OP21 COVID-19 vaccine-induced antibody responses are impaired in Inflammatory Bowel Disease patients treated with infliximab, ustekinumab or tofacitinib, but not thiopurines or vedolizumab
Alexander, J.(1,2);Kennedy, N.(3,4);Ibraheim, H.(1,2);Anandabaskaran, S.(1,5);Saifuddin, A.(1,5);Castro Seoane, R.(1);Liu, Z.(1);Nice, R.(4,6);Bewshea, C.(4);D'Mello, A.(7);Constable, L.(1);Jones, G.R.(8,9);Balarajah, S.(1,2);Fiorentino, F.(10);Sebastian, S.(11,12);Irving, P.M.(13,14);Hicks, L.(1,2);Williams, H.(1,2);Kent, A.(15);Linger, R.(16);King, R.(16);Parkes, M.(16,17);Kok, K.(18);Patel, K.(19);Altmann, D.(20);Boyton, R.(21);Goodhand, J.(3,4);Hart, A.(5);Lees, C.(8,9);Ahmad, T.(3,4);Powell, N.(1,2);
(1)Imperial College London, Metabolism- Digestion & Reproduction, London, United Kingdom;(2)Imperial College Healthcare NHS Trust, Gastroenterology, London, United Kingdom;(3)Royal Devon and Exeter NHS Foundation Trust, Gastroenterology, Exeter, United Kingdom;(4)University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, United Kingdom;(5)St Marks Hospital and Academic Institute, Gastroenterology, London, United Kingdom;(6)Royal Devon and Exeter NHS Foundation Trust, Biochemistry- Exeter Clinical Laboratory International, Exeter, United Kingdom;(7)Imperial College Healthcare NHS Trust, Medicine & Integrated Care, London, United Kingdom;(8)Western General Hospital - NHS Lothian, Gastroenterology, Edinburgh, United Kingdom;(9)The University of Edinburgh, Centre for Inflammation Research - The Queen’s Medical Research Institute, Edinburgh, United Kingdom;(10)Imperial College London, Department of Surgery and Cancer, London, United Kingdom;(11)Hull University Teaching Hospitals NHS Trust, Gastroenterology, Hull, United Kingdom;(12)University of Hull, Hull York Medical School, Hull, United Kingdom;(13)Guy's and St Thomas' NHS Foundation Trust, Gastroenterology, London, United Kingdom;(14)King's College London, School of Immunology & Microbial Sciences, London, United Kingdom;(15)King's College Hospital, Gastroenterology, London, United Kingdom;(16)University of Cambridge, NIHR Bioresource, Cambridge, United Kingdom;(17)Cambridge University Hospitals NHS Trust, Gastroenterology, Cambridge, United Kingdom;(18)Bart's Health NHS Trust, Gastroenterology, London, United Kingdom;(19)St George's Hospital NHS Trust, Gastroenterology, London, United Kingdom;(20)Imperial College London, Immunology and Inflammation, London, United Kingdom;(21)Imperial College London, Department of Infectious Disease, London, United Kingdom;
Background
Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD.
Methods
We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/mL, which correlated with 20% viral neutralization).
Results
Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69],p=0.002) and uste (0.56 [95% CI 0.31-1.00],p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11],p=0.17) or vedo (1.01 [95% CI 0.61-1.68],p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96],p<0.0001) and older age (0.82 [95% CI 0.73-0.91],p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste.
Conclusion
COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual’s immunosuppressive treatment.
Financial support was provided as a Research Grant by Pfizer Ltd.