New evidence indicates the commonly-prescribed inflammatory bowel disease (IBD) drug infliximab blunts the immune system to COVID-19 infection, potentially increasing the risk of reinfection.
The findings arose from the CLARITY study, which recruited 6,935 patients with Crohn's disease and ulcerative colitis from 92 UK hospitals between September and December 2020. It found that fewer than half of people with IBD who were treated with infliximab had detectable antibodies after SARS-CoV-2 infection, the coronavirus that causes COVID-19.
The study is led by gastroenterologists at the Royal Devon and Exeter NHS Foundation Trust and the University of Exeter Medical School and supported by Crohn's and Colitis UK and the UK National Institute for Health Research (NIHR).
The authors say an impaired immune response may boost susceptibility to recurrent COVID-19 and help drive the evolution of new variants of SARS-CoV-2, the virus responsible for the infection, warn the researchers. However, they are encouraging people to continue to take their medication as overall Covid-19 risk remains very low.
Careful monitoring of patients with IBD treated with infliximab, who have been vaccinated against COVD-19, will be needed to ensure they mount a strong enough antibody response to ward off the infection, they advise. CLARITY study lead, Professor Tariq Ahmad, of the University of Exeter Medical School, said: "The poor antibody responses observed in patients treated with infliximab raise the possibility that some patients may not develop protective immunity after COVID-19 infection, and might be at increased risk of reinfection. What we don't yet know is how use of anti-TNF drugs will impact antibody responses to vaccination."
The study underlines the importance of fast-paced research to address important questions in people affected by IBD. Professor Ahmad said: "The CLARITY IBD study will continue to follow participants for 40 weeks to investigate important questions regarding the impact of immunosuppressive drugs on immunity to SARS-CoV-2 infection and COVID-19. Modified vaccine schedules may be required if impaired antibody responses are also observed following vaccination. However, because the overall risk of COVID-19 is low in this patient group, we would still strongly encourage patients to continue to take anti-TNF medicines."
Around two million people worldwide are prescribed anti-tumour necrosis factor (anti-TNF)drugs, which include infliximab. Anti-TNF drugs are effective treatments for immune-mediated inflammatory diseases, but by suppressing the immune system, they can reduce vaccine effectiveness and increase risk of serious infection. The CLARITY study, published in GUT, sought to investigate the impact of infliximab on immune responses to SARS-CoV-2 in patients with IBD.
500,000 people across the UK live with Inflammatory bowel disease (IBD) of which ulcerative colitis and Crohn's disease, are the two main forms. Symptoms include urgent and frequent bloody diarrhoea, weight loss, pain, and extreme fatigue. At the start of the COVID-19 pandemic the UK Government advised that patients taking anti-TNF medicines could be at increased risk of complications from coronavirus. All were advised to follow strict social distancing measures, and some, depending on the severity of their condition, were advised to shield.
In the CLARITY study researchers compared antibody responses to SARS-CoV-2 in patients treated with infliximab to an alternative medication, vedolizumab that blocks inflammatory cells entering the gut without reducing immune responses to infections or vaccinations. Rates of COVID-19 infection and hospitalisations were similar between infliximab- and vedolizumab-treated patients. However, infliximab-treated patients were much less likely to subsequently have a positive antibody test. These findings could not, therefore, be explained by differences in acquisition or severity of infection alone. Rather, infliximab seemed to be directly influencing antibody responses to infection. In keeping with this idea, rates of positive antibody tests were lowest in participants who were also taking other drugs that suppress the immune system, such as azathioprine, mercaptopurine or methotrexate.
Dr Nick Powell, of Imperial College London, said the CLARITY team is now exploring the role of other elements of the immune system, which may still protect against reinfection. "Although we clearly observed diminished antibody responses in patients taking infliximab, we haven't yet completed our investigation of T-cell and other protective immune responses against the virus. I would expect that even in the presence of less efficient antibody production, infliximab-treated patients will mobilise some protective aspect of their immune system to defend themselves."
Professor Danny Altmann, Professor of Immunology, at Imperial College London, said: "Many people with IBD who are taking infliximab have been shielding throughout this pandemic, so little is known about their susceptibility to COVID-19. They're not eligible for phase 3 trials so there's also a knowledge gap around their vaccine response. At this stage it's really key to start to collect the 'real life' data about their immunity and susceptibility. This study starts to offer some answers, including how best to understand and monitor how these individuals progress coming out of shielding and how well they respond to vaccination."
Sarah Sleet, Chief Executive Officer at Crohn's & Colitis UK, said: "The CLARITY results are an important first step in helping us understand how different medicines for Crohn's and Colitis affect a person's response to coronavirus. At this stage the key message is people with Crohn's and Colitis should keep taking their medication to stay well and take the vaccine when offered. But we also need research like this to continue. A huge number of people with Crohn's and Colitis have had to contend with the stresses of shielding and social distancing, and it's vital this group is prioritised in research."
The paper is entitled "Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab", published in GUT.
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