Project Summary
This research project is in progress. PCORI will post the research findings on this page within 90 days after the results are final. In the meantime, results have been published in peer-reviewed journals, as listed below.
PCORI has identified multiple sclerosis (MS) as an important research topic. Patients, clinicians, and others want 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 a funding initiative in 2015, Treatment of Multiple Sclerosis. This research project is one of the studies PCORI awarded as part this program.
What is the research about?
About 400,000 Americans have MS. This health problem affects the brain and spinal cord. MS can cause fatigue, numbness, vision changes, bladder problems, and mobility issues. Relapsing-remitting MS is the most common form of MS. Patients with this type of MS have attacks, with new or worse symptoms, followed by periods when symptoms get better.
Although there is no cure for MS, medicines can reduce the number and seriousness of MS attacks for people with the most common type of MS. Previous studies have shown that rituximab, a drug approved to treat some cancers and other diseases, can also treat relapsing-remitting MS. However, the US Food and Drug Administration hasn’t approved this medicine for MS. Also, doctors don’t know how well this medicine or other commonly used MS medicines work over many years, or whether they are safe when patients take them for a long time.
Researchers want to know how rituximab and other medicines compare over many years at improving patients’ quality of life. They want to know if the medicines work differently for patients who were just diagnosed with MS than they do for patients whose illness is more advanced. They also want to know how safe or effective rituximab is compared with other treatments for patients who have already tried another MS medicine.
Who can this research help?
This research can help doctors and patients decide what medicine to try first to treat relapsing-remitting MS. This research can also help doctors and patients choose a new medicine if another medicine doesn’t work as hoped.
What is the research team doing?
The research team is studying information from a Swedish database of patients with MS. The team also is collecting information from patients in Southern California who have MS. Every year for at least three years, researchers collect information about patients’ overall health, their MS, and quality of life. Using the national database helps researchers understand how medicines affect MS symptoms for a large number of patients. Using the information from patients in Southern California helps researchers find out how safe the medicines are over time. The research team expects to include information from about 6,000 patients by the end of the study. Because some patients started taking MS medicines several years before joining the study, researchers have information about how MS medicines affect these patients’ symptoms for up to nine years.
Researchers are looking at how well the medicines prevent MS symptoms and maintain quality of life. Researchers are also looking at whether safety issues like dangerous side effects cause patients to stop taking MS medicines.
The research team is working with patients with MS, families, caregivers, patient organizations, neurologists, scientists, and neurology organizations in the United States and Sweden. The group provides advice about how to carry out the study and what to measure. For example, the group suggested that the researchers measure both patient disability and quality of life.
Research methods at a glance
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | Adults aged 18 years and older with relapsing-remitting MS in Sweden and Southern California |
| Interventions/ Comparators |
|
| Outcomes |
Primary: disease progression, disease-related impact on quality of life Secondary: safety, including serious adverse reactions, relapse rate, number of contrast-enhancing lesions; time on drug, treatment satisfaction, quality of life, fatigue, employment |
| Timeframe | 3- to 9-year follow-up for primary outcomes |
COVID-19-Related Study
Comparing the Safety of Medicines to Treat MS during the COVID-19 Pandemic
Results Summary
In response to the COVID-19 public health crisis in 2020, PCORI launched an initiative to enhance existing research projects so that they could offer findings related to COVID-19. The initiative funded this study and others.
What was this COVID-19 study about?
Multiple sclerosis, or MS, is a health problem that affects the brain and spinal cord. In MS, the immune system mistakenly attacks the coating around the nerves.
Disease modifying therapies, or DMTs, help to reduce the disease activity of MS. Examples include rituximab, fingolimod, and interferon. DMTs change how the body’s immune system works. But they may increase the risk for infection. During the COVID-19 pandemic, questions arose about whether taking DMTs could lead to worse health outcomes from COVID-19.
In this project, the research team used data from health records and registries for people with MS in California and Sweden. The team looked at COVID-19-related health outcomes and immune response.
What were the results?
Health outcomes. Overall, people with MS were not at higher risk for worse outcomes from COVID-19.
- Among young and middle-aged people with MS, the risk of death from any cause was similar before and during the pandemic.
- During the pandemic, people with and without MS had a similar risk for a hospital stay, a stay in an intensive care unit, and death from COVID-19.
- Among people with MS who took rituximab, people who had higher and more recent doses had a higher risk of having severe COVID-19. But their risk of a hospital stay didn’t differ compared with people with lower and less recent doses.
Immune response. Antibodies and T cells help the body fight infection. People with MS who took rituximab or fingolimod had lower antibody levels for COVID-19 than people who took interferon. But people who took some DMTs, like rituximab, had similar levels of T cells for COVID-19 as people who took other DMTs and people without MS.
What did the research team do?
The research team did three studies that looked at health outcomes among:
- 17,692 people with MS versus 86,176 people without MS in Sweden. This study used registry data.
- 1,895 people with MS who took rituximab in California; 54% were Hispanic. This study used health record data.
- 172 people with MS who took rituximab in Sweden. This study used registry data.
The research team did two studies looking at immune responses among:
- 2,480 people with MS who took different DMTs in Sweden. People had blood tests between July and October 2020.
- 632 people with MS treated at a Swedish clinic and 15 people without MS in Sweden. People completed surveys about COVID-19 symptoms. People also had blood tests when they filled out surveys and then again 4 and 12 weeks after getting a COVID-19 vaccine.
People with MS, family members, patient advocacy organizations, clinicians, and MS scientists provided input for this study.
What were the limits of the study?
Because COVID-19 is a new illness, the research team didn’t have the information they needed to determine how many people to include in each study. Studies may not have had enough people to find differences in some outcomes.
How can people use the results?
People with MS and their doctors can use these results when considering MS treatments during the pandemic.
Professional Abstract
In response to the COVID-19 public health crisis in 2020, PCORI launched an initiative to enhance existing research projects so that they could offer findings related to COVID-19. The initiative funded this study and others.
Background
Disease modifying therapies (DMTs) alter the immune response. Although DMTs reduce multiple sclerosis (MS) progression, they may increase the risk for infection. During the COVID-19 pandemic, questions arose about whether DMTs affect the COVID-19 immune response for people with MS.
Objective
(1) To determine COVID-19 clinical outcomes among people with MS and among those treated with DMTs; (2) To examine humoral and T-cell immunity development among people with MS treated with DMTs.
Study Design
| Design Element | Description |
|---|---|
| Design |
5 observational and experimental cohort studies: Study 1: Retrospective observational cohort study Study 2: Retrospective observational cohort study Study 3: Experimental cohort study Study 4: Experimental cohort study Study 5: Registry linkage cohort study |
| Population |
People with MS treated at Kaiser Permanente Southern California or living in Sweden Data from Kaiser Permanente Southern California, including electronic health records Data from people in Sweden, including electronic health records, study registries, and national health registries |
| Outcomes |
Clinical outcomes: severity of COVID-19, hospitalization for COVID-19, all-cause mortality, admission to intensive care, death due to COVID-19 Immunologic outcomes: serological positivity to SARS-CoV-2 antigens and antibody levels, T-cell positivity to SARS-CoV-2 antigens |
| Data Collection Timeframe |
Pre-pandemic observations included data from March 1, 2015, to January 31, 2020 Pandemic observations included data from January 1, 2020, to June 30, 2021 |
These studies explored clinical outcomes and immune response after COVID-19 infection and vaccination among people with MS. Researchers analyzed data from laboratory results, health records, and health registries.
To look at clinical outcomes following COVID-19 infection, researchers conducted three studies:
- Study 1 included health record data from Kaiser Permanente Southern California for 1,895 people with MS who took rituximab; 54% were Hispanic.
- Study 2 included data from the Swedish MS registry for 172 people with MS who took rituximab or other DMTs.
- Study 5 included Swedish nationwide registry data for 17,692 people with MS and 86,176 people without MS matched for age, sex, and region.
To look at immunologic outcomes for COVID-19 infection or vaccination, researchers conducted two studies:
- Study 3 included clinical data and blood samples collected between July and October 2020 from 2,480 people with MS who took different DMTs in Sweden.
- Study 4 included 632 people with MS treated at a large Swedish MS clinic and 15 people without MS. People completed questionnaires about COVID-19 symptoms. Researchers collected blood samples at baseline and 4 and 12 weeks after COVID-19 vaccination.
People with MS, family members, advocacy organizations, clinicians, and MS scientists provided input for the project.
Results
Clinical outcomes
- Study 1. Odds of developing severe COVID-19 increased for people with higher versus lower rituximab doses (odds ratio [OR]=6.28; 95% confidence interval [CI]: 1.38, 28.5) and shorter versus longer time since last infusion (OR=0.32; 95% CI: 0.15, 0.69).
- Study 2. The association between rituximab timing and dose with risk for hospitalization did not differ significantly between people who were and were not hospitalized.
- Study 5. The relative risk for mortality among people with MS did not differ significantly during versus before the pandemic. People with and without MS had a similar risk for hospitalization (0.6% versus 0.2%), intensive care unit admission (0.1% versus 0.02%), and death from COVID-19 (0.1% versus 0.04%).
Immunologic outcomes
- Study 3. COVID-19 antibody levels differed moderately across people with MS who took different DMTs. Antibody levels were lower among people who took rituximab or fingolimod versus interferon.
- Study 4. People with MS who took rituximab or other B-cell-depleting DMTs had an intact COVID-19 T-cell response but partially reduced antibody response, compared with people with MS who took other DMTs or people without MS.
Limitations
The studies may have been underpowered to detect differences in some outcomes.
Conclusions and Relevance
Relative risk of severe COVID-19 was similar among people with and without MS. Medications like rituximab were associated with a reduced antibody response but an intact T-cell response.
Peer Review Summary
The Peer-Review Summary for this COVID-19 study will be posted here soon.
Final Enhancement Report
This COVID-19 study's final enhancement report is expected to be available by October 2023.
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.
Results of This Project
Related Journal Citations
Project Information
Patient / Caregiver Partners
- Jacques Roussel, Jr, (LA, USA)
- Jacques Roussel Senior (LA, USA)
- Linda Roussel (LA, USA)
- Julie Stachowiak (Arizona, USA)
- Deanna Stoner, Rituxan for MS facebook page (online support group) (LA, USA)
- Eva Helmersson, Swedish patient (Stockholm, SW)
- Swedish Patient Advocacy Group (Sweden)
- Nicholas LaRocca PhD, National Multiple Sclerosis Society (New York City, NY USA)
Other Stakeholder Partners
- American Academy of Neurology representative - Gary Gronseth, MD (Minneapolis, Minnesota, USA)
- Saty Saty-Murti,MD FAAN, Health Policy Consultant, Neurologist (Santa Barbara California, USA)
- Nazia Rashid, PharmD, MS, Kaiser Permanente Drug Information Services
- Professor Gavin Giovannoni MBBCh, PhD, FCP (S.A., Neurol.), FRCP, FRCPath, Author of Barts MS Blog
- Jan Hillert, Swedish MS register (Sweden)
- Tomas Olsson, PI other IMSE studies (Sweden)
- Swedish MS Society (Sweden)