Breakthrough Infections More Likely in Infliximab Treated IBD Patients Than Those Treated With Vedolizumab

Zhigang Liu, PhD

Patients with inflammatory bowel disease (IBD) treated with infliximab who were vaccinated against SARS-CoV-2 were more likely to have a breakthrough infection than patients treated with vedolizumab, but the benefits of the vaccine are still superior.

A team, led by Zhigang Liu, PhD, Department of Metabolism, Digestion and Reproduction, Imperial College London, determined how infliximab and vedolizumab affect vaccine-induced neutralizing antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants.

The Treatments

Anti-TNF drugs, including infliximab, are linked to attenuated antibody responses following SARS-CoV-2 vaccination. The variants included in the analysis have the ability to evade host immunity and with emerging sublineages are currently the dominating variants causing the current waves of infection.

In the prospective, multicenter, observation, CLARITY IBD cohort study, the investigators looked at the effect of infliximab and vedolizumab on SARS-CoV-2 infections and vaccinations in patients with IBD.

The study included patients aged 5 years or older with an IBD diagnosis that were treated with infliximab or vedolizumab for 6 weeks or longer in infusion units at 92 hospitals in the UK. Each participant had uninterrupted biological therapy since recruitment and were not previously diagnosed with a SARS-CoV-2 infection.

Outcomes

The investigators sought primary outcomes of neutralizing antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 following 3 doses of a SARS-CoV-2 vaccine.

The team also investigated the risk of breakthrough infections in relation to neutralizing antibody titers using Cox proportional hazard models.

There were 7224 patients with IBD recruited to the study between September 22 and December 23, 2020. Of this group, 1288 had no previous SARS-CoV-2 infections after 3 doses of the vaccine that were established on either infliximab (n = 871) or vedolizumab (n = 417). The median age of the patient population was 46.1 years.

Following 3 doses of SARS-CoV-2 vaccine, 50% neutralizing titers were significantly lower in the infliximab group compared to patients treated with vedolizumab against wild-type (geometric mean, 2062; 95% CI, 1720–2473 vs geometric mean, 3440; 95% CI, 2939–4026; P <0.0001), BA.1 (geographic mean, 107.3; 95% CI, 86.40–133.2 vs geographic mean, 648.9; 95% CI, 523.5–804.5; P <0.0001), and BA.4/5 (geographic mean, 40.63; 95% CI, 31.99–51.60] vs geographic mean, 223.0; 95% CI, 183.1–271.4; P <0.0001) variants.

Breakthrough infections more frequently occurred in patients treated with infliximab (n = 119; 13.7%; 95% CI, 11.5–16.2) than in those treated with vedolizumab (n = 29; 7.0%; 95% CI, 4.8–10.0; P = 0.00040).

The Cox proportional hazard models show time to breakthrough infection after the third vaccine dose in the infliximab group was associated with a higher hazard risk than treatment with vedolizumab (HR, 1.71; 95% CI, 1.08-2.71; P = 0.022).

There was also higher neutralizing antibody titers against BA.4/5 with a lower hazard risk in the group with a breakthrough infection and a longer time to breakthrough infection (HR, 0.87; 95% CI, 0.79-0.95; P = 0.0028).

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

The study, “Neutralizing 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 multicenter cohort study,” was published online in The Lancet Gastroenterology & Hepatology.