COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study
Authors: James L Alexander, Nicholas A Kennedy, Hajir Ibraheim, Sulak Anandabaskaran, Aamir Saifuddin, Rocio Castro Seoane, Zhigang Liu, 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 Williams, Alexandra J Kent, Rachel Linger, Miles Parkes, Klaartje Kok, Kamal V Patel, Julian P Teare, Daniel M Altmann, Rosemary J Boyton, James R Goodhand, Ailsa L Hart, Charlie W Lees, 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
Journal: The Lancet. Gastroenterology & hepatology (2022)

BackgroundThe 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.MethodsIn 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.FindingsBetween 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.InterpretationFor 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.FundingPfizer.