Project Summary
PCORI supports Patient-Powered Research Networks (PPRNs), communities of patients participating in clinical research, as part of the National Patient-Centered Clinical Research Network (PCORnet). In 2017, PCORI launched an initiative on Partnerships to Conduct Research within PCORnet to support the PPRNs in conducting comparative clinical effectiveness research on questions that are important to patients and other stakeholders. The initiative funded this project and others.
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.
What is the research about?
The immune system works to protect the body from infections. In inflammatory bowel disease, or IBD, the immune system attacks healthy cells by mistake. Crohn’s disease, or CD, and ulcerative colitis, or UC, are IBDs that cause long-term diarrhea and stomach pain. IBD can reduce quality of life and even lead to death. CD and UC affect more than 1.5 million Americans.
Biologics and small molecules are types of medicine that reduce inflammation. A group of biologics, called anti-TNFs, are the first option for treating moderate to severe CD and UC. But for up to 80 percent of patients, the medicine doesn’t work as well over time or stops working.
In this study, the research team is comparing how new biologic and small molecule treatments work for patients when anti-TNF medicines don’t work. The team is comparing a medicine called vedolizumab with another called ustekinumab for patients with CD. They are also comparing vedolizumab with a medicine called tofacitinib for patients with UC.
Who can this research help?
Results from this study can help patients who don’t respond to anti-TNFs and their doctors when considering treatment options.
What is the research team doing?
The research team is looking at data from adults age 18 or older. They are including at least 180 adults with CD and at least 180 adults with UC who are starting one of the newer medicines after not responding to an anti-TNF medicine. To identify patients, the team is working with 18 clinics across the country, health plans, a network of patients interested in research on IBD, and another research study. The team is following up with patients six months after they start their new medicine. The team is asking patients about their experiences of pain, fatigue, digestive symptoms, and other outcomes that matter to patients.
The research team is also looking at claims data for another group of patients who are starting one of the medicines after not responding to an anti-TNF medicine. Claims data is information from health insurance companies about the kinds of treatment a patient gets. It allows researchers to see how patients respond to treatment in the real world. The team is studying how long patients stay on their new medicine and whether they are hospitalized or have surgery over a one-year period.
Patients with CD and UC are working with the research team to plan the study.
Research methods at a glance
| Design Elements | Description |
|---|---|
| Design | Aim 1: prospective cohort study Aim 2: retrospective cohort study |
| Population | Aim 1: adults with CD who are starting ustekinumab or vedolizumab after no response to an anti-TNF medicine Aim 2: adults with UC who are starting tofacitinib or vedolizumab after no response to an anti-TNF medicine |
| Interventions/ Comparators |
Aim 1:
|
| Outcomes | Aim 1: Primary: fatigue, pain interference Secondary: disease activity and social satisfaction Aim 2: Persistence on therapy for at least 1 year, absence of hospitalization, absence of surgery |
| Timeframe | Aim 1: 6-month follow-up for primary outcomes Aim 2: At least 1-year follow-up from treatment initiation |
COVID-19-Related Study
Do Medicines for Inflammatory Bowel Disease Affect the Risk of COVID-19 Infection?
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?
With inflammatory bowel disease, or IBD, the immune system harms healthy cells in the body. Patients with IBD have symptoms like stomach pain and long-term diarrhea.
To treat IBD, people can take different types of medicine that limit the body’s immune system response. But these medicines may lower the body’s defenses and increase the chance of getting severe COVID-19.
This study had two parts. First, the research team wanted to learn if taking IBD medicines increased the chance of getting COVID-19 infection. They looked at seven types of IBD medicines:
- Corticosteroids
- Aminosalicylates
- Thiopurines
- Anti-integrins
- Janus kinase (JAK) inhibitors
- Anti-interleukin (anti-IL) 12/23s
- Anti-tumor necrosis factor (TNF) agents
Second, the research team looked at how these medicines affected the risk that patients would have a hospital stay, be placed on a ventilator, or die due to COVID-19.
What were the results?
COVID-19 infection rates didn’t differ between patients who did and didn’t use IBD medicines.
Compared with patients who didn’t use corticosteroids, patients who used them had a higher risk of:
- Having a hospital stay due to COVID-19
- Being placed on a ventilator due to COVID-19
- Dying due to COVID-19
Patients who used anti-TNF or aminosalicylate medicines had a lower risk of going to the hospital due to COVID-19 than patients who didn’t use them. The other medicines weren’t related to the study outcomes.
Who was in the study?
The first part of the study included 3,953 adult patients with IBD. Of these patients, 99 percent were White, and 1 percent were African American. The average age was 47, and 67 percent were women.
The second part looked at insurance claims for 102,986 patients enrolled in two large, national health plans. The average age was 53, and 55 percent were women.
What did the research team do?
In the first part of the study, the research team sent online surveys to patients with IBD who were already participating in ongoing studies sponsored by the Crohn’s and Colitis Foundation. The surveys asked about other illnesses, medicine use, and COVID-19 test results between April 2020 and August 2021. The team sent surveys at the start of the study; two, four, six, and eight weeks later; and then every six months.
In the second part, the research team reviewed insurance claims data for patients with IBD between August 2019 and August 2021. The team looked at the types of IBD medicines patients used, hospital stays, use of ventilators, and deaths from COVID‑19.
What were the limits of the study?
People started to receive COVID-19 vaccines during the study. Vaccines may have affected the number of COVID-19 infections or COVID-19 severity. The research team didn’t assign patients to IBD medicine or no IBD medicine by chance. As a result, the team can’t say for sure whether the IBD medicines caused the outcomes studied.
How can people use the results?
Patients with IBD can use the results to help understand their risk of having severe COVID-19 when taking medicines for IBD.
| How this project fits under PCORI’s Research Priorities The research reported in this results summary was conducted using PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® is intended to improve the nation’s capacity to conduct health research, particularly comparative effectiveness research (CER), efficiently by creating a large, highly representative network for conducting clinical outcomes research. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute® (PCORI®). |
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
Patients with inflammatory bowel disease (IBD) may be at increased risk for developing COVID-19 due to immune dysfunction. To manage IBD, patients often take immunosuppressant medications. During the pandemic, questions arose about whether immunosuppressant medications increase the risk of contracting and developing severe COVID-19.
Objective
To determine whether immunosuppressant medication use is associated with increased risk of COVID-19 infection, hospital admission, ventilator use, or death due to COVID-19 among patients with IBD
Study Design
| Design Element | Description |
|---|---|
| Design | Prospective cohort study, retrospective cohort study |
| Population |
Prospective cohort: 3,953 adult patients with IBD who were previously enrolled in three studies funded by the Crohn’s and Colitis Foundation Retrospective cohort: Insurance claims from 102,986 adult patients with IBD who were enrolled in two large, nationwide health plans |
| Outcomes |
Prospective cohort: self-reported COVID-19 infection confirmed via PCR or antigen test Retrospective cohort: hospital admission due to COVID-19, ventilator use due to COVID-19, death due to COVID 19 |
| Data Collection Timeframe |
Prospective cohort: April 2020–August 2021 Retrospective cohort: August 2019–August 2021 |
These prospective and retrospective cohort studies aimed to understand the association between immunosuppressant medication use and COVID-19 infection and the risk of severe COVID-19 outcomes in patients with IBD.
In the prospective cohort study, researchers sent online surveys to patients with IBD who were participating in several ongoing studies funded by the Crohn’s and Colitis Foundation. The surveys included questions on comorbidities, medication use, and COVID-19 infection between April 2020 and August 2021. Researchers sent surveys at baseline; two, four, six, and eight weeks later; and then every six months. The prospective cohort included 3,953 adult patients. Of these patients, 99% were White, and 1% were African American. The average age was 47, and 67% were female.
In the retrospective cohort study, researchers analyzed health insurance claims data from patients with IBD in two large, nationwide health plans between August 2019 and August 2021, with the pandemic period starting in March 2020. Researchers reviewed claims to determine whether patients used seven classes of immunosuppressant medication, including corticosteroids, aminosalicylates, thiopurines, anti-integrins, Janus kinase (JAK) inhibitors, anti-interleukin-12/23 agents, and anti-tumor necrosis factor (TNF) medications. They also reviewed hospitalization, ventilator use, and death due to COVID-19. Researchers analyzed claims data from 102,986 patients enrolled in the two health plans. The average age of patients was 53, and 55% were female.
Patients with IBD helped design the study.
Results
Patients who did and did not use immunosuppressant medications did not differ significantly in rates of COVID-19 infection.
Compared with patients who did not use corticosteroids, those who did use them had a higher chance of hospitalization, ventilator use, and death due to COVID-19 (all p<0.001). Compared with patients who did not use anti-TNF or aminosalicylate medications, those who used these medications had a lower chance of hospitalization (p<0.001). The other medication classes were not associated with study outcomes.
Limitations
Both study periods overlapped with the rollout of COVID-19 vaccinations, which may have affected COVID-19 infection and severity. Patients were not randomized to medication or not, therefore differences in outcomes may be due to underlying factors other than immunosuppressant use.
Conclusions and Relevance
Immunosuppressant medication use was not associated with a higher chance of COVID-19 infection. However, corticosteroid use was associated with higher rates of hospitalization, ventilator use, and death due to COVID-19, while use of anti-TNF and aminosalicylate medications was associated with lower rates of hospitalization.
| How this project fits under PCORI’s Research Priorities The research reported in this results summary was conducted using PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® is intended to improve the nation’s capacity to conduct health research, particularly comparative effectiveness research (CER), efficiently by creating a large, highly representative network for conducting clinical outcomes research. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute® (PCORI®). |
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 questioned the appropriateness of expressing study results in odds ratios, saying that these would be difficult to interpret in a cohort study looking at risk factors for severe COVID-19 and recommending that the researchers use risk ratios instead. The researchers explained that they wanted to maintain analyses in this report as they matched the analyses in their published outcomes paper. They did add a study limitation to the discussion indicating that some researchers would recommend risk ratios rather than odds ratios for this type of research.
- The reviewers noted that the report referenced COVID-19 complications related to corticosteroid use but these were not explained in the study methods. The researchers removed reference to COVID-19 complications since the study was really focused on assessing hospitalization, ventilation, and mortality.
Final Enhancement Report
This COVID-19 study's final enhancement report is expected to be available by November 2023.
Journal Citations
Results of This Project
Project Information
Key Dates
Study Registration Information
^Angela Dobes, MPH, was the original principal investigator of this study, and its original organization was the Crohn's & Colitis Foundation in New York.