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

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 vaccineinduced 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 recipie...

Serological Responses to the First Three Doses of SARS-CoV-2 Vaccination in Inflammatory Bowel Disease: A Prospective Cohort Study

“…25 A prior study showed that antibody titres fell by 21% per decade of life following the 2 nd dose of vaccine. 6 Similarly, our models also indicated decreases in antibody concentration per decade of life across 1 st and 2 nd doses. For example, immediately after 2 nd dose of the vaccine, antibody titres were 12% lower per decade of advancing age (Video 1).…”

“…26 Our data are consistent with previous studies in demonstrating diminished antibody responses following two doses of a SARS-CoV-2 vaccine for patients on anti-TNF therapy, combination immunosuppressive therapies, and corticosteroids. [6][7][8][9][10][11]24,27,28 In contrast, our study showed that the 3 rd dose of the vaccine yielded high antibody titres across all classes of medications used for maintenance of remission in IBD. However, administration of vaccine while concurrently taking prednisone yielded lower antibody response following 1 st , 2 nd , and 3 rd dose of the vaccine.…”

“…Older age was associated with decreased antibody titres after 1 st and 2 nd doses in prior studies, [6][7][8] which is clinically relevant as seniors with IBD are at highest susceptibility to severe COVID-19. 25 A prior study showed that antibody titres fell by 21% per decade of life following the 2 nd dose of vaccine.…”

Favourable vaccine-induced SARS-CoV-2 specific T cell response profile in patients undergoing immune-modifying therapies

“…Others have already shown that these therapies, particularly TNF inhibitors, reduce the ability of different COVID-19 vaccines (based on mRNA or Adenoviral vector) to produce Spike-specific antibodies (5–8) and recognize SARS-CoV-2 variants including B.1.617.2 (Delta) (4). Such results are expected, since reduced humoral responses to other vaccines (i.e.…”

Uptake of third doses of SARS-CoV-2 vaccines among people with inflammatory bowel disease in Ontario, Canada

“…Patients with inflammatory bowel disease (IBD) are often treated with immunosuppressive medications, which are associated with decreased antibody response to initial SARS-CoV-2 vaccination and waning antibody levels following a second dose. 1 , 2 The province of Ontario, Canada began offering third doses of SARS-CoV-2 vaccines to priority groups, including individuals with IBD on immunosuppressive therapy, beginning Sept 14, 2021, 3 followed by everyone aged 18 years and older on Dec 20, 2021. 4 We describe and compare vaccine uptake in people with and without IBD as of Jan 9, 2022.…”