Infliximab Neutralizes COVID-19 Vaccine Antibodies More Than Vedolizumab in IBD

Adopting bivalent or variant-specific vaccination strategies might be especially valuable in patients treated with infliximab.

Patients with inflammatory bowel disease (IBD) treated with infliximab demonstrate higher likelihood of neutralized antibody responses following COVID-19 vaccination and increased risk for breakthrough COVID-19 infection than patients treated with vedolizumab, according to study findings published in The Lancet Gastroenterology & Hepatology.

Researchers conducted a prospective, multicenter, observational cohort study (CLARITY IBD) from September 22, 2020, to December 23, 2020, across 92 hospitals in the United Kingdom. Of the 7224 patients identified with IBD, the researchers only enrolled 1288 patients (52.1% men) without a history of COVID-19 infection who received uninterrupted biological therapy during the 6-week study period.

The researchers evaluated the effects infliximab (n=871) and vedolizumab (n=417) had on neutralizing antibody responses following 3 COVID-19 vaccine doses against the wild-type and Omicron BA.1 and BA.4/5 variants. They also analyzed the incidence of breakthrough COVID-19 infections and their relationship to neutralizing antibody titers.

Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines…

In patients who had received 3 doses of the COVID-19 vaccine, average 50% neutralizing antibody titers (NT50s) were significantly lower among the patients treated with infliximab compared with vedolizumab across all 3 studied variants:

  • Mean titers for wild-type (infliximab, 2062; 95% CI, 1720-2473 vs vedolizumab, 3440; 95% CI, 2939-4026; P <.0001);
  • Mean titers for BA.1 variant (infliximab, 107.3; 95% CI, 86.40-133.2 vs vedolizumab, 648.9; 95% CI, 523.5-804.5; P <.0001); and
  • Mean titers for BA.4/5 variants (infliximab, 40.63; 95% CI, 31.99-51.60 vs vedolizumab, 223.0; 95% CI, 183.1-271.4; P <.0001).

Correspondingly, incidence of breakthrough COVID-19 infections was higher among patients treated with infliximab (n=119, 13.7%; 95% CI, 11.5-16.2%) compared with those receiving vedolizumab (n=29, 7%; 4.8-10%; P =.00040).

After further analysis, treatment of IBD with infliximab was associated with a higher hazard risk after the third vaccine dose against COVID-19 compared with vedolizumab (hazard ratio [HR], 1.71; 95% CI, 1.08-2.71; P =.022). When comparing risk for infection based on variant type, the researchers found that neutralizing antibody titers from the vaccines were higher against the BA.4/5 variant, resulting in significantly lower hazard risk and longer time to breakthrough infections (HR, 0.87; 95% CI, 0.79-0.95; P =.0028).

Limitations of the study include a lack of assessment of T-cell immune responses against COVID-19, lack of comparison with healthy controls, and a comparison of only 2 IBD biological therapies.

The study authors conclude, “Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies.”

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.

References:

Liu Z, Le K, Zhou X, et al. Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study. Lancet Gastroenterol Hepatol. Published online December 5, 2022:S2468-1253(22)00389-2. doi:10.1016/S2468-1253(22)00389-2