COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study

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.

Author list

 

James L Alexander, PhD *

Nicholas A Kennedy, PhD *

Hajir Ibraheim, MBBS 

Sulak Anandabaskaran, MBChB 

Aamir Saifuddin, BMBCh 

Rocio Castro Seoane, PhD 

Zhigang Liu, PhD 

Rachel Nice, MSc 

Claire Bewshea, MSc 

Andrea D'Mello, BSc 

Laura Constable, MSc 

Gareth R Jones, PhD 

Sharmili Balarajah, MBChB 

Francesca Fiorentino, PhD 

Prof Shaji Sebastian, MD 

Peter M Irving, MD 

Lucy C Hicks, PhD 

Horace R T Williams, PhD 

Alexandra J Kent, MBChB 

Rachel Linger, BSc 

Miles Parkes, DM 

Klaartje Kok, PhD 

Kamal V Patel, MBBS 

Prof Julian P Teare, MD 

Prof Daniel M Altmann, PhD 

Prof Rosemary J Boyton, PhD 

James R Goodhand, MBBS 

Prof Ailsa L Hart, PhD 

Prof Charlie W Lees, PhD 

Tariq Ahmad, PhD *

Nick Powell, PhD  *

on behalf of the

VIP study investigators †

Novel Coronavirus SARS-CoV-2

10.1016/S2468-1253(22)00005-X

The Lancet - Gastroenterology & Hepatology