Common inflammatory bowel disease treatment is linked to reduced COVID-19 antibody response

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, including GOSH, 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 authors say an impaired immune response may make someone more susceptible to recurrent COVID-19 and encourage new variants of SARS-CoV-2. However, they are encouraging people to continue to take their medication as the 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.

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.

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.”

The CLARITY study continues until the end of 2021.

The full paper “Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab” was published in GUT.