New findings from the team behind the CLARITY IBD study have shown that a drug commonly used to treat inflammatory bowel disease is associated with lower antibody responses to COVID-19 vaccines, as well as more breakthrough infections and reinfections.
Inflammatory bowel disease (IBD) is a term mainly used to describe two conditions: ulcerative colitis and Crohn's disease. Both are long-term conditions that involve inflammation of the gut. IBD is not the same as irritable bowel syndrome (IBS).
It is estimated that around 300,000 people in the UK have IBD, equating to roughly one in every 210 people.
There is no cure for IBD, but a range of treatments are available. In some cases, this may include immunosuppressants, where it is suspected that the immune system is a factor in a person’s illness. One downside to these drugs is that they increase the risk of serious infections and prevent vaccines from working fully.
Infliximab is a type of drug known as a biological therapy, and is used to treat a number of autoimmune diseases including Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis and psoriasis. Infliximab works by blocking a specific protein that causes inflammation in the body.
In this study, the researchers set out to assess if a third dose of an mRNA-based vaccine (Pfizer or Moderna) could substantially boost antibody responses and protective immunity in a group of 918 people treated with infliximab for their IBD. They compared the results for this group with another of 442 people treated with a different drug (vedolizumab). Their findings are published in the journal, BMJ – Gut.
They found that, when compared with people treated with vedolizumab, those on infliximab were more than twice as likely to get a breakthrough infection (where someone who is vaccinated catches COVID-19). This effect could not be explained by levels of antibodies after a third vaccine dose, and this is likely due to the fact that the vaccines are designed to generate antibodies to the original strain of the virus, and have limited effect against Omicron.
Antibody levels increased in both groups following a third dose of an mRNA-based vaccine, though these were lower in people treated with infliximab compared to vedolizumab, regardless of which vaccine type they had for their first two vaccine doses. The life-span of antibodies was also shorter in the group treated with infliximab. A fourth jab was not seen to substantially boost antibodies above levels achieved by a third dose in either group of participants.
Hospitalisations and deaths were uncommon in both groups.
The researchers concluded that a third dose of an mRNA vaccine gives substantial protection to people treated with infliximab, but that booster doses would need to be given every four to six months to maintain this protection, in order to counter the waning of antibodies over time.
The researchers stressed that the arrival of new variants of COVID-19 has meant that antibody testing is of limited use to assess vaccine effectiveness, as the antibodies produced target the spike of the original Wuhan variant of the virus.
In addition, it is possible that the immune suppressing effect of drugs such as infliximab may protect people from very severe COVID-19, as severe illness is known to be caused in some cases by a systemic inflammatory response. However, more work would be needed to confirm this theory.
This study was supported by UK Research and Innovation via funding for the as part of the DuRaCoV (Durability of immune responses to vaccination against SARS-CoV-2 and its Variants) study via funding for the National Core Studies Immunity Programme.