J Crohns Colitis. 2024 Apr 23;18(4):560-569. doi: 10.1093/ecco-jcc/jjad182.

Zhigang Liu ¹, James L Alexander ^1 2 3, Kai Yee Eng ¹, Hajir Ibraheim ^1 2, Sulak Anandabaskaran ^1 3, Aamir Saifuddin ^1 3, Laura Constable ¹, Rocio Castro Seoane ¹, Claire Bewshea ⁴, Rachel Nice ^4 5, Andrea D'Mello ⁶, Gareth R Jones ^7 8, Sharmili Balarajah ^1 2, Francesca Fiorentino ^9 10, Shaji Sebastian ^11 12, Peter M Irving ^13 14, Lucy C Hicks ^1 2, Horace R T Williams ^1 2, Alexandra J Kent ¹⁵, Rachel Linger ¹⁶, Miles Parkes ^16 17, Klaartje Kok ¹⁸, Kamal V Patel ¹⁹, Julian P Teare ^1 2, Daniel M Altmann ²⁰, Rosemary J Boyton ^21 22, Ailsa L Hart ³, Charlie W Lees ^7 8, James R Goodhand ^4 23, Nicholas A Kennedy ^4 23, Katrina M Pollock ^21 24, Tariq Ahmad ^4 23, Nick Powell ^1 2

Author information

¹Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

²Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.

³Department of Gastroenterology, St Marks Hospital and Academic Institute, Gastroenterology, London, UK.

⁴Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.

⁵Department of Clinical Chemistry, Exeter Clinical Laboratory International, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

⁶Division of Medicine & Integrated Care, Imperial College Healthcare NHS Trust, London, UK.

⁷Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK.

⁸Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.

⁹Department of Surgery and Cancer, Imperial College London, London, UK.

¹⁰Nightingale-Saunders Clinical Trials & Epidemiology Unit [King's Clinical Trials Unit], King's College London, London, UK.

¹¹Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.

¹²Hull York Medical School, University of Hull, Hull, UK.

¹³Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

¹⁴School of Immunology & Microbial Sciences, King's College London, London, UK.

¹⁵Department of Gastroenterology, King's College Hospital, London, UK.

¹⁶The NIHR Bioresource, University of Cambridge, Cambridge, UK.

¹⁷Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK.

¹⁸Department of Gastroenterology, Bart's Health NHS Trust, London, UK.

¹⁹Department of Gastroenterology, St George's Hospital NHS Trust, London, UK.

²⁰Department of Immunology and Inflammation, Imperial College London, London, UK.

²¹Department of Infectious Disease, Imperial College London, London, UK.

²²Lung Division, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK.

²³Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

²⁴NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK.

Abstract

Background and aims: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD].

Methods: We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling.

Results: Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20-0.60], p = 0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p = 0.0050), and tofacitinib (0.28 [0.14-0.57], p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p = 0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p = 0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p = 0.017), and tofacitinib (0.23 [0.10-0.56], p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 [r = 0.27; p = 0.0004] and H1N1 [r = 0.33; p < 0.0001].

Conclusions: Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses.