Abstract
Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-Treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.
Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.
Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-Treated than vedolizumab-Treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-Treated than vedolizumab-Treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001).
Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-Treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.
Trial registration number: ISRCTN45176516.
| Original language | English |
|---|---|
| Pages (from-to) | 865-875 |
| Number of pages | 11 |
| Journal | Gut |
| Volume | 70 |
| Issue number | 5 |
| Early online date | 22 Mar 2021 |
| DOIs | |
| Publication status | Published - 1 May 2021 |
Keywords
- autoimmune disease
- clarity
- COVID-19
- inflammatory bowel disease
- inflammatory diseases
- infliximab
- vedoluzimab
ASJC Scopus subject areas
- Gastroenterology
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In: Gut, Vol. 70, No. 5, 01.05.2021, p. 865-875.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab
AU - Kennedy, Nicholas A.
AU - Goodhand, James R.
AU - Bewshea, Claire
AU - Nice, Rachel
AU - Chee, Desmond
AU - Lin, Simeng
AU - Chanchlani, Neil
AU - Butterworth, Jeffrey
AU - Cooney, Rachel
AU - Croft, Nicholas M.
AU - Hart, Ailsa L.
AU - Irving, Peter M.
AU - Kok, Klaartje B.
AU - Lamb, Christopher A.
AU - Limdi, Jimmy K.
AU - MacDonald, Jonathan
AU - McGovern, Dermot P. B.
AU - Mehta, Shameer J.
AU - Murray, Charles D.
AU - Patel, Kamal V.
AU - Pollok, Richard C. G.
AU - Raine, Timothy
AU - Russell, Richard K.
AU - Selinger, Christian P.
AU - Smith, Philip J.
AU - Bowden, Jack
AU - McDonald, Timothy J.
AU - Lees, Charlie W.
AU - Sebastian, Shaji
AU - Powell, Nicholas
AU - Ahmad, Tariq
A2 - Mowat, Craig
N1 - Funding Information: Competing interests NAK reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, nonfinancial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Takeda, personal fees and non-financial support from Dr Falk, outside the submitted work. JRG reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. DC reports non-financial support from Ferring, personal fees and non-financial support from Pfizer, outside the submitted work. SL reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. RC reports personal fees from Takeda, outside the submitted work. NMC reports trial funding, advisory board and speaker fees paid to his institution from AbbVie, Eli Lilly, Takeda, Shire, Pfizer and Janssen. ALH reports personal fees from Abbvie, personal fees from Allergan, personal fees from BMS, personal fees from Celltrion, personal fees from Falk, personal fees from GSK, personal fees from Takeda, personal fees from Pfizer, personal fees from Janssen, personal fees from Galapogos, personal fees from Astra Zeneca, outside the submitted work. PMI reports grants and personal fees from Takeda, grants from MSD, grants and personal fees from Pfizer, personal fees from Galapagos, personal fees from Gilead, personal fees from Abbvie, personal fees from Janssen, personal fees from Boehringer Ingelheim, personal fees from Topivert, personal fees from VH2, personal fees from Celgene, personal fees from Arena, personal fees from Samsung Bioepis, personal fees from Sandoz, personal fees from Procise, personal fees from Prometheus, outside the submitted work. KBK reports personal fees from Janssen, personal fees from Takeda, personal fees from PredictImmune, personal fees from Amgen, outside the submitted work. CAL reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr Falk Pharma, grants from AstraZeneca, outside the submitted work. JKL reports personal fees from MSD, personal fees from Janssen, grants and personal fees from Takeda, grants and personal fees from Galapagos, personal fees from Tillotts, outside the submitted work. JM reports grants and personal fees from Takeda Pharmaceuticals, grants and personal fees from Biogen, personal fees and non-financial support from AbbVie, personal fees from Grifols, personal fees from Sandoz, personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Vifor Pharmaceuticals, personal fees from Predictimmune, personal fees from Bristol Myers Squibb, non-financial support from Ferring Pharmaceuticals, outside the submitted work. DPBM reports grants from the Leona M. and Harry B. Helmsley Charitable Trust, during the conduct of the study; personal fees from Takeda Pharmaceuticals, personal fees from Pfizer, personal fees from Bridge Biotherapeutics, personal fees from Palatin Technologies, personal fees from Boehringer-Ingelheim, personal fees and other from Prometheus Biosciences, personal fees from Gilead, outside the submitted work. KVP reports personal fees and non-financial support from Takeda, personal fees and non-financial support from Janssen, personal fees and non-financial support from Abbvie, personal fees from DrFalk, non-financial support from Ferring, outside the submitted work. RCGP reports acting as consultant, advisory board member, speaker or recipient of educational grant from Dr Falk, Ferring, Janssen, Pharmacosmos and Takeda. TR reports grants and personal fees from Abbvie, personal fees from BMS, personal fees from Celgene, personal fees from Ferring, personal fees from Gilead, personal fees from GSK, personal fees from LabGenius, personal fees from Janssen, personal fees from Mylan, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sandoz, personal fees from Takeda, personal fees from Galapagos, personal fees from Arena, outside the submitted work. RKR reports grants from NHS Research Scotland Senior Research Fellowship, personal fees from Nestlé, personal fees from AbbVie, personal fees from Dr Falk, personal fees from Takeda, personal fees from Napp, personal fees from Mead Johnson, personal fees from Nutricia, personal fees from 4D Pharma, outside the submitted work. CPS reports grants and personal fees from AbbVie, grants and personal fees from Janssen, grants and personal fees from Takeda, personal fees from Dr Falk, personal fees from Pfizer, personal fees from Galapagos, personal fees from Arena, personal fees from Fresenius Kabi, outside the submitted work. PJS reports speaker fees and advisory board sponsorship from Janssen, Celltrion and Takeda outside the submitted work. CWL reports personal fees from Abbvie, personal fees from Janssen, personal fees from Pfizer, personal fees from Takeda, grants from Gilead, personal fees from Gilead, personal fees from Galapagos, personal fees from Iterative Scopes, personal fees from Trellus Health, personal fees from Celltion, personal fees from Ferring, personal fees from BMS, during the conduct of the study. SS reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Phamrmacocosmos, outside the submitted work. NP reports personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Abbvie, personal fees from Roche, personal fees from Lilly, personal fees from Allergan, personal fees from Celgene, outside the submitted work; and NP has served as a speaker/advisory board member for Abbvie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. TA reports grants and non-financial support from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen Inc, grants and personal fees from Celltrion Healthcare, personal fees and non-financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non-financial support from Tillotts, outside the submitted work. Funding Information: CLARITY IBD is an investigator-led, UK National Institute for Health Research COVID-19 urgent public health study funded by the Royal Devon and Exeter NHS Foundation Trust, Hull University Teaching Hospital NHS Trust and by unrestricted educational grants from F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH(Switzerland), Celltrion Healthcare (South Korea) and Galapagos NV (Belgium). Funding Information: Funding This study was funded by F. Hoffmann-La Roche, Hull University Teaching Hospital NHS Trust, Biogen GmbH (Switzerland), Celltrion Healthcare, Galapagos NV, Royal Devon and Exeter NHS Foundation Trust. Funding Information: 11Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK 12Department of Gastroenterology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK 13Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK 14Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester, UK 15Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK 16Department of Gastroenterology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK 17F. Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA 18Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK 19Department of Gastroenterology, Royal Free London NHS Foundation Trust, London, UK 20Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, London, UK 21Institute for Infection and Immunity, University of London, London, UK 22Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 23Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK 24Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK 25Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK 26Medical School, University of Exeter, Exeter, UK 27Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK 28Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK 29Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK 30Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK 31Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK Twitter Nicholas A Kennedy @DrNickKennedy, James R Goodhand @ JamesGoodhand, Claire Bewshea @clairebewshea, Rachel Nice @rachelnice3, Simeng Lin @SimengLin, Neil Chanchlani @nchanchlani1, Jeffrey Butterworth @ jrbutterworth1, Rachel Cooney @rachelcooney7, Nicholas M Croft @nickcrofty, Ailsa L Hart @DrAilsaHart, Klaartje B Kok @klaartjekok, Christopher A Lamb @ DrChrisLamb, Jimmy K Limdi @jklimdi, Jonathan Macdonald @j0nnymac1, Dermot PB McGovern @doc_ibd, Charles D Murray @CharlieMuz, Richard CG Pollok @ RichardPollok, Philip J Smith @DrPhilipJSmith, Jack Bowden @jack_bowdenjack, Timothy J McDonald @T_J_McDonald, Charlie W Lees @charlie_lees, Shaji Sebastian @NhsSeb, Nicholas Powell @NickPowellLab, Tariq Ahmad @tariqahmadIBD and Contributors to the CLARITY IBD study @clarityibd Acknowledgements CLARITY IBD is a UK National Institute for Health Research (NIHR) Urgent Public Health Study. The NIHR Clinical Research Network supported study set-up, site identification and delivery of this study. This was facilitated by Professor Mark Hull, the national specialty lead for gastroenterology. We acknowledge the contribution of our Patient Advisory Group who helped shape the trial design around patient priorities. Our partner, Crohn’s and Colitis UK (CCUK), continues to support this group and participate in study management team meetings. Laboratory tests were undertaken by the Exeter Blood Sciences Laboratory at the Royal Devon and Exeter NHS Foundation Trust. The Exeter NIHR Clinical Research Facility coordinated sample storage and management. Tariq Malik and James Thomas from Public Health England; Guy Stevens, Katie Donelon and Elen de Lacy from Public Health Wales; and Johanna Bruce from Public Health Scotland supported linkage of central SARS-CoV-2 PCR test results with study data. Roche Diagnostics Limited provided the Elecsys Anti-SARS-CoV-2 immunoassay for the study. SL is supported by a Wellcome GW4-CAT fellowship. NC acknowledges support from CCUK. CAL acknowledges support from the NIHR Newcastle Biomedical Research Centre and the support of the Programmed Investigation Unit at Royal Victoria Infirmary, Newcastle on Tyne. TR acknowledges support with recruitment from the NIHR Cambridge Biomedical Research Centre (BRC). RKR is supported by an NHS Research Scotland Senior Research Fellowship. NP is supported by the NIHR Imperial BRC. We acknowledge the study coordinators of the Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group: Marian Parkinson and Helen Gardner-Thorpe for their ongoing administrative support to the study. The sponsor of the study was the Royal Devon and Exeter NHS Foundation Trust. Publisher Copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-Treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-Treated than vedolizumab-Treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-Treated than vedolizumab-Treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001).Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-Treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration number: ISRCTN45176516.
AB - Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-Treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-Treated than vedolizumab-Treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-Treated than vedolizumab-Treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001).Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-Treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration number: ISRCTN45176516.
KW - autoimmune disease
KW - clarity
KW - COVID-19
KW - inflammatory bowel disease
KW - inflammatory diseases
KW - infliximab
KW - vedoluzimab
UR - http://www.scopus.com/inward/record.url?scp=85103395730&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2021-324388
DO - 10.1136/gutjnl-2021-324388
M3 - Article
C2 - 33753421
AN - SCOPUS:85103395730
SN - 0017-5749
VL - 70
SP - 865
EP - 875
JO - Gut
JF - Gut
IS - 5
ER -