Antibody Responses to Influenza Vaccination are Diminished in Patients With Inflammatory Bowel Disease on Infliximab or Tofacitinib

Zhigang Liu; James L Alexander; Kai Yee Eng; Hajir Ibraheim; Sulak Anandabaskaran; Aamir Saifuddin; Laura Constable; Rocio Castro Seoane; Claire Bewshea; Rachel Nice; Andrea D'Mello; Gareth R Jones; Sharmili Balarajah; Francesca Fiorentino; Shaji Sebastian; Peter M Irving; Lucy C Hicks; Horace R T Williams; Alexandra J Kent; Rachel Linger; Miles Parkes; Klaartje Kok; Kamal V Patel; Julian P Teare; Daniel M Altmann; Rosemary J Boyton; Ailsa L Hart; Charlie W Lees; James R Goodhand; Nicholas A Kennedy; Katrina M Pollock; Tariq Ahmad; Nick Powell

doi:10.1093/ecco-jcc/jjad182

Antibody Responses to Influenza Vaccination are Diminished in Patients With Inflammatory Bowel Disease on Infliximab or Tofacitinib

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

Authors

Zhigang Liu¹, James L Alexander^{1

2

3}, Kai Yee Eng¹, Hajir Ibraheim^{1

2}, Sulak Anandabaskaran^{1

3}, Aamir Saifuddin^{1

3}, Laura Constable¹, Rocio Castro Seoane¹, Claire Bewshea⁴, Rachel Nice^{4

5}, Andrea D'Mello⁶, 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 Kent¹⁵, Rachel Linger¹⁶, Miles Parkes^{16

17}, Klaartje Kok¹⁸, Kamal V Patel¹⁹, Julian P Teare^{1

2}, Daniel M Altmann²⁰, Rosemary J Boyton^{21

22}, Ailsa L Hart³, 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}

Affiliations

¹ Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
² Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
³ Department of Gastroenterology, St Marks Hospital and Academic Institute, Gastroenterology, London, UK.
⁴ Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
⁵ Department of Clinical Chemistry, Exeter Clinical Laboratory International, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
⁶ Division of Medicine & Integrated Care, Imperial College Healthcare NHS Trust, London, UK.
⁷ Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK.
⁸ Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
⁹ Department of Surgery and Cancer, Imperial College London, London, UK.
¹⁰ Nightingale-Saunders Clinical Trials & Epidemiology Unit [King's Clinical Trials Unit], King's College London, London, UK.
¹¹ Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
¹² Hull York Medical School, University of Hull, Hull, UK.
¹³ Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
¹⁴ School of Immunology & Microbial Sciences, King's College London, London, UK.
¹⁵ Department of Gastroenterology, King's College Hospital, London, UK.
¹⁶ The NIHR Bioresource, University of Cambridge, Cambridge, UK.
¹⁷ Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
¹⁸ Department of Gastroenterology, Bart's Health NHS Trust, London, UK.
¹⁹ Department of Gastroenterology, St George's Hospital NHS Trust, London, UK.
²⁰ Department of Immunology and Inflammation, Imperial College London, London, UK.
²¹ Department of Infectious Disease, Imperial College London, London, UK.
²² Lung Division, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK.
²³ Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
²⁴ NIHR 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.

Keywords: JAK-inhibitor; anti-TNF; humoral immunity; immunisation.

MeSH terms

Adult
Antibodies, Viral / blood
Antibody Formation / drug effects
Antibody Formation / immunology
Case-Control Studies
Female
Humans
Immunosuppressive Agents / therapeutic use
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / immunology
Infliximab* / therapeutic use
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H3N2 Subtype / immunology
Influenza Vaccines* / immunology
Influenza, Human / immunology
Influenza, Human / prevention & control
Male
Middle Aged
Piperidines* / therapeutic use
Prospective Studies
Pyrimidines* / therapeutic use

Substances

tofacitinib
Piperidines
Influenza Vaccines
Pyrimidines
Infliximab
Immunosuppressive Agents
Antibodies, Viral

Abstract

MeSH terms

Substances

Grants and funding