IBD Therapies May Weaken COVID-19 Immune Response

James Alexander, PhD

New data suggests that some inflammatory bowel disease (IBD) therapies – such as anti-TNFs and JAK inhibitors – may attenuate COVID-19 vaccine-induced immune responses.

A team led by James Alexander, PhD, Imperial College London, conducted a multicenter prospective, case-control study of patients living with IBD. They sought to assess whether various immunosuppressive drug regimens affected or altered immunogenicity to COVID-19 vaccines.

“To our knowledge, this study is the first to systematically evaluate humoral immune responses to SARS-CoV-2 vaccination, both with mRNA and adenovirus vector vaccines, in patients receiving common immunosuppressives used in IBD,” Alexander and colleagues wrote.

Study Methods and Population

They recruited a total of 483 participants (all ≥18 years of age) across 9 hospitals in the UK. Of the cohort, 78 were treated with a thiopurine, 63 were treated with infliximab, 72 with a thiopurine plus infliximab, 57 with ustekinumab, 62 with vedolizumab, and 30 with tofacitinib.

The remaining 121 participants were healthy controls – or those with no “diagnosis of IBD and [who] were not currently being treated with systemic immunosuppressives for any other indication.” Furthermore, 370 patients had no evidence of previous infection with COVID-19.

All patients had received 2 doses of a COVID-19 vaccine (ChAdOx1 nCoV-19 [Oxford–AstraZeneca], BNT162b2 [Pfizer–BioNTech], or mRNA1273 [Moderna]). Doses were received 6-12 weeks apart.

The team used the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay to measure vaccine antibody responses 53–92 days following dose 2.Their primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in those who had not been previously infected with the virus.

Comparing the Data

Overall, they found that geometric mean spike protein antibody concentrations were significantly lower among patients treated with infliximab (156.8 U/mL [geometric SD, 5.7]; p<.0001), infliximab plus thiopurine (111.1 U/mL [5.7]; p<.0001), or tofacitinib (429.5 U/mL [3.1]; p = .0012) compared with the control group (1578.3 U/mL [3.7]).

However, the team observed no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019.8 U/mL [4.3]; p=.74), ustekinumab (582.4 U/mL [4.6]; p=0.11), or vedolizumab (954.0 U/mL [4.1]; p = .50) and the healthy controls.

Multivariable modeling showed independently an association between lower anti-SARS-CoV-2 spike protein antibody concentrations and infliximab (geometric mean ratio 0.12, 95% CI 0.08 – 0.17; p<.0001) as well as tofacitinib (0.43, 0.23 – 0·81; p = .0095). This was not the case with ustekinumab (0.69, 0.41 – 1.19; p = .18), thiopurines (0.89, 0.64 – 1.24; p =.50), or vedolizumab (1.16, 0.74 – 1.83; p = .51).

Compared with adenovirus virus vector vaccines, mRNA vaccines (3.68, 2.80 – 4.84; p<.0001) were independently associated with higher antibody concentrations.

And finally, older age per decade (0.79, 0.72 – 0·87; p<.0001) was linked with lower antibody concentrations.

“In the absence of previous infection, 10% of patients on infliximab monotherapy, 13% on thiopurine plus infliximab combination therapy, and 4% on ustekinumab did not generate protective antibody responses,” investigators wrote.

In light of these findings, they stressed the importance of personalized treatment, booster doses, and the prioritization of patients receiving anti-TNFs and tofacitinib.

“The increased magnitude of response elicited by mRNA versus adenovirus vaccines indicates that strategies using full-dose mRNA vaccines might be favoured in these patient groups,” they concluded.

The study "COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study" was published in The Lancet Gastroenterolgy & Hepatology.