乌鸦传媒

In patients with inflammatory bowel disease (IBD), treatment with infliximab (Remicade) was associated with attenuated immunogenicity to a single dose of either the Pfizer or AstraZeneca COVID-19 vaccine, a large British cohort study found.

Concurrent use of an immunomodulator with infliximab, a tumor necrosis factor (TNF) inhibitor, further reduced immunogenicity to either vaccine, reported Tariq Ahmad, MD, of the Royal Devon and Exeter National Health Service (NHS) Foundation Trust in England, and colleagues.

"Delayed second dosing should be avoided in patients treated with infliximab," the researchers wrote in .

Reassuringly, however, vaccination after SARS-CoV-2 infection or after a second dose of vaccine, led to seroconversion in most IBD patients.

The investigators re-examined a cohort of English and Scottish IBD patients from the CLARITY IBD (Impact of Biologic Therapy on SARS-CoV-2 Infection and Immunity) study. Their original analysis showed similarly reduced immunogenicity to SARS-CoV-2 infection in the infliximab-treated group, with these patients having a weaker antibody response. The vedolizumab-treated group exhibited no such reduction.

Adding an immunomodulator to vedolizumab has not been shown to impair immunogenicity in research conducted before the COVID-19 pandemic.

The current study involved 1,293 IBD patients who received either the Pfizer/BioNTech BNT162b2 mRNA vaccine (45.6%) or Oxford/AstraZeneca's ChAdOx1 nCoV-19 adenovirus-vector vaccine (54.4%). Average age was 44 years, a little more than half were male, and 91% were white. Most were treated with infliximab (69%), with a third receiving the gut-selective anti-integrin α4β7 antibody vedolizumab (Entyvio). Spike antibodies were measured 3 to 10 weeks after their initial dose.

The lowest rates of seroconversion (defined as an anti-SARS-CoV-2 spike antibody concentration ≥15 U/mL) occurred in participants treated with infliximab in combination with an immunomodulator (27.1% with Pfizer vaccine, 20.2% with AstraZeneca's), whereas the highest rates were seen in patients on vedolizumab monotherapy (74.7% and 57.3%, respectively).

Older age, Crohn's disease (vs ulcerative colitis or unclassified IBD), and current smoking were similarly associated with lower anti-SARS-CoV-2 antibody concentrations, irrespective of vaccine type. Non-white ethnicity was associated with higher antibody concentrations following a single dose of either vaccine.

"Poor antibody responses to a single dose of vaccine unnecessarily exposes infliximab-treated patients to SARS-CoV- 2 infection," the authors wrote. "However, because we observed higher rates of seroconversion in patients with two exposures to SARS-CoV-2 antigen, even in the presence of TNF blockade, these patients should be prioritised for optimally timed second doses."

Until their second dose, these patients should consider themselves unprotected and continue to practice enhanced physical distancing and shielding, the authors noted.

With the continuing surge of the pandemic, some countries -- such as England -- have postponed giving second doses in order to confer some immunity on a larger group of people, thereby trading greater effectiveness for protection, albeit lower, across more at-risk populations. The U.S. has kept to the recommended two-shot schedule with its authorized Pfizer and Moderna mRNA vaccines, but a .

Serre-Yu Wong, MD, PhD, of Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the British analysis, pointed to studies from her institution on various biological therapies -- including infliximab -- after a second dose of either mRNA vaccine. And IBD patients with previous SARS-CoV-2 seroconversion exhibited high index values after a single dose of either vaccine.

"But it's important to remember that it's one thing to measure the number of antibodies and a different thing to know what amount is protective and for how long," Wong told 乌鸦传媒. "It will take time to generate data on those questions."

The take-home message from CLARITY IBD is that all patients should receive their COVID-19 vaccine on schedule without delay, especially those patients on medications such as infliximab, according to Miguel Regueiro, MD, of the Cleveland Clinic in Ohio.

"At a time in which some people are hesitant to receive the COVID vaccine or are delaying a second dose of the vaccine, this study elucidates the successful immunogenicity to two shots of the vaccine," he told 乌鸦传媒.

In his practice, Regueiro recommends that all IBD patients, independent of medication or immunosuppressed status, be vaccinated and not delay their second dose.

The authors called for further observational studies to determine the impact of other classes of therapies for immune-mediated inflammatory diseases on SARS-CoV-2 vaccine immunogenicity.

They cited several limitations to their study, including the use of an electrochemiluminescence immunoassay to measure antibody concentrations rather than a "more biologically relevant" neutralizing assay. In addition, the study only assessed humoral responses to infection, and it is likely that protective immunity additionally requires the induction of memory T-cell responses.

In another limitation, it could not investigate whether the timing of biological infusion with respect to vaccination or drug level at the time of vaccination influenced antibody responses. Finally, the study was limited to a single anti-TNF agent. The authors expect, however, that their key findings will apply to other anti-TNF biologics.

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