Infliximab Weakens COVID-19 Antibody Response for Patients With IBD

Heidi Splete

March 25, 2021

Patients treated with infliximab for inflammatory bowel disease (IBD) showed significantly reduced response to COVID-19 antibodies, compared with those treated with vedolizumab, according to data from nearly 7,000 patients.

Although anti-tumor necrosis factor (anti-TNF) drugs are routinely used for patients with IBD, the impact of their immune-suppressing properties on protective immunity to COVID-19 is unknown, wrote Nicholas A. Kennedy, MD, of the University of Exeter (England) and colleagues. These drugs have been reported to impair protective immunity following vaccines for other diseases, such as those for influenza and viral hepatitis.

"By suppressing immune responses, biological and immunosuppression therapies may lead to chronic SARS-CoV-2 infection and have recently been implicated in the evolution and emergence of novel variants," they noted, citing a study published in Cell.

In the current study, published in Gut, the researchers used data from the CLARITY IBD study to identify 6,935 patients with IBD aged 5 years and older seen at 92 hospitals in the United Kingdom between Sept. 22, 2020, and Dec. 23, 2020. Of these, 4,685 were treated with infliximab, and 2,250 received vedolizumab. The proportion of study participants with a positive anti–SARS-CoV-2 antibody test was the primary outcome, with secondary outcomes including proportion with positive antibodies following positive polymerase chain reaction test for SARS-CoV-2 and the magnitude of antibody reactivity.

Substantial Seroprevalence Differences

Overall, rates of symptomatic and proven SARS-CoV-2 infection and hospitalization were similar between infliximab-treated and vedolizumab-treated patients with IBD. However, seroprevalence was significantly lower in the infliximab group, compared with the vedolizumab group (3.4% vs. 6.0%; P < .0001). In addition, infliximab and immunomodulator use were each independently associated with lower seropositivity, compared with vedolizumab (odds ratio, 0.66 for infliximab and OR, 0.70 for immunomodulators) in a multivariate analysis.

In a sensitivity analysis, 39 of 81 infliximab-treated patients with polymerase chain reaction-confirmed COVID-19 infection seroconverted (48%), compared with 30 of 36 vedolizumab-treated patients (83%) (P < .00044). Infliximab-treated patients with confirmed infections also showed a lower magnitude of anti–SARS-CoV-2 reactivity, compared with vedolizumab-treated patients (P < .0001).

From a clinical perspective, the lower seroconversion rates and reduced levels of anti–SARS-CoV-2 antibody reactivity might increase susceptibility to recurrent COVID-19 infections in infliximab-treated IBD patients, the researchers noted. In addition, the impaired serological responses might promote chronic nasopharyngeal colonization and consequently promote the development of COVID-19 variants and drive persistent transmission, the researchers said.

The study findings were limited by several factors including lack of knowledge on the impact of attenuated immune response on infection risk, the potential for recall bias associated with patient reports, and the focus on infliximab only, the researchers pointed out. However, the key findings are likely apply to other anti-TNF monoclonal antibodies including adalimumab, certolizumab and golimumab, they suggested.

The study was strengthened by the recruitment of a large number of patients in a narrow time frame and comprehensive collection of data on patient-reported outcomes, COVID-19 testing, and serological assay results, the researchers said. Overall, the findings support the public health value of serological testing and virus surveillance to identify suboptimal vaccine response and to consider implications for practice, they added. "If attenuated serological responses following vaccination are also observed, then modified immunization strategies will need to be designed for millions of patients worldwide," they emphasized.

Findings Inform Clinical Practice and Public Health

Dr Kim Isaacs

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.

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 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 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, staff physician and research scientist in the inflammatory bowel disease program at the Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, 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. Isaacs and Cohen-Mekelburg have disclosed no relevant financial relationships.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....