Findings inform clinical practice and public health
The study is very important for many reasons, said Kim L. Isaacs, MD, PhD, AGAF, of the University of North Carolina at Chapel Hill in an interview. “It is known that there is decreased responsiveness to a number of routine vaccinations in IBD patients on immune active therapy. In terms of SARS-CoV-2, development of an immune response with infection is important in terms of severity of infection, reinfection, and possibly limiting spread of infection in this patient population,” she said. “Looking at both serum seroconversion and reactivity of immune response in patients with known SARS-CoV-2 infection will help to define clinical and public health guidance, and also may be predictive as to what might happen with SARS-CoV-2 immunization based on background biologic or immunosuppressant therapy,” she noted.
Dr. Isaacs said that she was not surprised by the study findings. “Anti-TNF, thiopurine, and methotrexate therapy are all thought to be systemically active and likely to suppress the immune response to infection and vaccination,” she said. Vedolizumab, on the other hand, is thought to be less systemically active and clinically is associated with fewer serious infections.
Data will drive patient counseling
“These results affect counseling of IBD patients on immune active therapy who have had a SARS-CoV-2 infection,” said Dr. Isaacs. “They should be made aware that infection does not indicate protection for further infection. Although the issues that are raised in this study are of concern, patients should not have clinically beneficial therapy discontinued or switched based on these results,” she said.
“Additional research is needed to determine what the seroconversion rate is with the currently available immunizations for SARS-CoV-2,” said Dr. Isaacs. More questions to address include whether there are differences in the different products available, whether immunization after SARS-CoV-2 infection improves both seroconversion and immune reactivity, and whether there is any benefit to transiently stopping dual immune active therapy during the time of immunization, she said.
Further studies can fill knowledge gaps
“There is a knowledge gap in our understanding of susceptibility to SARS-CoV-2 infections among patients with IBD who have previously been infected,” Shirley Cohen-Mekelburg, MD, MS, staff physician and research scientist in the inflammatory bowel disease program at the Veterans Affairs Ann Arbor (Mich.) Healthcare System, said in an interview. ”This is a first step in beginning to narrow this gap – to provide patients and providers with data to drive recommendations during this COVID-19 pandemic.”
She added that, while further work needs to be done, the study findings do support potential benefit for ongoing vigilance among patients receiving infliximab for IBD. “The study findings also drive us to seek answers to more questions: For example, should we consider serological testing for patients on infliximab? How does the presence or absence of anti–SARS-CoV-2 antibodies associate with susceptibility to infection for patients with infliximab?
“Further studies examining anti–SARS-CoV-2 reactivity are necessary to better understand antibody responses between patients with IBD to the general population, or between patients on immunosuppressive therapy and the general population,” she said. “Observational studies are also not designed to examine the causal relationship between infections, medications, and antibody responses. There may be some inherent differences to patients who receive infliximab as compared to vedolizumab for IBD.”
The study was supported by Biogen (Switzerland), Celltrion Healthcare, Galapagos, F. Hoffmann-La Roche, Hull University Teaching Hospital NHS Trust, and the Royal Devon and Exeter NHS Foundation Trust. The study authors disclosed financial and nonfinancial relationships with numerous companies, including AbbVie, Biogen, Celltrion Healthcare, Galapagos, F. Hoffmann-La Roche, and Immundiagnostik, as well as Janssen, who markets infliximab, and Takeda, who markets vedolizumab. Dr. Isaacs and Dr. Cohen-Mekelburg had no relevant financial conflicts to disclose.
This article was updated 3/31/21.