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COVID-19 Resource Center

Disclosures: Ahmad reports CLARITY IBD is an investigator-led, UK National Institute for Health Research COVID-19 urgent public health study funded by the Royal Devon and Exeter NHS Foundation Trust, Hull University Teaching Hospital NHS Trust and by unrestricted educational grants from F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), Takeda (UK) and Galapagos NV (Belgium).
May 05, 2021
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Q&A: Remicade treatment weakens COVID-19 antibody response in IBD

Disclosures: Ahmad reports CLARITY IBD is an investigator-led, UK National Institute for Health Research COVID-19 urgent public health study funded by the Royal Devon and Exeter NHS Foundation Trust, Hull University Teaching Hospital NHS Trust and by unrestricted educational grants from F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), Takeda (UK) and Galapagos NV (Belgium).
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Patients who received Remicade for inflammatory bowel disease had weakened anti-COVID-19 antibody responses following a single vaccination dose, according to research published in Gut.

In a prospective, observational cohort study, researchers compared antibody responses and seroconversion rates in Remicade-treated (infliximab, Janssen) patients (n = 856) vs. Entyvio-treated (vedolizumab, Takeda) patients (n = 428) 3-weeks to 10-weeks after receiving a single dose of a SARS-CoV-2 vaccine.

“We recommend that patients with IBD accept whichever approved SARS-CoV-2 vaccination is offered to them. Several countries have adopted a strategy of delaying the second vaccine dose. However, delayed second dosing may leave patients treated with anti-TNF drugs at risk for infection after a single dose and patients should consider that they might not be protected from SARS-CoV-2 infection.”

According to study results, patients treated with infliximab had lower anti-SARS-CoV-2 antibody concentrations following a BNT162b2 dose (6 U/mL vs. 28.8 U/mL) as well as a ChAdOx1 nCoV-19 dose (4.7 U/mL vs. 13.8 U/mL). Multivariable analysis also yielded lower antibody concentrations for infliximab-treated patients compared with vedolizumab-treated patients following the BNT162b2 vaccine (fold change [FC] = 0.29; 95% CI, 0.21-0.4) and the ChAdOx1 nCoV-19 vaccine (FC = 0.39; 95% CI, 0.3-0.51). Researchers noted higher seroconversion rates in patients with prior SARS-CoV-2 infection after a single dose of either vaccine as well as in patients who received two doses of the BNT162b2 vaccine.

Healio Gastroenterology spoke with Tariq Ahmad, D.Phil, MB, ChB, FRCP, consultant gastroenterologist at Royal Devon and Exeter Hospital and honorary associate professor at the University of Exeter, about the important take-home messages and how these results inform IBD management going forward.

Tariq Ahmad

Healio: Why did your team undertake this study?

Ahmad: During the early months of the COVID-19 pandemic there was considerable concern that biologic and immunomodulator drugs used in the treatment of IBD might increase the risk for and severity of COVID-19 and impair the protective immune responses that usually follow infection or vaccination. With a lack of evidence to inform public health policy, the U.K. government advised patients treated with these drugs to follow strict social distancing measures, including shielding.

We established the CLARITY IBD study to define the impact of these drugs on COVID-19 infection and immunity. Previous studies had reported that anti-TNF drugs (including infliximab) increase the risk for serious respiratory infections and impair protective immunity following certain vaccinations. Therefore, we hypothesized that anti-SARS-CoV-2 antibody responses would be impaired following SARS-CoV-2 infection and vaccination in patients treated with infliximab. To test this hypothesis, we compared antibody responses in patients with IBD treated with infliximab with a reference cohort treated with vedolizumab, a gut-selective anti-integrin alpha-4-beta-7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections.

Healio: What are the most important take-home message?

Ahmad: In our first paper we reported that rates of SARS-CoV-2 infection were similar between infliximab-treated and vedolizumab-treated patients with IBD suggesting that infliximab does not increase the risk for infection. However, infliximab-treated patients were less likely to have a positive antibody test, both in the overall patient group and in patients with a confirmed infection based on standard tests. Rates of positive antibody tests were lowest in participants who were also taking other immunosuppressants, such as azathioprine, mercaptopurine or methotrexate alongside infliximab. These data raised the possibility that anti-TNF treated patients might be at risk for impaired vaccine responses.

In our second paper we confirmed that anti-SARS-CoV-2 spike antibody concentrations and rates of seroconversion are lower following a single dose of both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines in infliximab compared with vedolizumab-treated patients. Reassuringly however, antibody concentrations and seroconversion rates were higher in patients with past SARS-CoV-2 infection and after two vaccine doses.

Healio: How do these results inform IBD management in patients who receive the COVID-19 vaccine going forward?

Ahmad: We recommend that patients with IBD accept whichever approved SARS-CoV-2 vaccination is offered to them.

Several countries have adopted a strategy of delaying the second vaccine dose to allow a lower level of protective immunity across a greater proportion of the population. The U.K. has demonstrated the success of this strategy in reducing transmission and the number of SARS-CoV-2 infections. However, delayed second dosing may leave patients treated with anti-TNF drugs at risk for infection after a single dose and patients should consider that they might not be protected from SARS-CoV-2 infection.

We strongly encourage patients to continue anti-TNF treatment for three reasons. First, data from this and other studies suggest that these drugs do not put patients at an increased risk for SARS-CoV-2 infection. Next, there may be benefits of anti-TNF therapy reducing the severe inflammation that characterizes severe COVID-19 disease. And finally, protective antibody responses are observed for most patients after vaccine doses.

Even after two antigen exposures, a small subset of patients failed to mount an antibody response. While other parts of the immune system, including T-cell responses, may provide protection against SARS-CoV-2 infection, antibody testing and additional booster doses of vaccine should be considered to protect these at-risk patients.

Healio: What is the next step in future research?

Ahmad: We are continuing to follow the CLARITY IBD cohort of 7,000 participants. We are currently examining antibody levels and seroconversion rates following a second SARS-CoV-2 vaccine dose and will explore durability of antibody responses and vaccine effectiveness over the 40-week follow-up period. We aim to publish our data on antigen-specific T-cell responses after first and second doses of SARS-CoV-2 vaccination in 2-months.