Project Summary
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 on Treatment of Multiple Sclerosis. This research project is one of the studies PCORI awarded as part this program.
This research project is in progress. PCORI will post the research findings on this page within 90 days after the results are final.
What is the research about?
Multiple sclerosis, or MS, is a serious long-term health problem that affects more than 400,000 people in the United States. MS affects the brain and spinal cord. Symptoms include muscle weakness, trouble with coordination and balance, and thinking and memory problems. MS is a leading cause of disability among young adults in the United States. There is no cure for MS, but treatment can help manage symptoms.
Most people with MS have periods of new or worsening symptoms, called relapses, followed by periods of few or no symptoms, called remission. As MS goes on, symptoms slowly get worse without periods of getting better. Early symptoms may include trouble seeing, numbness, or weakness. Over time, patients may have a hard time walking and need a wheelchair.
In the early stages of MS, patients may take standard, first-line medicines to prevent relapses. Some aggressive medicines work better than first-line medicine for reducing relapse. However, aggressive medicines may cause serious side effects, such as higher risk of infections, autoimmune problems, cancers, and liver failure. Doctors don’t know if either method is better for preventing long-term MS disability. This study is comparing standard medicines versus aggressive medicines on delaying MS from reaching the stage where symptoms continue to get worse and lead to disability.
Who can this research help?
Patients with MS and their doctors can use findings from the study to better understand the risks and benefits of using stronger medicines to prevent or delay disability.
What is the research team doing?
The research team is enrolling 900 adults with MS at approximately 45 study sites throughout the United States and following up with them for up to 4.5 years. The team is assigning patients by chance to one of two groups. Half receive standard medicines, and half receive aggressive medicine. The study is comparing the overall effects of these classes of medicine on disability risk. The team is also looking at whether the medicines’ effect on future disability depends on whether patients are at high or low risk for disability at the start of the study.
The team is tracking patients who are at low risk for disability, but who have a relapse or changes on brain scans that suggest that the first medicine isn’t working well. The team reassigns these patients by chance to get either a different standard medicine or an aggressive medicine.
To assess differences in how often patients develop disability during early stages of MS, the team is following patients over time. The team is also tracking differences between groups in quality of life and disabling symptoms such as fatigue, and thinking and memory problems. To track disease progression, the team is using brain scans.
An advisory committee of people with MS, doctors, statistics experts, and patient advocacy groups is giving input on study design.
Research methods at a glance
|
Design Element |
Description |
|---|---|
| Design | Randomized controlled trial |
| Population | Adults ages 18–60 years with relapsing-remitting MS who did not receive chemotherapy previously or take specific MS medicines for a long period of time |
|
Interventions/Comparators |
|
| Outcomes |
Primary: long-term disability as assessed by neurologic examinations Secondary: patient-reported disability, fatigue, health-related quality of life |
| Timeframe | Up to 4.5 years of follow-up for primary outcome |
COVID-19-Related Study
Examining How the COVID-19 Pandemic Affected Adults with Relapsing Multiple Sclerosis -- The TREAT-MS Trial
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. Most people with MS have times when new or worsening symptoms occur over a short period, known as a relapses. Medicines called disease-modifying therapies, or DMTs, can prevent or reduce MS relapses.
Early in the COVID-19 pandemic, patients with MS had disruptions or delays in their care, like postponed or canceled in-person clinic visits. In this study, the research team wanted to learn how disruptions in care affected:
- MS relapses
- New areas of damage or scarring seen on magnetic resonance imaging, or MRI
- MS symptoms
The research team also wanted to know if anxiety or depression before the pandemic was related to changes in MS care during the pandemic.
What were the results?
Compared with patients who took DMTs the way their doctor prescribed, patients who did not were more likely to have a relapse or a change on their MRI.
Compared with patients who didn’t have postponed or canceled in-person clinic visits, those who did were more likely to have new or worsened MS symptoms.
Patients who had higher anxiety or depression before the pandemic were more likely to postpone or cancel in-person clinic visits. Anxiety and depression before the pandemic were not related to changes in how patients took DMTs.
Who was in the study?
The study included data from 369 patients with MS. All patients were receiving care from one of 41 clinics across the United States. Of these, 76 percent were White, 16 percent were Black or African American, 5 percent were another race, 1 percent were Asian, and 1 percent were multiracial; 9 percent were Hispanic. The average age was 36, and 69 percent were women.
What did the research team do?
The research team asked 369 patients from a larger PCORI clinical trial to take part in this study. The team surveyed patients at the start of the study and again every 12 weeks for 48 weeks. Surveys asked about changes in how patients were taking DMTs and postponed or canceled clinic visits. Patients reported on MS symptoms and relapses during routine follow-up visits.
The research team used data from 261 of the patients to look at the effect of anxiety or depression on changes in DMT use or MS care. Before the pandemic, these patients had filled out surveys about depression and anxiety.
Doctors who treat MS provided input during the study.
What were the limits of the study?
The study included volunteers from a larger PCORI trial. Results may have differed if the research team chose people by chance.
How can people use the results?
Patients with MS and their doctors can use the results when thinking about how disruptions in care during MS treatment may affect the health of MS patients.
| How this project fits under PCORI’s Research Priorities 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. |
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
Early in the COVID-19 pandemic, patients with multiple sclerosis (MS) experienced pandemic-related disruptions in care. Questions remained about how disruptions in disease-modifying therapy (DMT) adherence or clinical care affected MS relapses, new lesions seen on magnetic resonance imaging (MRI), or symptoms. Additionally, it was unknown if pre-pandemic anxiety and depression were associated with decisions to delay MS care during the pandemic.
Objective
To determine whether patients altered their DMT schedule or clinical care during the pandemic and if these changes were associated with breakthrough MS disease or new or worsened MS symptoms
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | 369 adults with MS and a subset of 261 adults with MS who had pre-pandemic anxiety and depression scores |
| Outcomes | MS breakthrough disease, defined as a relapse or a new lesion on MRI; new or worsened MS symptoms; DMT adherence; postponed or canceled in-person clinic visits |
| Data Collection Timeframe | March 2020–March 2022 |
This observational cohort study compared the effects of DMT adherence and changes to in-person clinical care during COVID-19 on breakthrough disease and new or worsened symptoms among people with MS. Researchers also compared the effect of pre-pandemic anxiety or depression on alterations in DMT adherence and disruptions in clinical care. Researchers invited patients from a randomized controlled trial (RCT) comparing higher efficacy DMTs versus moderate efficacy DMTs to participate.
At baseline and every 12 weeks for 48 weeks, patients completed surveys about disruptions in MS treatment or clinical care. Patients reported on MS symptoms during routine follow-up visits. To explore the association between pre-pandemic anxiety and depression with disruptions in DMT use or care, researchers analyzed data from patients who completed pre-pandemic surveys on anxiety and depression.
The study included 369 patients with MS treated at one of 41 clinics across the United States. Of these, 76% were White, 16% were Black or African American, 5% were another race, 1% were Asian, and 1% were multiracial; 9% were Hispanic. The average age was 36, and 69% were female.
Clinicians who treat MS provided input throughout the study.
Results
Compared to those without altered DMT adherence, patients with altered DMT adherence were more likely to have MS breakthrough disease (adjusted odds ratio [aOR]=3.68; 95% confidence interval [CI]: 2.06, 6.58). Compared to patients without clinic visit disruptions, patients with postponed or canceled in-person clinical care were more likely to have new or worsened MS symptoms (aOR=1.88; 95% CI: 1.17, 3.04).
Patients with higher pre-pandemic anxiety or depression were more likely to postpone or cancel in-person clinic visits during the pandemic (Anxiety: aOR=1.03; 95% CI: 1.00, 1.06; Depression: aOR=1.04; 95% CI: 1.01, 1.07). Pre-pandemic anxiety and depression were not significantly associated with altered DMT adherence.
Limitations
The study included volunteers from an RCT; selection bias may have affected findings.
Conclusions and Relevance
In this study, patients with MS with altered DMT adherence were more likely to have breakthrough disease. Patients with postponed or canceled in-person clinical care were more likely to have new or worsened MS symptoms. Patients with higher pre-pandemic anxiety or depression were more likely to postpone or cancel in-person visits.
| How this project fits under PCORI’s Research Priorities 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. |
Peer Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following: The reviewers asked the researchers to explain how they identified altered treatment for multiple sclerosis (MS) during the COVID-19 pandemic.
- The researchers provided definitions for several types of altered treatment such as altered medication adherence and delayed or canceled in-clinic care.
- The reviewers disagreed with the researchers’ assertions about the association between MS treatment and severe COVID-19 outcomes and cautioned the researchers to be more conservative in describing this association. The researchers revised the report to be more circumspect about the relationship between treatment type and COVID-19 illness severity, given the low number of patients in the analyses and the lack of descriptive information about COVID-19 illness.
- The reviewers also asked for more information justifying the analyses related to the association of depression and anxiety with treatment alteration and missed visits. The researchers maintained their sub-aim related to depression and anxiety but did not fully explain their reasoning behind this aim.
- The reviewers asked the researchers to consider the implications of this research project for other situations where MS care was altered or delayed. The researchers explained that understanding the types of altered care that were associated with worsening MS disease could help clinicians plan better for other situations where patients had to alter their care in the future.
Final Enhancement Report
This COVID-19 study's final enhancement report is expected to be available by May 2024.
