For people with inflammatory bowel disease (IBD) taking immunosuppressive medication, a third dose of a COVID-19 mRNA vaccine significantly increases neutralizing antibodies against the original SARS-CoV-2 strain, but the picture is more complicated for protection against the Omicron variant, according to a research letter published in Gastroenterology.
“As further mutations in the viral genome accumulate over time, with the attendant risk of immune evasion, it remains important to continue to reappraise vaccination strategy, including the implementation of personalized approaches for some patients, such as those treated with anti-TNF drugs and JAK inhibitors,” wrote Zhigang Liu, PhD, a research associate in the department of metabolism, digestion, and reproduction at Imperial College London, and his colleagues. “Preferential use of bivalent vaccines may be especially valuable in IBD patients taking anti-TNF agents or JAK inhibitors,” they wrote. Their study did not assess neutralizing antibodies resulting from use of the bivalent vaccine, however.
The researchers tracked 268 participants, including 49 healthy participants serving as controls, from May 2021 through March 2022. The other participants had IBD and included 51 patients taking thiopurines, 36 patients taking infliximab, 39 taking both infliximab and thiopurines, 39 taking ustekinumab, 38 taking vedolizumab, and 16 taking tofacitinib. The IBD patients were all enrolled in the SARS-CoV-2 Vaccination Immunogenicity in Immunosuppressed Inflammatory Bowel Disease Patients (VIP) cohort.
None of the participants had evidence of a SARS-CoV-2 infection at baseline. All had received two doses of an mRNA COVID-19 vaccine (all received Pfizer, except two controls who received Moderna) or two doses of the AstraZeneca vaccine as their primary vaccination. All received an mRNA vaccine for their third dose. Among the IBD patients, 137 received the AstraZeneca in their primary two-dose series, and 82 received Pfizer.
First the researchers assessed the participants’ humoral response to the vaccine against the original SARS-CoV-2 strain and against the Omicron BA.1 variant. Neutralizing antibody titers rose significantly against both strains after the third vaccine dose for all participants.
“However, 50% neutralization titer (NT50) values were significantly lower against Omicron than against the ancestral strain in all study groups, irrespective of the immunosuppressive treatment regimen,” the authors reported. NT50 values are a measure that reflect a vaccine-induced humoral immunity against SARS-CoV-2 after vaccination.
Compared to the healthy controls, individuals receiving infliximab, tofacitinib, or infliximab/thiopurine combination therapy showed significantly lower responses after the second and third vaccine doses. Thirteen patients did not generate NT50 against Omicron after the second vaccine dose, and 7 of them were on infliximab monotherapy. They represented nearly 20% of all infliximab monotherapy participants.
Next the researchers assessed the risk of a breakthrough infection according to neutralizing titer thresholds. Individuals with an NT50 less than 500 had 1.6 times greater odds of a breakthrough infection than those with an NT50 above 500, they noted. After two vaccine doses, 46% of participants with IBD had an NT50 above 500 for the ancestral strain, which rose to 85% of those with IBD after a third dose.
In the healthy control group, 35% had an NT50 under 500 after two doses, and 14% of them had a breakthrough infection, all of which were mild and none of which required hospitalization. The NT50 in healthy controls, however, was not significantly associated with risk of breakthrough infection.
“In this study, neutralizing titers elicited against the omicron variant were generally poor for all individuals and were substantially lower in recipients of infliximab, infliximab/thiopurine combination, or tofacitinib therapy,” the authors concluded. “This raises concerns about whether currently available vaccines will be sufficient to protect against continually evolving SARS-CoV-2 variants, especially in patients established on certain immunosuppressive drugs.”
The small population sizes for each subgroup based on medication was one of the study’s limitations. Another was the fact that it was underpowered to conclusively determine whether an increased risk of breakthrough infection exists in IBD patients who have lower titers of neutralizing antibodies. A limitation for generalization to U.S. patients is that just 64% of the IBD patients received the AstraZeneca vaccine, which is not offered in the United States, for their first two doses before receiving the third mRNA (Pfizer) dose.
The study was funded by Pfizer in an independent research grant and by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge, and the NIHR Clinical Research Facility Cambridge.
Dr. Liu and one other author had no disclosures. The other 18 authors have a range of disclosures related to various pharmaceutical companies, including Pfizer.