The rate of progress in IBD is staggeringly fast.
I see this in clinical trials, basic science and translational research. I see progress across all sectors from patient organisations to academia and industry. There is substantial investment of people, time and money. Research and development spending in BD is substantial and growing.
Some breakthroughs will take many years before they translate to the clinic; others will fail. However much recent progress is already impacting on patient care and driving improved outcomes.
10 reasons why i'm hopeful about the future
There remains an urgent unmet need for people living with IBD today.
However on World IBD Day a message of hope is warranted. Hope can be a powerful drug. These are just some of the areas where I see rapid progress and reason for optimism.
1. Awareness and standards of care are improving across the world
A big investment in education and expansion of clinical teams has driven up standards of IBD care in many places. Awareness is improving across society thanks to the efforts of patient advocates and organisations.
2. Better access to effective therapies due to biosimilars
Biosimilar infliximab and adalimumab have >90% penetrance in most global markets for IBD, with the notable exception of N America.
The cost of these drugs is now almost comparable to mesalazine therapy. Reduced costs means improved access for patients. The strategy of early effective therapy in Crohn’s disease is now feasible for the majority of patients who need it. Drug dosing can be optimised early to achieve optimal drug levels, minimise immunogenicity and reach treatment targets.
3. Widespread adoption of effective monitoring strategies
Calprotectin testing is now almost universally available and in many countries has been rolled out to primary care. It is not a perfect test, nor particularly user friendly, but it is very helpful as a sensitive measure of gut inflammation.
Point of care monitoring with intestinal ultrasound is growing in popularity with clinicians and patients, although adoption remains very patchy in some reasons.
4. Multiple new therapies are reaching the clinic this year
Ozanimod is a sphingosine-1-phosphate (S1P) modulator which is FDA and EMA approval for the treatment of UC.
Filgotinib and upadacitinib are both JAK1 selective inhibitors. Filgotinib has had EMA approval for the treatment of UC and recently NICE and SMC approval in the UK. Upadacitinib has met all key endpoints across phase 3 induction and maintenance studies in both UC and Crohn’s disease.
Risankizumab is a humanised IgG2 monoclonal antibody targeting p19 and thereby specifically inhibiting IL-23.
5. The drug pipeline is deep, with many intriguing new targets
Slightly further down the line are further IL-23 mAbs (mirikizumab and guselkumab) and etrasimod (an oral selective S1p1, S1p4 and S1p5 modulator.
Novel targets in earlier stages of clinical testing include TD-1473 (Izencitinib; a gut specific pan-JAK inhibitor), SHR0302 (a JAK1 selective inhibitor), PF-06700841 (Brepocitinib; a JAK1/TYK2 inhibitor), PF-06651600 (Ritlecitinib; a JAK3 inihibitor), BMS-9861165 (Deucravacitinib; a TYK2 inhibitor), and ABX464 (oral small molecular that interacts with cap=binding complex).
Many therapies targeting the gut microbiome are in development and interventional dietary trials are yielding useful insights (e.g. DINE-CD).
6. Combination strategies show early signs of promise
The VEGA study presented at ECCO2022 was a phase 2 RCT exploring the effect of anti-TNF therapy (golimumab) plus anti-IL23 therapy (guselkumab) combined versus either therapy on its own. It demonstrated marked superiority of combination therapy on clinical response, remission and endoscopic improvement at week 12.
Further biosimilar molecules (notably for ustekinumab and vedolizumab - both coming within a few years) will potentiate the blocking of multiple inflammatory pathways at a reasonable cost.
7. New omics platforms incl. single cell sequencing are powerful
Precision medicine has failed to deliver meaningful, clinically actionable discoveries in IBD yet. Predicting outcomes has necessitated a dynamic approach contingent on serial sampling. However, this may all change thanks to several large scale single cell sequencing and associated bioinformatic pipelines.
8. Al. will transform the utility of endoscopy, histology and imaging
The first major application for A.I. will be fully automated scoring systems that will transform reporting in routine clinical practice and in clinical trial. This is already within reach with ulcerative colitis.
Next will be newer and better scoring systems that have true prognostic ability. A huge amount of hidden data with high-def video, digitised pathology and imaging will be unleashed. This could happen sooner than many expect.
9. Digital & clinical decision support tools to hyper-personalise care
Digital tools that allow passive frictionless disease and health monitoring with embedded dynamic prediction tools are being explored. They may be some way off yet in IBD, unlike in diabetes where continuous glucose monitoring has been enabled this already.
10. The threat from the pandemic to our patients has largely abated
The co-ordinated and large scale efforts from the IBD community have provided much reassuring data about the risk of severe COVID outcomes in IBD patients and with commonly used medicines. The attenuated response to vaccines in patients taking anti-TNF therapy has largely been overcome by booster doses and anti-virals.