Developing ways for doctors to deliver more personalised treatment

2018

2018 


We hope to enable safer, longer-lasting, and more cost-effective anti-TNF treatment, by developing a new way for doctors to treat patients

Dr Tariq Ahmad
University of Exeter

What is this research looking at? 

Infliximab (known by brand names such as Inflectra, Remicade or Remsima) and adalimumab (also known as Humira) are anti-TNF drugs, used to treat patients with moderate to severe active Crohns Disease (CD) and ulcerative colitis (UC).  They work by blocking a protein called tumour necrosis factor (TNF).  TNF causes inflammation as part of the normal immune response. However, in people with CD and UC, TNF is overproduced, which causes chronic inflammation.  

Overall, these drugs are very effective at reducing inflammation and improving symptoms, but over time, they stop working for many people.  One of the main reasons they stop working is because people develop an immune response to the drug.  The body sees the drug as a potential threat rather than a medicine, and produces antibodies against the anti-TNF drugs. These antibodies stop the drugs from working and can cause side effects such as skin rash, difficulty in breathing, and low blood pressure.  

To reduce the risk of forming these antibodies, many people are also treated with an immunosuppressant drug, such as azathioprine or methotrexate.  These drugs can also cause side effects, and using two types of different drugs can increase the risk of infections, as the immune system is further suppressed compared to using one drug alone.  It is currently unknown why some people develop antibodies against anti-TNF drugs while others can successfully remain on the treatment for years with no formation of antibodies.  Initial research in this area suggests that genetics may play a role. 

The researchers are aiming to enable safer, longer-lasting, and more cost-effective anti-TNF treatment, by developing a new way for doctors to treat patients.  The ability to predict which people are more at risk of developing unhelpful antibodies before starting medication, could allow more personalised treatment.  Those at high risk would receive immunosuppressive drugs in addition to anti-TNF treatment, while those at low risk may receive anti-TNF treatment only. Furthermore, the research will lead to predictions in who may develop side effects to anti-TNF treatment so that they can be avoided in those at high risk. 

To achieve this, the researchers will use data and specimens already collected as part of the UK PANTS study and IBD BioResource, with three specific goals in mind: 

  1. Explore the best ways to measure antibodies to anti-TNF drugs. 
  2. Investigate factors specific to the patient and treatment that may predict an individual’s risk of developing immunogenicity – the production of antibodies against the drugs. 
  3. Improve existing methods and explore new treatments to reduce this risk. 

What do researchers think this could mean for people with IBD? 

The researchers hope to: 

  1. Develop a predictive decision tool for doctors, to help them choose the right drug or combination of drugs, to provide safer and longer-lasting anti-TNF treatment for people with Crohn’s Disease and ulcerative colitis. 
  2. Develop new, less immunogenic drugs.  
  3. Discover new therapies and improve old ones to reduce the risk of immunogenicity. 
  4. Define the necessity, best dose, and duration of anti-TNF and immunosuppressive therapies to prevent immunogenicity. 
  5. Develop the best treatment plan for people who develop immunogenicity.  

Who is leading this research:  Dr Tariq Ahmad, University of Exeter 
Our Funding: £120,000 
Duration: 36 months 
Official title of application: Reducing Risk, Improving Outcomes: Development of Personalised Strategies to Reduce the Impact of Immunogenicity to Anti-TNF Therapy