Update on COVID-19 and IBD

Anti-tumor necrosis factor (TNF) medications do not appear to be associated with severe outcomes from infection with the SARS-CoV2-2019 virus, but more data are needed to further understand the impact of other drug classes on the outcomes of patients with inflammatory bowel disease (IBD) who become infected with the virus that causes COVID-19, according to Erica Brenner, MD.

Dr Brenner is a pediatric gastroenterology fellow at the University of North Carolina at Chapel Hill, where the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) Registry was developed. Dr Brenner was involved in creating the registry along with Michael D. Kappelman, MD, MPH, who is an associate professor in the Division of Pediatric Gastroenterology at the University of North Carolina; Ryan Ungaro, MD, who is an assistant professor of gastroenterology at the Icahn School of Medicine at Mt. Sinai in New York; Jean-Frederic Colombel, MD, who is a professor of gastroenterology at the Icahn School of Medicine at Mt. Sinai in New York; and Manasi Agrawal, MD, who is an instructor from the Icahn School of Medicine at Mt. Sinai in New York.

Almost 80% of patients with severe COVID-19 requiring intensive care have at least one underlying comorbidity, Dr Brenner explained at the virtual Advances in Inflammatory Bowel Disease (AIBD) regional meeting on September 12. Because patients with IBD frequently are treated with immunosuppressive treatments that increase the risk of infection, gastroenterologists were concerned about the possible risks to their patients resulting from the spread of the pandemic. “We needed more data regarding the disease course of COVID-19 in patients with IBD, including the impacts of clinical characteristics and medications,” she said.

The SECURE-IBD Registry was created to help define the impact of COVID-19 on patients with IBD and to evaluate associations among age, comorbidities, disease characteristics, and IBD treatments with the outcomes of those patients who contracted COVID-19.

Health care providers around the world were invited to report on a web-based platform cases of their patients with IBD who developed COVID-19. The registry requires that these reports be made a minimum of 7 days from the onset of symptoms and after sufficient time has passed to observe the disease course through resolution of acute illness or death.

The data collected include patient demographics, IBD type, comorbidities, disease activity (by physician global assessment), body mass index, smoking, and IBD medications at time of COVID-19 infection. They also include the outcomes of COVID-19, including whether the patients required hospitalization, admission to an intensive care unit (ICU), use of a ventilator, and whether the patient recovered or died.

As of August 25, the SECURE-IBD Registry has had 2156 cases reported from 56 different countries and 46 states in the United States, Dr Brenner said. Of those cases, 48% are women;

55% of patients are in remission; 19% have mild disease; 21% have moderate to severe disease; and in 4%, the disease status is unknown. A total of 7% of these cases required intensive care and/or ventilation; 3% resulted in the patient’s death. The highest number of cases was seen in patients aged 30 to 39 years (n=453); there were 3 deaths among these patients (1%) and a 3% rate of ICU care and/or ventilation required. The highest death toll was among patients aged older than 80 years (25%). The majority of patients reported had no comorbidities; among patients with 3 or more comorbidities, the death rate was 21%, compared with no deaths, among patients without comorbidities. 

Results of a comparison of outcomes by medication for the entire cohort on the SECURE-IBD registry showed that patients on anti-TNF monotherapy, interleukin (IL)-12/23 inhibitors, or anti-TNFs combined with 6-mercaptopurine, azathioprine, or methotrexate had a death rate of 1%. However, the risk of requiring ICU care and/or ventilation was lower (2%) for anti-TNF monotherapy than for IL-12/23 inhibitors (3%) or combination therapy (6%).

The highest risks of hospitalization, requiring ICU care and/or ventilation, and of death were found among patients taking oral or parenteral corticosteroids, Dr Brenner noted. Of the 161 patients in the registry using steroid therapy, 31 (19%) required ICU care and/or ventilation, and 14 (9%) died.

Dr Brenner explained that a subanalysis comparing the effects of 5-ASA/sulfasalazine with TNF antagonists found that treatment with 5-ASA/sulfasalazine was associated with increased odds of hospitalization or death, after controlling for a variety of factors including type of IBD, disease activity, smoking, and number of comorbidities. In addition, a similar comparison found that combination therapy with an anti-TNF agent and another therapeutic was also associated with a higher risk of hospitalization or death than the use of an anti-TNF agent alone.

“We don’t yet understand the potential mechanisms underlying these findings,” she said. “Might 5-ASA be harmful, or are other biologics helpful? Is there a reporting bias at work? We need more data to understand what might be driving these results.”

The primary strengths of the SECURE-IBD Registry are “a robust, worldwide collaboration; a large, geographically diverse sample of pediatric and adult patients with IBD; and reporting directly by physicians and trained staff,” Dr Brenner stated. However, there are limitations as well, she said. “The registry is a convenience sample that only includes confirmed cases. There is a risk of reporting bias. The registry may have an overrepresentation of severe cases, and those from areas with readily available testing, it may underrepresent severely ill patients hospitalized at an outside hospital or those who die without the knowledge of their gastroenterologist.”

The key findings to date from SECURE-IBD, Dr Brenner stated, are: “Increasing age, comorbidities, and corticosteroids are associated with the most severe COVID-19 outcomes. More data are needed to further understand signals in other drug classes, such 5-ASA and TNF antagonist combination therapy. However, anti-TNF agents do not appear to be associated with increased risks of severe outcomes for patients with IBD who contract COVID-19.”

Dr Brenner encouraged the attendees to visit the SECURE-IBD website at www.covidibd.org and report a case by filling out a case report form, and to access the site’s data, which is updated weekly.

—Rebecca Mashaw

Reference:

Brenner, EJ. Update on COVID-19 and IBD: The SECURE-IBD Registry. Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; September 12, 2020; virtual.