Journal Article

Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Kane, Patricia, Layug, Reina, Sutherland, Helen, Chee, Desmond, Pakou, Glykeria, Dias, Jose, Des DeSilva, Ofori Boateng, Turnbull, Jack, Hammonds, Fiona, Sultan, Sugrah, Lockwood, Carol, Cabreros, Leilani, King, Andrew, Connor, Lynda, Claridge, Andrew, Adedoyin, Temi, Fraser, Wendy, Barman, Laura, Ward, Jill, Brown, Jeannette, Wright, Catherine, Whiteoak, Simon, Lees, Charlie W, Christodoulides, Karolina, Hong, Kate, Whitehead, Emma, Henderson, Paul, Peiu, Mihaela, Din, Said, Mencias, Mark, Moran, Gordon, Sprakes, Michael, El-Khouly, Sara, Patel, Kamal, Michalak, Natalia, Chanchlani, Neil, Harvey, Philip, Hicks, Lucy, Kapizioni, Christina, Hayes, Melony, Avanzi, Laura, Jeynes, Nouf, Baxter, Helen, Jansen, Lauren, Stroud, Natalie, Hendy, Philip, Roberts, Julia, Lofthouse, Martina, Morris, Mary Anne, Sherris, Leanne, Cutler, Sean, Jessup-Dunton, Ellen, Cipriano, Bessie, Vere, Joanne, Covil, Kate, Quartey, Doris, Kemp, Cheryl, Redstone, Clare, Abdulla, Muaad, Al-Bakir, Ibrahim, Dawe, Chris, Allcock, Clare, Diaba, Cynthia, Joefield, Teishel, Childs, Danielle, Soren, Jennifer, Moss, Alison, Kok, Klaartje B, Coke, Louise, Warn

2021

Overview

ObjectiveAntitumour 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.DesignAntibody 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.ResultsRates 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).ConclusionsInfliximab 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.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Antibodies / Antibodies, Monoclonal, Humanized - therapeutic use / Antibodies, Viral - immunology / Antibody Formation - immunology / autoimmune disease / clarity / Coronaviruses / COVID-19 / COVID-19 - epidemiology / Disease transmission / Drugs / Evolution / Female / Gastrointestinal Agents - therapeutic use / Hepatitis / Hospitals / Humans / Immunoassay / Immunomodulation / Infections / Inflammatory Bowel Disease / Inflammatory Bowel Diseases - drug therapy / Inflammatory diseases / Infliximab / Infliximab - therapeutic use / Influenza / Laboratories / Male / Middle Aged / Monoclonal antibodies / Pandemics / Patients / Prospective Studies / Public health / SARS-CoV-2 - immunology / Seroconversion / Serologic Tests / Serology / Severe acute respiratory syndrome coronavirus 2 / Social distancing / TNF inhibitors / Tumor necrosis factor-TNF / Tumor necrosis factor-α / United Kingdom - epidemiology / Vaccination / Vaccines / vedoluzimab