World IBD Day 2023: Bridging Hope and Reality in the IBD Landscape

Dear Atomic IBD Community,

On this World IBD Day, it's time to take stock of where we stand in the battle against inflammatory bowel disease (IBD).

From the busy halls of the IBD clinic, it's clear that we're looking at a mixed bag in 2023. Hope and optimism certainly have a place, but there's no denying the challenges we face.

IBD awareness is on the rise worldwide, a trend that we should celebrate. But while the standard of care is improving, there's a long way to go. Resources are stretched thin, and although some local areas have made strides in equal care, there's a stark disparity on the global scale.

In this year's letter, we're getting real about the state of IBD care and research. We'll highlight the progress we've made, the hurdles we're up against, and the work still needed to ensure everyone affected by IBD gets the care they deserve.

Let's continue to push for improvements, share knowledge, and strengthen our community. Together, we can make a difference.

The therapeutic toolkit in 2023

The new therapies entering the clinic today

I am noticing a transformative effect of new therapies in my IBD clinic today.

Notably, the increased use of JAK inhibitors for both UC and Crohn's disease is shifting treatment paradigms. These effective medications, like upadacitinib, are making tangible improvements in patients' lives and present a promising outlook.

With JAK inhibitors we have orally delivered drugs that work fast and maintain efficacy after TNF failure.

However, they're not without drawbacks – they don't work for everyone, and side effects can occur.

Other promising treatment avenues include p19's (first up are risankizumab for Crohn’s disease and mirikizumab for UC) and S1pPs (ozanimod and etrasimod).

I’m optimistic about the drug pipeline

Two novel targets, TL1A and TYK2, backed by robust genetic data, are generating a lot of excitement in industry circles.

Prometheus's TL1A antibody, PRA0233, has had positive phase 2 data in Crohn’s disease and UC, triggering an acquisition by Merck (over 10bn dollars according to the press release ).

Several TYK2 inhibitors are currently in development. Whilst deucravacitinib failed phase 2 testing in UC, two further molecules show promise - VTX958 from Ventyx Biosciences and TAK-259 from Nimbus. Takeda recently completed acquisition of Nimbus in a 4bn dollar deal following positive phase 2b data in psoriasis.

I’m hopeful that we will continue to see major developments in this space over the coming 12 months.

The expanded use of existing drugs is improving outcomes

Eight years of biosimilar anti-TNF in the UK and across Europe has transformed our ability to get effective drugs to people when they need them.

That means early therapy in Crohn’s disease and expedient management of flares in ulcerative colitis.

Add JAK inhibitors and effective systems of care into the mix and the impact becomes palpable. Our local data show falling surgical rates and hospitalisation in both Crohn’s disease and UC. An expanded IBD nursing team, IBD pharmacists, administrators and daily flare clinics have made a huge difference locally.

Early next year we have biosimilar ustekinumab to look forward to.

We are expecting two USTE molecules in q1-2 2024 offering significant price reductions on the originator. However it isn’t clear how long it will take to get close to anti-TNF biosimilar prices. Using USTE first line in Crohn’s disease (as per SEAVUE) could come within reach in markets like the UK. Currently this is not a viable option for the vast majority of patients given the price disparity.

In contrast, Entyvio (vedolizumab) now has an extended runway out to 2032.

Monitoring Systems and the AI revolution

While the fundamentals of IBD monitoring haven't changed significantly in more than a decade, the future of this space looks promising.

Advancements like machine learning and AI integration into colonoscopy, pathology, and imaging could transform our approach within the next five years. Additionally, AI-powered digital tools could provide dynamic predictions and hyper-personalised management plans.

Will these technologies automate existing scoring system?

I think so, and this offers the opportunity to standardise care and improving reporting for both everyday clinical practice and clinical trials - reducing costs and barriers to entry.

Will we soon seen new AI based scoring systems?

Probably, and I think this will enable efficient longitudinal tracking of individual patients over time.

Will this enable true prognostication - ie a digital biomarker?

My feeling is yes. But this requires major investment. Big longitudinal cohorts with multi-modal data inputs and robustly definitely outcomes over time. If we can generate these data inputs to train the algorithms, we can expect transformative tools. Use of existing, retrospectively generated data, will likely be insufficient.

Holistic care is becoming increasingly important in managing IBD.

While we're making strides to meet patients' needs, we must continue to prioritise this approach, especially given the complexity of care required by older patients with multiple co-morbidities.

This World IBD Day, EFCCA's survey on IBD in older people highlights the importance of this topic.

Novel Biomarker Discovery and Precision Medicine

Biomarker discovery in IBD has been slow, but there are reasons to remain hopeful.

Large scale single cell transcriptomic studies and microbiome profiling could provide crucial insights into predicting treatment response and disease flare. The Curtis Huttenhower lab's recent discovery of microbial acetyltransferases that deactivate 5-ASA moieties (see Mehta et al Nature Medicine 2023), for example, may offer new avenues for personalised microbial therapies.

Studies like the IBD Response Study, led by Chris Lamb in Newcastle, and our own PREdiCCt study are at the forefront of these explorations.

Prediction of IBD onset and prevention

We are working on a roadmap towards prevention of IBD.

This will not be quick, but the GEM study led by Ken Croitoru, the PREDICTS study (Jean-Fred Colombel) and the PREDICT Centre for the Molecular Prediction of IBD (Tine Jess in Copenhagen) are shining a light on the pre-clinical phase of Crohn’s disease and UC.

It seems highly probable that we will be able to discovery reliable biomarkers of subsequent IBD development in at least a proportion of patients.

It is not yet clear how successful such a strategy will be:

• How soon prior to diagnosis will testing become reliable?

• What will the positive and negative predictive value be?

• And what if anything will we be able to do to intervene?

But at last we are having these conversations and learning from early data coming the right kind of cohort for this big problem.

Looking Ahead: IBD Care in 2023 and Beyond

As we look back on another World IBD Day, it's clear that our understanding of this complex disease, and our ability to treat it, is advancing rapidly. The landscape is changing, bringing with it a blend of optimism, caution, challenges, and opportunities.

The advent of new therapies, especially JAK inhibitors, is a cause for optimism. They are not only transforming patient care but also reshaping our expectations of what's possible in IBD treatment. However, it's crucial that we continue to improve their safety and efficacy, ensuring they offer a viable and tolerable treatment option for all patients.

The evolving therapeutic toolkit reflects our determination to provide more effective treatment strategies for patients. However, it's essential to recognise the uneven terrain we are navigating. While treatment options are expanding, their accessibility and effectiveness vary widely. Moreover, our healthcare resources are stretched thin, making it a pressing priority to advocate for better resource allocation in IBD care.

The promise of emerging technologies, such as AI and machine learning, in improving disease monitoring is an exciting prospect. Yet, this optimism is tempered by the recognition that these tools still need to be refined and scaled up to truly transform routine clinical practice.

We're seeing a much-needed shift towards a more holistic approach in IBD care, but we can't rest on our laurels. We must continue to focus on addressing the unique and complex needs of each patient, particularly those with multiple co-morbidities.

Despite the many challenges in the path of biomarker discovery, we're hopeful. The on-going research could hold the key to unlocking precision medicine for IBD, delivering truly personalised care to our patients.

As we move forward, let's view this World IBD Day as a call to action. Let's continue to push boundaries, question assumptions, and foster collaboration. We must remain committed to our shared goal: improving the lives of those living with IBD. The journey may be challenging, but the possibilities are immense. Together, we have the potential to truly change the narrative of IBD.

Here's to another year of progress and hope.