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IBD TNF Inhibitors May Open Doors to SARS-CoV-2

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Infliximab (Remicade), a tumor necrosis factor (TNF) inhibitor, was associated with diminished serological response to SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD), a UK multicenter Research has revealed.

These reactions were further diminished in people who were also treated with immunomodulators, said Dr. Tariquafmad of the Royal Devon and Exeter NHS Foundation Trust in the United Kingdom.

Infliximab was independently associated with a lower serum positive rate compared to vedolizumab (Entyvio) (OR 0.66, 95% CI 0.51-0.87, P= 0.0027), combined with immunomodulators (OR 0.70, 95% CI 0.53-0.92, P= 0.012), they reported online Intestines..

In addition, patients with confirmed SARS-CoV-2 infection had seroconversion in patients treated with infliximab (39 of 81) compared to patients treated with vedrizumab (30 of 36). It was observed. P= 0.00044). In addition, the magnitude of anti-SARS-CoV-2 reactivity was low, with a median 0.8 cutoff index (0.2-5.6) vs. 37.0 (15.2-76.1). (P<0.0001).

Impaired serological response to SARS-CoV-2 can have significant implications for patients treated with public health and TNF inhibitors, so “considering serological testing and virus monitoring, Suboptimal vaccine responses, persistent infections, and viral evolution need to be detected and informed to public health policy, “Ahmad and the team wrote.

Intestinal selective anti-integrin α4β7 monoclonal antibody vedolizumab Vaccine reaction disorder Alternatively, increased susceptibility to systemic infections or diminished serological responses after vaccination with Streptococcus pneumoniae, influenza, viral hepatitis, or increased risk of serious respiratory infections.

The CLARITY IBD study analyzed the antibody response of 6,935 consecutive IBD patients aged 5 years and older recruited from 92 UK hospitals between 22 September and 23 December 2020. 4,685 were treated with infliximab and 2,250 were treated with vedolizumab.

Men accounted for about half of both groups. The average age was 37 years in the infliximab group and about 44 years in the vedolizumab group. Overall, 56.9% of patients had Crohn’s disease, 40.5% had ulcerative colitis, and 2.5% were unclassified.

At the time of recruitment, 56.3% of infliximab and 18.8% of vedolizumab patients were taking immunomodulators such as thiopurine and methotrexate.

The sandwich electrochemiluminescence immunoassay targeted a recombinant protein of the nucleocapsid antigen to identify antibodies against SARS-CoV-2.

Symptomatologically proven SARS-CoV-2 infection rates were similar between groups, but serum prevalence was as low as 3.4% in infliximab-treated patients and 6.0% in vedrizumab-treated patients (6%).P<0.0001).

Other studies show that the overall serum prevalence of anti-SARS-CoV-2 antibodies is 4.3%, adding evidence that IBD patients are at the same risk of SARS-CoV-2 infection as the general population. The study authors said.

In addition, only one-third of patients taking immunomodulators had detectable anti-SARS-CoV-2 antibodies. Seroconversion rates were 60% in patients treated with infliximab alone, but decreased to 37% in patients treated with infliximab and immunomodulators (infliximab and immunomodulators).P= 0.046). There was also a significant difference in the magnitude of anti-SARS-CoV-2 reactivity (P= 0.035).

The authors explained that infliximab may directly interfere with the immune mechanisms involved in the production of antibody responses. “This is biologically plausible because the pro-inflammatory effects of TNF include stimulation of B cell immunoglobulin synthesis, induction of germinal center formation, and co-stimulation of antigen-activated T cells. Maturation of antigen-presenting cells. “

Serre-Yu Wong, MD, PhD of Mount Sinai School of Medicine in New York City was asked for her views, pointed out a number of studies, and noted that IBD patients taking TNF inhibitors need to be carefully monitored. He said he suggested. ..

Her group recently conducted a single-center serological study of patients in the United States and found no difference between IBD patients with infliximab and IBD patients with vedolizumab. “But we didn’t look at the titers, which was different in that British researchers tested the receptor-binding domain of peplomers while testing the nucleocapsid antigen,” Wong said. Today’s MedPage. “This can make a big difference because there are differences in the neutralizing capacity and longevity of spikes and nucleocapsids. Data suggest that targeting spike proteins increases neutralizing capacity and longevity. And the vaccines currently in use in the United States target spikes. “

Regarding the interaction of infliximab with the new SARS-CoV-2 mutant, Wong said that, like other diseases, the recognition of mutant strains can be noticeably low.

Her group is currently planning to test antibodies against both nucleocapsid and spikes. “Because it’s the only way to distinguish between natural infections and vaccination,” she said.

Within the limits of some studies, the authors cited the fact that it is unclear whether diminished immune response in patients treated with infliximab leads to an increased risk of infection. In addition, this study only evaluated the humoral response to infection, and protective immunity may require further induction of memory T cell responses.

In addition, the patient-reported data in this study were affected by recall bias, which may underestimate the prevalence of possible COVID-19 symptoms.

Finally, the only TNF inhibitor investigated was infliximab, but the authors predict that important findings also apply to other anti-TNF monoclonal antibodies such as adalimumab, ertolizumab, and golimumab.

Disclosure

This study is F. Funded by Hoffmann La Roche, University of Hull Teaching Hospital NHS Trust, Biogen GmbH (Switzerland), Sertorion Healthcare, Galapagos NV, Royal Devon and Exeter NHS Foundation Trust.

Ahmad is F. Revealed financial relationships with Hoffmann La Roche, Biogen, Sertorion Healthcare and Galapagos NV. Support from Immundiagnostik during research. Prices from Biogen, Celltrion Healthcare, Immundiagnostik, Takeda, ARENA, Gilead Adcock Ingram Healthcare, Pfizer, and Genentech. Non-financial support from Tillotts other than the submitted work.

In addition to the studies submitted by multiple study co-authors, F. He has revealed many relationships with private companies such as Hoffmann La Roche, AbbVie, Gilead Sciences, Eli Lilly and Pfizer.

Wong had no competing interests to disclose regarding her comments.

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