We have funded multiple studies run by the Exeter IBD and Pharmacogenetics Research Group – headed up by Dr Tariq Ahmad, Consultant Gastroenterologist at the Royal Devon and Exeter. Their work brings hope that personalised medicine is not too far into the future, and we want to help with these advancements which will allow the selection of the right drug, at the right dose, for the right patient, first time.
The current trial and error approach is just not good enough. It is stressful for clinicians and patients, and causes additional concerns because the treatment might not even be effective. Then there’s the side effects, adverse reactions, and the consideration of surgery if disease continues to progress. Plus, patients have the additional worry about the impact on quality of life whilst waiting for a treatment to work. Long flares can negatively impact all areas of our lives; from education and work, to family life and friendships. Then, there’s the psychological impact, which can leave people with IBD feeling frustrated, isolated, anxious and depressed.
This is why the work that the Exeter IBD and Pharmacogenetics Research Group are doing is so important. Studies so far have employed the latest genome sequencing techniques to identify predictive genetic markers of drug response and side effects.
The current study is a follow on from the Personalised anti-TNF therapy in Crohn’s disease (PANTS) study, which looked at the factors involved in why treatment fails so many people with Crohn’s disease.
The PANTS study showed that about a quarter of patients had no response to the drugs and in one-third of initial responders, the drug stopped working within the first year of treatment. Nearly 10% of people experienced adverse events that resulted in the treatment being stopped. Just 37% of patients starting anti-TNF drugs were well and still on treatment at the end of the first year.
The latest study we have invested 55K funding in is Immunogenicity to anti-TNF therapy: Implications for sequencing of anti-TNF therapy and choice of second biologic (IMSAT).
Roy Provan, Chair of Cure Crohn’s Colitis says: “I am very excited that we are able to fund world-class research such as this. This is an important step towards the personalised medicine we hope to see evolve in the future, to become part of standard practice in IBD care.”
The anti-TNF drugs, infliximab and adalimumab, are effective treatments for patients with moderate to severe IBD when other treatments have not worked. Unfortunately, many patients lose response to these drugs over time. 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.
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’s not yet known whether patients who develop antibodies to their first anti-TNF drug are more, or less, likely to develop antibodies to their second.
This study aims to define treatment outcomes to second anti-TNF therapy, in patients with IBD, stratified by antibody presence to the first anti-TNF therapy.
How it will be done
Results of antibody-testing carried out in the Royal Devon and Exeter NHS laboratory will be used to carry out a UK-wide, multicentre, retrospective case-control study. First, all patients who have been treated with two anti-TNF drugs will be identified. Second, treatment outcomes after each anti TNF therapy will be recorded. By linking existing therapeutic drug monitoring data (anti-TNF drug and antibody level) to pre-existing clinical data, the study team will be able to better understand the relationship between first and second anti-TNF therapy treatment outcomes.
It is hoped that this study will lead to improvements in the management of IBD and decrease the 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 a sustained benefit. Generating data on the likelihood of success of drug sequencing in IBD may also help in the development of new drugs.
Dr. Neil Chanchlani, clinical research fellow and study lead alongside Dr. Tariq Ahmad said: “I’m incredibly excited to work on this important project which aims to better understand the risk of patients with inflammatory bowel disease developing antibodies to anti-TNF medications, such as infliximab and adalimumab. The study is one of the largest of its kind, and the results will help guide treatment algorithms in the management of inflammatory bowel disease, including in whom to give anti-TNF medicine, or alternative therapy, to. The study team are appreciative of the collaborative efforts of the clinicians, research, and IBD nurses working across 45 UK sites to collect the data. We are also very grateful to Cure Crohn’s Colitis who are funding the study, without whom this would not be possible.”
Your donations made it possible for us to invest in this research! 100% of the donations we receive fund patient-centric IBD research, to improve the lives of Crohn’s Disease and Ulcerative Colitis sufferers, and to ultimately find a cure. We are run solely by volunteers to make this possible. If you would like to fundraise or donate so that we can invest in more IBD research, pop over to our website or Facebook!