COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.
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Authors
Alexander, James L
Kennedy, Nicholas A
Ibraheim, Hajir
Anandabaskaran, Sulak
Saifuddin, Aamir
Castro Seoane, Rocio
Liu, Zhigang
Nice, Rachel
D'Mello, Andrea
Constable, Laura
Balarajah, Sharmili
Fiorentino, Francesca
Sebastian, Shaji
Irving, Peter M
Hicks, Lucy C
Williams, Horace RT
Kent, Alexandra J
Linger, Rachel
Parkes, Miles
Kok, Klaartje
Patel, Kamal V
Teare, Julian P
Altmann, Daniel M
Boyton, Rosemary J
Goodhand, James R
Hart, Ailsa L
Lees, Charlie W
Ahmad, Tariq
Powell, Nick
VIP study investigators
Publication Date
2022-04Journal Title
Lancet Gastroenterol Hepatol
ISSN
2468-1253
Publisher
Elsevier BV
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Alexander, J. L., Kennedy, N. A., Ibraheim, H., Anandabaskaran, S., Saifuddin, A., Castro Seoane, R., Liu, Z., et al. (2022). COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.. Lancet Gastroenterol Hepatol https://doi.org/10.1016/S2468-1253(22)00005-X
Abstract
BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations. INTERPRETATION: For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised. FUNDING: Pfizer.
Sponsorship
Wellcome Trust (220725/Z/20/Z)
Medical Research Council (MR/M00533X/1)
Crohn's and Colitis UK (M14-5)
National Institute for Health Research (NIHR) (CL-2019-21-502)
Identifiers
PMC8813209, 35123676
External DOI: https://doi.org/10.1016/S2468-1253(22)00005-X
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334831
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