiving Rituximab,ā€…

Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports

Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, ā€œOcrelizumab Depletes CD20+Ā T Cells in Multiple Sclerosis Patients,ā€ was published in the journal Cells. AutoreactiveĀ immune T-cells, which attack the bodyā€™s own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy isĀ Genentechā€™s Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid ā€” the liquid surrounding the brain and spinal cord ā€” and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximabĀ (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatmentĀ that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximabā€™s clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical SchoolĀ in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patientsā€™ peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease forĀ a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes ā€” white blood cells that include T- and B-cells ā€” and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cellsā€™ fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. ā€œOur results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,ā€ the researchers wrote. ā€œThese findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,ā€ they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.

Top 10 Multiple Sclerosis Stories of 2018

Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, andĀ clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…

Switching from Rituxan to Ocrevus: An Interview with Dr. Timothy Vollmer on Both MS Treatments

A multiple sclerosis (MS) trial now underway in Colorado is assessing the safety and tolerability ofĀ switching fromĀ Rituxan (rituximab)Ā toĀ Ocrevus (ocrelizumab),Ā and its lead investigator, Dr. Timothy L. Vollmer, largely expects no problems. The neurologist believes the two GenentechĀ therapies ā€”Ā both antibody-based drugsĀ that target the CD20 molecule on B-cells ā€”…

Are Ocrevus and Rituxan Similar? Neurologists Respond to Patients’ Concerns

While manyĀ multiple sclerosis patients celebrated the recent approval of Ocrevus (ocrelizumab), others argued that the drug is largelyĀ a rebranded version ofĀ rituximab. Rituximab ā€” sold as Rituxan for indications like non-Hodgkin’s lymphoma,Ā chronic lymphocytic leukemia, andĀ rheumatoid arthritis ā€” is used off-label to treat relapsing MS. In online forums and social media,…

2 Cases of Brain Inflammation Raise Questions of Lemtrada Safety, But Link Uncertain

Two multiple sclerosis (MS) patients developed severe brain inflammation after being treatedĀ with Lemtrada (alemtuzumab), researchers report, raising questions about the therapy. A definite link between the lesions and the treatment, however, was not established. The patients’Ā symptomsĀ were successfully controlled with a blood transfusion and treatment with rituximab (brand name Rituxan,…

Top 10 Multiple Sclerosis Articles of 2016

A number ofĀ important discoveries, therapeutic developments, and events related to multiple sclerosis (MS) were reported dailyĀ by Multiple Sclerosis News Today throughout 2016. Now that the year is over, it is time to briefly review the articles that appealed most toĀ ourĀ readers. Here are the top 10 most-read articles of 2016, with…

Study of Potential Therapy for Relapsing MS That Targets B-Cells Now Recruiting Patients in US

Patients with relapsing multiple sclerosis (MS)Ā are being recruited forĀ aĀ clinical trial evaluatingĀ an experimental monoclonal antibody called ublituximab, the National MS Society announced in a recentĀ newsĀ release. The study, being conducted at seven U.S. sites, will enroll at least 24 patients, but this number can go up to 100. MSĀ is considered to be…

ICER Draft Report Evaluating Therapies for RRMS Now Open for Public Comment

TheĀ Institute of Clinical and Economic Review (ICER)Ā released the early draft of a paper intended toĀ informĀ a future report evaluating the effectiveness and value of disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS). The paper, called aĀ draft scopingĀ document, is titled “Disease Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: Effectiveness and…