You are here

  • Home
  • Archive
  • Volume 70, Issue 10
  • Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Article Text

Article menu
Download PDFPDF
Inflammatory bowel disease
Original research
Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD
  1. Nicholas A Kennedy1,2,
  2. Simeng Lin1,2,
  3. James R Goodhand1,2,
  4. Neil Chanchlani1,2,
  5. Benjamin Hamilton1,2,
  6. Claire Bewshea2,
  7. Rachel Nice2,3,
  8. Desmond Chee1,2,
  9. JR Fraser Cummings4,
  10. Aileen Fraser5,
  11. Peter M Irving6,7,
  12. Nikolaos Kamperidis8,
  13. Klaartje B Kok9,10,
  14. Christopher Andrew Lamb11,12,
  15. Jonathan Macdonald13,14,
  16. Shameer Mehta15,
  17. Richard CG Pollok16,17,
  18. Tim Raine18,
  19. Philip J Smith19,
  20. Ajay Mark Verma20,
  21. Simon Jochum21,
  22. Timothy J McDonald3,
  23. Shaji Sebastian22,23,
  24. Charlie W Lees24,25,
  25. Nick Powell26,27,
  26. Tariq Ahmad1,2
  27. Contributors to the CLARITY IBD study
  1. 1 Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  2. 2 Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
  3. 3 Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
  4. 4 Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5 Gastroenterology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
  6. 6 Gastroenterology, Guy's and St Thomas' Hospitals NHS Trust, London, UK
  7. 7 School of Immunology & Microbial Sciences, King's College London, London, UK
  8. 8 Gastroenterology, St Marks Hospital and Academic Institute, London, UK, London, UK
  9. 9 Gastroenterology, Barts and The London NHS Trust, London, UK
  10. 10 Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry Blizard Institute, London, UK
  11. 11 Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  12. 12 Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  13. 13 Gastroenterology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK
  14. 14 School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
  15. 15 Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
  16. 16 Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
  17. 17 Institute for Infection & Immunity, University of London St George's, London, UK
  18. 18 Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  19. 19 Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  20. 20 Gastroenterology, Kettering General Hospital NHS Foundation Trust, Kettering, UK
  21. 21 Roche Diagnostics GmbH, Mannheim, Baden-Württemberg, Germany
  22. 22 IBD Unit - Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK
  23. 23 Hull York Medical School, University of Hull, Hull, UK
  24. 24 Gastroenterology, Western General Hospital, Edinburgh, Edinburgh, UK
  25. 25 The University of Edinburgh Centre for Genomic and Experimental Medicine, Edinburgh, UK
  26. 26 Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  27. 27 Gastroenterology, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Dr Tariq Ahmad, Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; tariq.ahmad1{at}nhs.net

Abstract

Objective Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.

Design Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.

Results Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.

Conclusion Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.

Trial registration number ISRCTN45176516.

  • infliximab
  • inflammatory bowel disease
  • TNF
  • COVID-19
  • autoimmune disease
  • inflammatory diseases
  • CLARITY
  • vedolizumab
  • vaccine
  • ChAdOx1 nCoV-19
  • BNT162b2

Data availability statement

Data are available upon reasonable request. The study protocol including the statistical analysis plan is available at www.clarityibd.org. Individual participant deidentified data that underlie the results reported in this article will be available immediately after publication for a period of 5 years. The data will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. Proposals should be directed to tariq.ahmad1@nhs.net. To gain access data requestors will need to sign a data access agreement.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/gutjnl-2021-324789

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available upon reasonable request. The study protocol including the statistical analysis plan is available at www.clarityibd.org. Individual participant deidentified data that underlie the results reported in this article will be available immediately after publication for a period of 5 years. The data will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. Proposals should be directed to tariq.ahmad1@nhs.net. To gain access data requestors will need to sign a data access agreement.

    View Full Text

    Footnotes

    • Twitter @DrNickKennedy, @SimengLin, @JamesGoodhand, @nchanchlani1, @clairebewshea, @rachelnice3, @AileenIBDBRI, @KamperidisNik, @klaartjekok, @DrChrisLamb, @j0nnymac1, @RichadPollok, @IBD_MB, @DrPhilipJSmith, @UKGastroDr, @T_J_McDonald, @ibdseb, @charlie_lees, @NickPowellLab, @tariqahmadIBD

    • NAK, SL and JRG contributed equally.

    • NP and TA contributed equally.

    • Collaborators Contributors to the CLARITY IBD study: Barts Health NHS Trust Klaartje Kok, Farjhana Bokth, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Hafiza Khatun, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Elise Pabriaga, Nicolene Plaatjies, Kevin Samuels. Barts Health NHS Trust (paediatric): Bessie Cipriano, Kevin Samuels, Nicolene Plaatjies, Hafiza Khatun, Farjana Bokth, Elise Pabriaga, Caroline Francia. Basingstoke and North Hampshire Hospital: Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White. Birmingham Women’s and Children’s NHS Foundation Trust: Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sugrah Sultan. Bolton NHS Foundation Trust: Salil Singh, Chris Dawe, Robert Hull, Natalie Silva. Borders General Hospital: Manning Jansen, Lauren Jansen. Calderdale and Huddersfield NHS Foundation Trust: Sunil Sonwalkar, Naomi Chambers, Andrew Haigh, Lear Matapure Cambridge University Hospitals NHS Foundation Trust: Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili. Chelsea and Westminster Hospital NHS Foundation Trust: Tina Thompson, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr. Chesterfield Royal Hospital: Kath Phillis, Rachel Gascoyne. Countess Of Chester Hospital NHS Foundation Trust: Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak. Dartford and Gravesham NHS Trust: Ben Warner, Carmel Stuart, Louise Lacey. Darlington Memorial Hospital: Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp. The Dudley Group NHS Foundation Trust: Shanika de Silva, Clare Allcock, Philip Harvey. East and North Hertfordshire NHS Trust: Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter. East Lancashire Hospitals NHS Trust: Joe Collum, Farzana Masters. East Suffolk and North Essex NHS Foundation Trust: Achuth Shenoy, Alison O’Kelly. Glangwili Hospital: Aashish Kumar, Samantha Coetzee, Mihaela Peiu. Great Ormond Street Hospital: Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab. Great Western Hospitals NHS Foundation Trust: Andrew Claridge, Emily Fowler, Laura McCafferty. Guy’s and St Thomas’ NHS Foundation Trust: Peter Irving, Karolina Christodoulides, Angela Clifford, Patrick Dawson, Sailish Honap, Samuel Lim, Raphael Luber, Karina Mahiouz, Susanna Meade, Parizade Raymode, Rebecca Reynolds, Anna Stanton, Sherill Tripoli, Naomi Hare. The Hillingdon Hospitals NHS Foundation Trust: Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo. Homerton University Hospital Foundation Trust: Nora Thoua, Katherine Davidson, Jagrul Miah, Alex Hall. Hull University Teaching Hospitals NHS Trust: Shaji Sebastian, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris. Imperial College Healthcare NHS Trust: Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Mohammad Aamir Saifuddin, Hemanth Prabhudev, Sharmili Balarajah. James Paget University Hospitals NHS Foundation Trust: Helen Sutherland. Kettering General Hospital: Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally. King’s College Hospital NHS Foundation Trust: Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas. King’s College Hospital NHS Foundation Trust (paediatric): Babu Vadamalayan. King’s Mill Hospital: Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove. Liverpool University Hospitals NHS Foundation Trust: Philip J Smith, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert. London North West University Healthcare NHS Trust: Nik Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Michela Cicchetti, Mohammad Saifuddin, Priya Yesupatham. Maidstone and Tunbridge Wells NHS Trust: Rohit Gowda, Maureen Williams. Manchester University NHS Foundation Trust: Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Diamond Sathe, Jennifer Soren. The Mid Yorkshire Hospitals NHS Trust: Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton Milton Keynes University Hospital: George MacFaul, Diane Scaletta, Loria Siamia. Newcastle Hospitals NHS Foundation Trust: Chris Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight. Ninewells Hospital & Medical School: Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed. Norfolk and Norwich University Hospitals NHS Foundation Trust: Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright. North Bristol NHS Trust: Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes. North Tyneside General Hospital: Praveen Rajasekhar, Lisa Gallagher, Linda Patterson, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson. Nottingham University Hospitals NHS Trust: David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr. The Pennine Acute Hospitals NHS Trust: Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie. Portsmouth Hospitals NHS Trust: Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash. The Queen Elizabeth Hospital Kings Lynn NHS Trust: Alan Wiles, Hannah Bloxham, Jose Dias, Ellie Graham. Queen Elizabeth University Hospital, Glasgow: Jonathan Macdonald, Shona Finan, Faye McMeeken, Stephanie Shields, John Paul Seenan. Royal Berkshire NHS Foundation Trust: Des DeSilva, Ofori Boateng, Holly Lawrence, Susanna Malkakorpi. The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust: Simon Whiteoak, Kelli Edger-Earley. Royal Cornwall Hospitals NHS Trust: Sarah Ingram, Sharon Botfield, Fiona Hammonds, Clare James. Royal Devon and Exeter NHS Foundation Trust: Tariq Ahmad, Gemma Aspinall, Sarah Hawkins, Suzie Marriott, Clare Redstone, Halina Windak. Royal Free London NHS Foundation Trust: Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou. Royal Glamorgan Hospital: James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel. Royal Gwent Hospital: Evelyn Baker, Sean Cutler, Rina Mardania Evans, Maxine Nash. Royal Hampshire County Hospital: John Gordon, Emma Levell, Silvia Zagalo. Royal Hospital for Sick Children, Edinburgh: Richard Russell, Paul Henderson, Margaret Millar. Royal Manchester Children’s Hospital: Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson. Royal Surrey County Hospital: Christopher Alexakis, Natalia Michalak. Royal United Hospitals Bath: John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry. The Royal Wolverhampton NHS Trust: Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe. Salford Royal NHS Foundation Trust: Clare Ormerod, Helen Christensen, Anne Keen, Jonathan Ogor. Salisbury District Hospital: Alpha Anthony, Emily Newitt. Sandwell and West Birmingham NHS Trust: Edward Fogden, Kalisha Russell. Sheffield Teaching Hospitals NHS Foundation Trust: Anne Phillips, Muaad Abdulla. Shrewsbury and Telford Hospital NHS Trust: Jeff Butterworth, Colene Adams, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley. Singleton Hospital: Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees. Somerset NHS Foundation Trust: Emma Wesley, Alison Moss. South Tees Hospitals NHS Foundation Trust: Arvind Ramadas, Julie Tregonning. Southend University Hospital NHS Foundation Trust: Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick. St George’s University Hospitals NHS Foundation Trust: Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Richard Pollok, Mark Mencias, Abigail Seaward. St George’s University Hospitals NHS Foundation Trust (paediatric): Nicholas Reps, Rebecca Martin. St James’s University Hospital: Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey. Stockport NHS Foundation Trust: Zahid Mahmood, Racheal Campbell, Liane Marsh. Surrey and Sussex Healthcare NHS Trust: Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug. Tameside and Glossop Integrated Care NHS Foundation Trust: Vinod Patel, Joanne Vere. Torbay and South Devon NHS Foundation Trust: Gareth Walker, Stacey Atkins, Jasmine Growdon, Charlotte McNeill. University Hospitals Birmingham NHS Foundation Trust: Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff. University Hospitals Bristol NHS Foundation Trust: Aileen Fraser, Katherine Belfield. University Hospitals of Derby and Burton NHS Foundation Trust: Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding. University Hospitals of Leicester NHS Trust: John deCaestecker, Olivia Watchorn. University Hospitals Plymouth NHS Trust: Chris Hayward, Susan Inniss, Lucy Pritchard. University Hospital Southampton NHS Foundation Trust: Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Audrey Torokwa. United Lincolnshire Hospitals NHS Trust: Jervoise Andreyev, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle. University College London Hospitals NHS Foundation Trust: Shameer Mehta, James Bell, William Blad, Lisa Whitley. University Hospital Llandough: Durai Dhamaraj, Mark Baker. University Hospital of Wales (paediatric): Amar Wahid, Zoe Morrison. West Hertfordshire Hospitals NHS Trust: Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi. West Middlesex University Hospital: Emma Johnston. Western General Hospital: Metod Oblak, Richard Appleby. West Suffolk NHS Foundation Trust: Marium Asghar, Charlie Lees, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson. Withybush General Hospital: Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor. Yeovil District Hospital NHS Foundation Trust: Katie Smith, Linda Howard, Dianne Wood. York Teaching Hospital NHS Foundation Trust: Ajay Muddu, Laura Barman, Janine Mallinson. Ysbyty Gwynedd: Iona Thomas, Kelly Andrews, Caroline Mulvaney Jones, Julia Roberts.

    • Contributors NAK, JRG, CB, SS, NP and TA participated in the conception and design of this study. CB was the project manager and coordinated patient recruitment. RN and TM coordinated all biochemical analyses and central laboratory aspects of the project. SJ conducted the experiments at Roche Diagnostics to define the seroconversion threshold used in this manuscript. NAK, SL, JRG, NC, BH, DC, JRFC, AF, PMI, NK, KBK, CAL, JM, SM, RCP, TR, PJS, AMV, TJM, SS, CWL, NP and TA were involved in the acquisition, analysis or interpretation of data. Data analysis was done by NAK. Drafting of the manuscript was done by NAK, SL, JRG, NC, RN, DC, RCP, SS, CWL, NP, TA. SS, NP and TA obtained the funding for the study. All the authors contributed to the critical review and final approval of the manuscript. NAK and TA have verified the underlying data.

    • Funding This study was funded by F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), Takeda (UK), Galapagos NV (Belgium), Hull University Teaching Hospital NHS Trust, and Royal Devon and Exeter NHS Foundation Trust.

    • Competing interests NAK 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; 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. SL reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. JRG reports grants from F. Hoffmann-La Roche AG, grants from Biogen, 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. JRFC reports grants and personal fees from Samsung, Pfizer & Biogen; personal fees and non-financial support from Janssen & Abbvie; grants, personal fees and non-financial support from Takeda; personal fees from MSD, Sandoz, Celltrion & NAPP, outside the submitted work. AF reports personal fees from Takeda UK Ltd, personal fees from Dr Falk Pharma, personal fees from Tillotts, personal fees from Abbvie Ltd, personal fees from Sheild, personal fees from Ferring, from Pharmacosmos, personal fees from Allergan, personal fees from Janssen, 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. NK reports personal fees from Janssen, 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. 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. 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. PJS reports speaker fees and advisory board sponsorship from Janssen, Celltrion and Takeda outside the submitted work. AMV reports personal fees and non-financial support from Takeda, personal fees and non-financial support from Celltrion, personal fees and non-financial support from Merck Sharp & Dohme, outside the submitted work. SJ is an employee of Roche Diagnostics and holds Roche shares. SS reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Pharmacocosmos, 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. 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, 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.

    • Patient and public involvement statement We conducted an electronic survey to gauge the opinion of patients with IBD on the patient questionnaires to be delivered as part of the CLARITY IBD study. We surveyed 250 patients across 74 hospitals. All our proposed questions for study inclusion were rated as important or very important by at least 83% of participants. The Exeter IBD Patient Panel refined the questions included in the study questionnaire, reviewed the study protocol, supported the writing of the patient information sheets, and participated in testing of the electronic consent form and patient questionnaire. A member of the Exeter IBD Patient Panel sits on the study management committee, ensuring patient involvement in all aspects of study delivery, data analysis and dissemination of findings.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.