Results Summary

What was the research about?

Multiple sclerosis, or MS, is a health problem that affects the central nervous system. It causes problems with vision, balance, muscle control, and daily activities. Symptoms tend to last a short time at first but may become permanent.

Disease modifying therapies, or DMTs, help reduce MS disease activity. But DMTs vary in how effective and safe they are. People often switch DMTs until they find one that works. In other countries, doctors use a DMT called rituximab. In the United States, rituximab isn’t approved to treat MS.

In this study, the research team looked at the safety and effectiveness of rituximab compared with six other DMTs. The team looked separately at patients who started a DMT and patients who switched to a new DMT.

What were the results?

After three years, patients taking rituximab did about as well as those taking other DMTs. Overall, for patients taking these medicines, MS symptoms had less of an impact on well-being. The percentage of patients who had worsening disability from MS or whose MS affected their daily life was similar. But compared with other DMTs, more patients taking rituximab stayed on their medicine, and more had no MS symptoms. Also, compared with other DMTs, patients taking rituximab had:

  • Fewer MS relapses, or symptoms that returned after going away, except among patients starting natalizumab
  • Fewer MS relapses after childbirth

Patients who started rituximab were more satisfied with treatment than patients who started other DMTs, except natalizumab.

Patients taking rituximab and other DMTs didn’t differ in quality of life, cancer, heart problems, or problems during pregnancy.

Switching medicines. Patients who switched to rituximab had higher rates of a hospital stay for a serious infection than those who switched to other DMTs. Compared with switching to rituximab, patients who switched to:

  • Fingolimod had less fatigue
  • Natalizumab had faster cognitive processing

Satisfaction didn’t differ among patients who switched to rituximab or other DMTs, except dimethyl fumarate, which had lower satisfaction.

What did the research team do?

The research team enrolled 3,903 adults with MS. All received care at one of seven clinics in Sweden. Doctors prescribed a DMT to each patient. The team reviewed health records to see which DMTs patients took and to assess study outcomes. Among patients starting DMTs, the average age was 35, and 71 percent were women. Among patients switching DMTs, the average age was 40, and 72 percent were women.

To assess safety, the research team also looked at:

  • Registry data for 6,421 patients with MS in Sweden
  • Health records for 12,155 patients with MS in California

Patients with MS, caregivers, patient organizations, and doctors gave input during the study.

What were the limits of the study?

Fewer patients had worsening MS or safety outcomes than expected. As a result, it was hard to detect differences between DMTs.

Future research could compare DMTs for longer periods of time to better detect differences in outcomes.

How can people use the results?

Patients with MS and their doctors can use these results when considering DMTs to treat MS.

PCORI identified multiple sclerosis (MS) as an important research topic. People with MS, clinicians, and others wanted to learn how different treatment strategies, aimed at changing specific symptoms or the overall course of MS, affect patients’ symptoms and quality of life. To address this issue, PCORI launched an initiative in 2015 on Treatment of Multiple Sclerosis. The initiative funded this research project and others.

Final Research Report

This project's final research report is expected to be available by May 2024.

Journal Citations

Article Highlight: Through a research funding enhancement, which this study received in 2020 to quickly initiate new research related to COVID-19, the team comparing the safety and effectiveness of long-term medicines used to treat multiple sclerosis (MS) used its enhancement to see whether patients taking these drugs were more likely to be hospitalized or die from COVID-19 than the public. As reported in the Annals of Clinical and Translational Neurology, patients with MS treated with the drug rituximab were at increased risk of hospitalization but not ventilatory support or death from COVID‐19 compared to the general population.

Related Journal Citations

Peer-Review Summary

The Peer-Review Summary for this study will be posted here soon.

Conflict of Interest Disclosures

Project Information

Fredrik Piehl, MD, PhD
Karolinska Institute (Sweden)
Rituximab in Multiple Sclerosis: A Comparative Study on Effectiveness, Safety, and Patient-Reported Outcomes

Key Dates

July 2016
September 2023

Study Registration Information


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Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
Last updated: October 16, 2023