Yesterday I addressed the Crohn’s Colitis UK Annual General Meeting in a pre-recorded video. You will find a transcript of the video below.
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Introduction
Hi there, Charlie Lees here – gastroenterologist, professor of gastroenterology at the Edinburgh IBD unit.
It's Thursday evening, and I’ve just come out of today’s IBD clinic with our excellent team. I've been thinking about how our patients have been today. Many are doing very well now, but some are clearly still struggling a bit, through symptoms or ongoing inflammation, troublesome quality of life, or other issues that we’re doing our best to manage.
Reflecting on the Current State of IBD
It’s September 2024, and I thought it’d be useful to reflect on where we are just now.
From a clinical point of view and through research, what we’re understanding, and where our big gaps are in addressing these issues in the UK and beyond as we move forward.
Epidemiology
We’re really at an almost historic moment, where we understand more and more about the epidemiology of inflammatory bowel disease. Work from ourselves in Edinburgh, others around the UK, the Canadian team that’s been so influential here, and importantly, colleagues from both the developed and developing world, has shown that almost 1 in 100 people are living with inflammatory bowel disease.
By 2028, we’re expecting to reach that 1% mark.
So here we are – 400,000 to 500,000 people in the UK living with IBD at some point in their lives. And many of these people are getting older. Older patients often come with significant issues of their own, such as multimorbidity, polypharmacy, frailty, and other challenges. And while we’re still diagnosing most people young in life, we’re not undiagnosing anyone.
Crohn's disease and ulcerative colitis remain lifelong and incurable. For many people, as lots of you will know, they can be devastating and intrusive.
But with effective therapy and many of the new treatments we have, we can see very good and sustained results for the long term.
We’re also seeing new cases of IBD surging in other parts of the world. We're seeing this across South America, Southern and Far East Asia, the Middle East, and now sub-Saharan Africa. Projections over the next 10, 20, 30, even 50 years show that the majority of people living with IBD globally will be in currently developing countries.
As these countries industrialise and adopt a Western lifestyle, IBD cases surge.
Genetics, Diet, and the Environment
We understand the genetics very well. Our efforts, along with international ones, have genotyped over 100,000 patients, identifying over 650 points in the genome associated with IBD susceptibility. This gives us important clues about the underlying biology and potential drug targets. Many of the current drugs, like anti-TNFs, JAK inhibitors, and IL-12/23 inhibitors, have strong evidence based on genetics.
But genetics alone don’t explain the epidemiological shifts. What does?
We’ve seen data in the past years showing that early-life antibiotic exposure seems to be a key factor. New evidence about diet is also emerging. Recent studies show an association between ultra-processed food intake and Crohn’s disease – but not ulcerative colitis. That said, this doesn’t mean UPFs cause Crohn’s. Many people with Crohn’s have never eaten bad foods, so it’s not the sole culprit, but it’s a contributing factor.
We in Edinburgh have been very interested in the role of diet in disease flare.
The PREdiCCt study, with 2,500 participants from 50 UK sites, has provided fascinating insights. We’ve seen that eating too much meat increases flare risk in ulcerative colitis. Depression and lack of physical activity also raise the risk of flares, independent of inflammation levels.
Personalised Medicine and Digital Health
The future of IBD management is moving towards prediction and prevention.
With new data showing potential predictive markers, like antibody signatures or microbiome changes up to 10 years before a Crohn’s diagnosis, we’re getting closer to early detection. This opens the door to preventive strategies, whether through dietary changes, avoiding certain medications, or even treating high-risk individuals early.
There’s also a lot of excitement around personalised medicine.
Studies like the IBD Response Study and the IBD Open Study are leading the way in understanding how the gut microbiome might predict therapy responses. These large UK-wide studies are using cutting-edge technologies like single-cell sequencing to identify disease course predictors before patients even undergo their first endoscopy.
And then there’s digital health and AI, which are making huge strides in the field.
Predictive analytics, using big data to personalise patient care, and AI for colonoscopy images and pathology are transforming how we treat and understand IBD.
The Treatment Pipeline and Unmet Needs
In terms of treatments, 2024 offers a wide range of options. Biosimilar drugs like infliximab and adalimumab have been available for almost ten years, making these treatments more accessible. Newer drugs like ustekinumab are also becoming more affordable. J
AK inhibitors, like upadacitinib, are showing rapid results, often working within days, which helps reduce the use of damaging steroids.
We’re also seeing the introduction of new p19 molecules like mirikizumab for ulcerative colitis and risankizumab for Crohn’s and UC. These newer drugs are giving us more options, and the pipeline is looking healthy, with many promising drugs in phase two and three trials.
However, there is still a huge unmet need.
We have too many patients who aren’t doing well enough. Conditions like perianal fistulising Crohn’s disease and fibrotic Crohn’s disease still pose significant challenges. But research, like the Gondomar Study, is focusing on understanding these conditions better to improve treatments.
So, there’s a lot of hope and optimism.
The UK is at the forefront of IBD research, thanks to the leadership of the BSG, Crohn's and Colitis UK, and other key organisations. We’ve come a long way, but there’s still much more to do.
Are we close to predicting and preventing IBD?
No, but a roadmap is clearly emerging.
Are we close to a cure?
Also no, but we’re making progress.
Maybe one day soon, I’ll be able to come back with an exciting update on that front.
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