OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients
Lin, S.(1,2);Kennedy, N.A.(1,2);Saifuddin, A.(3,4);Muñoz Sandoval, D.(5);Reynolds, C.J.(5);Seoane, R.C.(6);Kottoor, S.H.(4);Pieper, F.P.(5);Lin, K.M.(5);Butler, D.K.(5);Chanchlani, N.(1,2);Nice, R.(2,7);Chee, D.(1,2);Bewshea, C.(2);Janjua, M.(1,2);McDonald, T.J.(7);Sebastian, S.(8,9);Alexander, J.L.(4,10);Constable, L.(4);Lee, J.C.(11,12,13);Murray, C.D.(11);Hart, A.L.(3);Irving, P.M.(14,15);Jones, G.R.(16,17);Kok, K.B.(18,19);Lamb, C.A.(20,21);Lees, C.W.(16,22);Altmann, D.M.(6);Boyton, R.J.(5,23);Goodhand, J.R.(1,2);Powell, N.(4,10);Ahmad, T.(1,2);
(1)Royal Devon and Exeter NHS Foundation Trust, Gastroenterology, Exeter, United Kingdom;(2)University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, United Kingdom;(3)St Marks Hospital and Academic Institute, Gastroenterology, London, United Kingdom;(4)Imperial College London, Metabolism- Digestion and Reproduction, London, United Kingdom;(5)Imperial College London, Infectious Disease, London, United Kingdom;(6)Imperial College London, Immunology and Inflammation, London, United Kingdom;(7)Royal Devon and Exeter NHS Foundation Trust, Biochemistry- Exeter Clinical Laboratory International, Exeter, United Kingdom;(8)Hull University Teaching Hospitals NHS Trust, Gastroenterology, Hull, United Kingdom;(9)University of Hull, Hull York Medical School, Hull, United Kingdom;(10)Imperial College Healthcare NHS Trust, Gastroenterology, London, United Kingdom;(11)Royal Free London NHS Foundation Trust, Gastroenterology, London, United Kingdom;(12)University of Cambridge, Cambridge Institute of Therapeutic Immunology and Infectious Disease- Jeffrey Cheah Biomedical Centre, Cambridge, United Kingdom;(13)The Francis Crick Institute, Genetic Mechanisms of Disease Laboratory, London, United Kingdom;(14)Guy's and St Thomas' NHS Foundation Trust, Gastroenterology, London, United Kingdom;(15)King's College London, School of Immunology & Microbial Sciences, London, United Kingdom;(16)Western General Hospital- NHS Lothian, Gastroenterology, London, United Kingdom;(17)The University of Edinburgh, Centre for Inflammation Research- The Queen’s Medical Research Institute, Edinburgh, United Kingdom;(18)Royal London Hospital- Barts Health NHS Trust, Gastroenterology, London, United Kingdom;(19)Barts and the London School of Medicine- Queen Mary, Centre for Immunobiology- Blizard Institute, London, United Kingdom;(20)Newcastle upon Tyne Hospitals NHS Foundation Trust, Gastroenterology, Newcastle upon Tyne, United Kingdom;(21)Newcastle University, Translational & Clinical Research Institute- Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom;(22)University of Edinburgh, Institute of Genetic and Molecular Medicine, Edinburgh, United Kingdom;(23)Royal Brompton Hospital and Harefield Hospitals, Lung Division, London, United Kingdom; CLARITY IBD
Background
Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody.
Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination.
Methods
Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine.
Results
Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1).
Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 – 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2).
There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumab-treated patients after one or two doses of either vaccine.
Antibody half-life was shorter in infliximab- than vedolizumab-treated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 – 4.1] vs 7.2 weeks [95% CI 6.8 – 7.6]) and ChAdOx1 nCoV-19 (5.3 weeks [95% CI 5.1 – 5.5] vs 9.3 weeks [95% CI 8.5 – 10.2], p value < 0.0001).
Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3).
Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 – 0.99], p = 0.035).
Conclusion
Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.