- Fecal Incontinence
|Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab
Gut. 2021 Mar 22;gutjnl-2021-324388. doi: 10.1136/gutjnl-2021-324388. Online ahead of print.
Nicholas A Kennedy # 1 2, James R Goodhand # 1 2, Claire Bewshea 2, Rachel Nice 2 3, Desmond Chee 1 2, Simeng Lin 1 2, Neil Chanchlani 1 2, Jeffrey Butterworth 4, Rachel Cooney 5, Nicholas M Croft 6 7, Ailsa L Hart 8, Peter M Irving 9 10, Klaartje B Kok 7 11, Christopher A Lamb 12 13, Jimmy K Limdi 14 15, Jonathan Macdonald 16, Dermot Pb McGovern 17, Shameer J Mehta 18, Charles D Murray 19, Kamal V Patel 20, Richard Cg Pollok 20 21, Timothy Raine 22, Richard K Russell 23, Christian P Selinger 24, Philip J Smith 25, Jack Bowden 26, Timothy J McDonald 3, Charlie W Lees 27 28, Shaji Sebastian 29, Nicholas Powell # 30 31, Tariq Ahmad # 32 2, Contributors to the CLARITY IBD study
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, Bessie Cipriano, Kevin Samuels, Nicolene Plaatjies, Hafiza Khatun, Farjana Bokth, Elise Pabriaga, Caroline Francia, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sugrah Sultan, Salil Singh, Chris Dawe, Robert Hull, Natalie Silva, Manning Jansen, Lauren Jansen, Sunil Sonwalkar, Naomi Chambers, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina Thompson, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Kath Phillis, Rachel Gascoyne, Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak, Carmel Stuart Ben Warner, Louise Lacey, Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp, Shanika de Silva, Clare Allcock, Philip Harvey, Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter, Joe Collum, Farzana Masters, Achuth Shenoy, Alison O'Kelly, Aashish Kumar, Samantha Coetzee, Mihaela Peiu, Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab, Andrew Claridge, Emily Fowler, Laura McCafferty, 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, Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo, Nora Thoua, Katherine Davidson, Jagrul Miah, Alex Hall, Shaji Sebastian, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris, Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Mohammad Aamir Saifuddin, Hemanth Prabhudev, Sharmili Balarajah, Helen Sutherland, Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally, Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas, Babu Vadamalayan, Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove, Philip J Smith, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert, Nik Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Michela Cicchetti, Mohammad Saifuddin, Priya Yesupatham, Rohit Gowda, Maureen Williams, Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Diamond Sathe, Jennifer Soren, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, George MacFaul, Diane Scaletta, Loria Siamia, Chris Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight, Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed, Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright, Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes, Praveen Rajasekhar, Lisa Gallagher, Linda Patterson, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson, David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr, Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie, Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash, Alan Wiles, Hannah Bloxham, Jose Dias, Ellie Graham, Jonathan Macdonald, Shona Finan, Faye McMeeken, Stephanie Shields, John Paul Seenan, Ofori Boateng Des DeSilva, Holly Lawrence, Susanna Malkakorpi, Simon Whiteoak, Kelli Edger-Earley, Sarah Ingram, Sharon Botfield, Fiona Hammonds, Clare James, Tariq Ahmad, Gemma Aspinall, Sarah Hawkins, Suzie Marriott, Clare Redstone, Halina Windak, Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou, James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel, Evelyn Baker, Sean Cutler, Rina Mardania Evans, Maxine Nash, John Gordon, Emma Levell, Silvia Zagalo, Richard Russell, Paul Henderson, Margaret Millar, Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson, Christopher Alexakis, Natalia Michalak, John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry, Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe, Clare Ormerod, Helen Christensen, Anne Keen, Jonathan Ogor, Alpha Anthony, Emily Newitt, Edward Fogden, Kalisha Russell, Anne Phillips, Muaad Abdulla, Jeff Butterworth, Colene Adams, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley, Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees, Emma Wesley, Alison Moss, Arvind Ramadas, Julie Tregonning, Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick, Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Richard Pollok, Mark Mencias, Abigail Seaward, Nicholas Reps, Rebecca Martin, Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey, Zahid Mahmood, Racheal Campbell, Liane Marsh, Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug, Vinod Patel, Joanne Vere, Gareth Walker, Stacey Atkins, Jasmine Growdon, Charlotte McNeill, Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff, Aileen Fraser, Katherine Belfield, Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding, John deCaestecker, Olivia Watchorn, Chris Hayward, Susan Inniss, Lucy Pritchard, Jr Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Audrey Torokwa, Jervoise Andreyev, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle, Shameer Mehta, James Bell, William Blad, Lisa Whitley, Durai Dhamaraj, Mark Baker, Amar Wahid, Zoe Morrison, Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi, Emma Johnston, Metod Oblak, Richard Appleby, Marium Asghar, Charlie Lees, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson, Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor, Katie Smith, Linda Howard, Dianne Wood, Ajay Muddu, Laura Barman, Janine Mallinson, Iona Thomas, Kelly Andrews, Caroline Mulvaney Jones, Julia Roberts
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.