Dr Amera Elzubeir and Dr Simon Rushbrook (Norfolk and Norwich University Hospitals NHS Foundation Trust) have been given funding by the National Institute for Health and Care research to conduct a pilot study to investigate Brodalumab in the treatment of primary sclerosing cholangitis (PSC).

 

PSC is a rare liver disease where the body attacks itself, causing inflammation and scarring of the bile ducts and liver. This causes bile to stop flowing properly and in turn leads to repeated infections, liver failure, and in some cases, cancer. In 80% of people with PSC, the body also attacks the bowel, which can lead to development of a unique type of inflammatory bowel disease called PSC-IBD. People with PSC-IBD have an increased risk of bowel cancer compared to those with inflammatory bowel disease alone and therefore must have an annual colonoscopy to check for early cancer signs. Sadly, there is no proven treatment to slow down the disease, and for some, liver transplantation is the only lifesaving option. For these reasons, people with PSC urgently need a cure or effective treatment.

 

Recent research (from both animal and human studies) shows that the immune system is responsible for bile duct damage in PSC. The parts of the immune system that drive this damage are called T cells and B cells. Research has shown us that in people with PSC, these T cells release a chemical called Interleukin 17 (IL-17). Interestingly, this same process is important in other autoimmune diseases, such psoriasis (a skin condition) and certain types of inflammatory arthritis.

 

Importantly, powerful drugs called biologics that target specific parts of the immune system have already been developed to treat these diseases. One such biologic is Brodalumab. It is used for psoriasis and reduces the effects of IL-17.

 

Therefore, given the potential importance of IL-17 in PSC, we will study the effect of Brodalumab in people with PSC.

 

20 volunteers with PSC from four large PSC centres (Norwich, Oxford, Cambridge and Birmingham) will take part. They will all be given Brodalumab for 12 weeks (once a week for three weeks, then every other week). Brodalumab will be given using an injection pen and participants will be able to do this themselves at home after training.

 

We will monitor people who take part with blood tests, liver scans, a single colonoscopy and questionnaires. Participants will be followed up for a total of 6 months.

 

A group of ten people with PSC from across the UK helped the research team with the design of our study and highlighted the priorities and concerns of people with the condition. For example, the group felt that two colonoscopies might put people off, as they already need to have one annually. Therefore, we will use the results of participants’ most recent colonoscopy so that only one additional colonoscopy is needed to take part.

 

If the results of this study are promising, then we hope to build on our findings and replicate them in a larger study (randomised control trial).

 

Patient experts from PSC Support will join our Trial Steering Group, and a group of PSC patients, led by PSC Support and the Primary Investigator, will meet virtually at key milestones to help develop patient facing materials and give vital feedback for the duration of this study.

 

The study will commence in Autumn 2022 and begin recruiting participants in early 2023.

 

Dr Amera Elzubeir is a gastroenterology registrar in her final year of training with an interest in autoimmune liver diseases, specifically PSC and its association with IBD. Dr Elzubeir is delighted to have been awarded funding by the NIHR to undertake a 3-year PhD at the University of East Anglia, delivering this vital study investigating brodalumab in the treatment of PSC.

 

Dr Elzubeir said, “Brodalumab and its family of drugs have been safely and successfully used in patients with skin and joint conditions, proving to be an effective treatment. We recognise that trialling medications such as these, already studied and approved in other conditions, represents a unique opportunity to build on what we already know whilst tapping into this potentially rich and emergent source of safe and effective treatments that may be beneficial for conditions such as PSC”