Treatment principles in Crohn's disease: a graphical thread 🧵 (n~28)
There is lots covered here
• impact of CD
• early effective therapy
• surgical trends
• biosimilars
• head to head studies
• mucosal healing
Follow along below👇
Crohn's disease can have a significant impact on a person's life:
• physical aspects
• psychological aspects
• long-term complications of disease (and therapy)
• everyday life
We should remember this as physicians when we talk to our patients in clinic
This thread is based on a lecture I gave to the 1st annual BRICS IBD Symposium (Brazil - Russia - India - China - South Africa) last weekend
I recorded the talk which you can watch here
Unfortunately treatment failure and disease progression are common in Crohn's disease
• many patients have had Crohn's disease for a long time
• we have not always had effective therapies
• nor have we known to use therapies effectively until now
We are now in the multi-drug era for treating both Crohn's disease and UC
This is really the biosimilar anti-TNF era
This is the time when anti-TNF therapy should be affordable to all
And should not cost more than 2000 GBP per year
That changes everything
We know that Crohn's disease is progressive
Early in the disease course inflammation predominates
This is why early effective therapy works
The data from the anti-TNF studies shows this very clearly
This recent brilliant analysis by @ShomronH (individual patient level meta-analysis of RCTs) clearly shows the effect:
• in Crohn's disease the biggest benefit from biologics comes with a shorter disease duration
• BUT we do not see this effect in UC
• at diagnosis we need to predict risk of complicated disease
• we need to stratify therapy according to predicted response
However, we cannot yet do this ... therefore we must use a treat-to-target approach to monitor and adjust accordingly
Treat-to-target per STRIDE-2
The framework is simple
• set a target btwn physician & patient
• control symptoms; achieve mucosal healing; normalise QoL
• treat & monitor (CRP, FCAL + colonoscopy + MRI)
• if target not reached adjust therapy & proceed
Adalimumab early in the disease course with a treat-to-target paradigm
• mucosal healing rates of 45.9% at one year
• FCAL <250mcg/g most impt driver of Rx escalation
NOW a cost-effective option
We use ADA monoRx a lot for early Crohn's
SEAVUE - another early Crohn's disease study
Both ADA and USTE work really well
Excellent clinical remission and mucosal healing rates at one year
Better safety & PK profile for USTE
Importantly now we have many drugs that will heal the mucosa in Crohn's disease: IFX, ADA, USTE and VEDO of the licensed therapies
Most widespread definition is absence of ulcers
Mucosal healing remains THE treatment target in Crohn's disease
Anti-TNF drugs have been shown multiple times to be superb drugs to achieve mucosal healing
Nothing else could do this before they came along
We've had them >20 years now - only just starting to use them effectively!
USTE will heal the mucosa in Crohn's disease
The data from SEAVUE really add to this
VEDO also heals the mucosa in Crohn's disease
The data from VERSIFY (pictured) and CD-LOVE and VISIBLE 2 show this
The data on new molecules look very exciting too
The RIZA induction data show that mucosal healing is achieved by a significant proportion after induction only
The maintenance endoscopic data are even better
The drug works when anti-TNF have failed too - this is important
Soon we will also talk about effective dietary and microbiome therapeutics for Crohn's disease
I suspect for many these will be adjuncts to effective medical therapies
But for some they may be sufficient by themselves
We need much more quality research here
These slides are the basis of my talk on Crohn's disease: treatment principles and mucosal healing
It is recorded and uploaded here for you to watch:
Our team are working hard to produce many of these data
We are showing the benefit of
• biosimilars in IBD
• early effective therapy in Crohn's disease
• advance therapies in UC
• reduced surgical rates
• optimal use of T2T strategies based on FCAL
Lots more to come ..
Please leave comments below and go back to the top and share the first tweet ... this allows other to learn from the whole thread
• early effective therapy is key
• FCAL in year 1 is an excellent marker
• biosimilars make anti-TNF therapy an excellent option
• USTE & VEDO also good options for mucosal healing
• new therapies (esp anti-p19 eg RIZA) look superb
Game-changing small molecules that
• work fast
• work when TNF fails
• don't need steroids to work
Follow along as I outline the key themes 👇
JAKs are a family of intracellular tyrosine kinases
First discovered by Wilks in 1989
There are four JAKS - JAK1, JAK2, JAK3 and TYK2
They are the hub for >50 cytokine pathways
The biology is beautiful
When a cytokine bind to its receptor (eg IL-23 to IL-23R):
• ATP molecule binds to the JAK
• JAK transfers the PO4 from ATP to cytokine receptor
• STATs bind to this docking site on receptor
• the STATS get phosphorylated by the JAK
• STAT complex translocates to nucleus
🧵 covering:
• therapeutic targets
• treatment strategies
• therapeutic ceiling
• early effective therapies in Crohn's
• the pros and cons of anti-TNF
• new small molecules for UC