Immunogenicity to second anti-TNF
Research type
Research Study
Full title
Immunogenicity to anti-TNF therapy: implications for sequencing of anti-TNF therapy and choice of 2nd biologic
IRAS ID
257288
Contact name
Claire Bewshea
Contact email
Sponsor organisation
Royal Devon and Exeter Hospital NHS Trust
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
The anti-TNF drugs, infliximab and adalimumab, are effective treatments for patients with moderate to severe IBD when other treatments have not worked. They work by blocking a protein which drives persistent inflammation in patients, and successful treatment leads to healing of the gut, reduced hospitalizations and surgeries, and improvements in quality of life. Unfortunately, many patients lose response to these drugs over time and, in part, this is due to the development of an immune response to the drug (immunogenicity). Repeated administration causes the immune system to recognise the drug as a potential threat rather than a medicine, leading to the production of antibodies that block the action of anti-TNF drugs and increase the rate at which the drugs are removed from the body. We have recently shown that two-thirds of infliximab- and one-third of adalimumab-treated patients develop antibodies, and as a consequence, only half of patients who start an anti-TNF treatment remain on the drug at one year.
Questions and objectives: In patients who develop antibodies to their first anti-TNF therapy, current national and international guidelines recommend switching to another anti-TNF drug. However, it is not known whether patients who develop antibodies to their first anti-TNF drug are more, or less, likely to develop antibodies to their second anti-TNF drug. A greater understanding of the risks of forming antibodies to a second anti-TNF might help inform treatment choices. Therefore, we aim to define, in patients with IBD, treatment outcomes to second anti-TNF therapy, stratified by antibody presence to first anti-TNF therapy.
How it will be done: To answer this question, we will use results of antibody-testing carried out in the Royal Devon and Exeter NHS laboratory to carry out a UK-wide, multicentre, retrospective case-control study. First, we will identify all patients who have been treated with two anti-TNF drugs, and second, we will record treatment outcomes after each anti-TNF therapy. By linking existing therapeutic drug monitoring data (anti-TNF drug and antibody level) to pre-existing clinical data, we will be able to better understand the relationship between first and second anti-TNF therapy treatment outcomes.
Potential impact: It is hoped that this study will lead to improvements in the management of IBD and decrease suffering of patients. By better understanding the relationship between first and second anti-TNF therapies, doctors can avoid giving anti-TNF therapy in patients who are unlikely to have sustained benefit. Generating data on likelihood of success of drug sequencing in IBD may also help in the development of new drugs.
REC name
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REC reference
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