COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study

James L Alexander, Zhigang Liu, Diana Muñoz sandoval, Catherine Reynolds, Hajir Ibraheim, Sulak Anandabaskaran, Aamir Saifuddin, Rocio Castro seoane, Nikhil Anand, Rachel Nice, Claire Bewshea, Andrea D'mello, Laura Constable, Gareth R Jones, Sharmili Balarajah, Francesca Fiorentino, Shaji Sebastian, Peter M Irving, Lucy C Hicks, Horace R T WilliamsAlexandra J Kent, Rachel Linger, Miles Parkes, Klaartje Kok, Kamal V Patel, Julian P Teare, Daniel M Altmann, James R Goodhand, Ailsa L Hart, Charlie W Lees, Rosemary J Boyton, Nicholas A Kennedy, Tariq Ahmad, Nick Powell, Ijeoma Chukwurah, Sulaimaan Haq, Parita Shah, Stephanie Wilken-Smith, Anitha Ramanathan, Mikin Patel, Lidia Romanczuk, Rebecca King, Jason Domingo, Djamila Shamtally, Vivien Mendoza, Joanne Sanchez, Hannah Stark, Bridget Knight, Louise Bee, Charmaine Estember, Anna Barnes, Darcy Watkins, Sam Stone, John Kirkwood, Marian Parkinson, Helen Gardner-Thorpe, Kate Covil, Lauranne Derikx, Beatriz Gros alcalde, Irish Lee, Bessie Cipriano, Giuseppe Ruocco, Manisha Baden, Graham Cooke, Katrina Pollock, Evgenia Kourampa, Ciro Pasquale, Elena Robisco-Diaz, Suhaylah Bhatti

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Background
COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose.

Methods
VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28–49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data.

Findings
Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p
Interpretation
A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors.

Funding
Pfizer.
Original languageEnglish
Pages (from-to)1005-1015
JournalThe Lancet Gastroenterology & Hepatology
Volume7
Issue number11
Early online date9 Sept 2022
DOIs
Publication statusPublished - 1 Nov 2022

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