Crohn's drug blunts immune response against coronavirus, study suggests

A drug used to treat inflammatory bowel disease (IBD) like Crohn's or ulcerative colitis may blunt the immune system's response against the coronavirus, research suggests.

So-called anti-tumour necrosis factor (anti-TNF) treatments suppress the production of an inflammatory protein involved in IBD.

Although effective, the drugs are known to dampen the immune response following certain vaccinations, as well as increasing the risk of serious respiratory infections.

To better understand the medications' impact amid the pandemic, medics from the Royal Devon and Exeter NHS Foundation Trust analysed close to 7,000 IBD patients, around two-thirds of which were treated with the anti-TNF drug infliximab.

The remainder were on the medication vedolizumab, which is not associated with increased infection susceptibility.

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Results reveal that the infliximab-treated patients who caught the coronavirus went on to have fewer infection-fighting antibodies in the blood.

This could leave IBD patients vulnerable to recurrent coronavirus infections, as well as potentially prompting the evolution of new variants, warn the medics.

"The poor antibody responses observed in patients treated with infliximab raise the possibility some patients may not develop protective immunity after COVID-19 [the disease caused by the coronavirus] infection and might be at increased risk of reinfection," said lead author Professor Tariq Ahmad, from the University of Exeter.

"What we don't yet know is how use of anti-TNF drugs will impact antibody responses to vaccination."

Although unclear, IBD may be partially caused by a patient's immune system mistakenly attacking their digestive tract. Drugs that suppress the immune system may ease IBD, but raise the risk of infections.

Around 2 million people worldwide take anti-TNF drugs, which are known to impair immunity following vaccination against pneumonia, flu or viral hepatitis.

The medications are also linked to a higher risk of infection complications, particularly those affecting the airways.

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IBD patients were therefore told to shield or be particularly cautious amid the pandemic.

To learn more, the Royal Devon medics analysed more than 6,900 IBD patients – average age 39 – who took part in the CLARITY study. The patients were recruited from 92 hospitals between September and December 2020.

Nearly 40% of the patients had been swabbed for the coronavirus, with infection rates being similar between those on infliximab or vedolizumab, at just over 5% and 4%, respectively.

Of the infliximab patients with the coronavirus, just under half (48%) subsequently developed antibodies, versus more than four in five (83%) on vedolizumab.

Antibodies help fight off an infection. The proteins then circulate at low levels in the blood, preventing the virus from taking hold again.

When infliximab was combined with other anti-inflammatory drugs, like thiopurine or methotrexate, only a third had detectable antibodies against the coronavirus.

Raised antibody levels were observed four weeks after a positive coronavirus swab in those on vedolizumab, but not infliximab.

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"Similar rates of symptomatic and proven [coronavirus] infection and hospitalisations between infliximab-treated and vedolizumab-treated patients suggest our findings cannot be explained by differences in acquisition or severity of infection alone," the medics wrote in the journal Gut.

"Rather, infliximab seems to be directly influencing the serological response to infection.

"Infliximab may directly impede the immune mechanisms responsible for generating antibody responses."

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The medics stressed their study was observational, and therefore does not prove cause and effect.

A weakened immune response in infliximab-treated patients does not necessarily raise the risk of infection, they added.

The immune system is also not just made up of antibodies, with the medics yet to reveal how infliximab may impact infection-fighting B or T cells.

The only anti-TNF drug the team looked at was infliximab, with the results not necessarily applying to other medications of the same class.

Nevertheless, a weakened antibody response could increase susceptibility to recurrent infections.

The coronavirus may also colonise an IBD patient's nose and throat, "acting as a reservoir to drive persistent transmission and the evolution of new variants".

The medics are calling for infliximab-treated patients to be monitored after a coronavirus vaccine to ensure a strong antibody response has been mounted.

“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 [the coronavirus] infection and COVID-19," said Professor Ahmad.

"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."

Sarah Sleet – CEO of the charity Crohn's & Colitis UK – agreed, adding: "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.

"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."

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