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Mirikizumab

Impressive results on a phase 3 trial:


« At one year, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of patients on mirikizumab, respectively. Notably, of the patients who received mirikizumab, 56.7% of bio-naïve and 51.2% of bio-failed patients achieved clinical remission at Week 52. »
 
This is great news - I wonder, if someone would fail another IL23 inhibitor, like risankizumab, would they still have a reasonably good chance of reacting positively to this, because of the slightly altered mechanism - IL23p19 instead of IL23A ? Was wondering the same about ustekinumab vs risankizumab too, where its p40 vs A targeted mechanism. Very interested if failure of a drug in general is because IL23 is irrelevant in given patient's inflammation levels, or, is it that the given mechanism isn't inhibiting that specific pathway properly. Perhaps someone smarter than me could answer. So basically you could fail any of these 3 mentioned biologics, and have a reasonable chance to try another one and expect it to succeed.
 

Scipio

Well-known member
Location
San Diego
This is great news - I wonder, if someone would fail another IL23 inhibitor, like risankizumab, would they still have a reasonably good chance of reacting positively to this, because of the slightly altered mechanism - IL23p19 instead of IL23A ? Was wondering the same about ustekinumab vs risankizumab too, where its p40 vs A targeted mechanism.
The proof will be in the pudding as more anti-IL23 antibodies come online, but in theory one could lose response to one IL-23 antibody drug yet still retain it for another. We see that currently with the anti-TNF drugs. A patient may lose response to Remicade and yet Humira may well still work. In all cases, it may depend on the reason why the response to initial drug has failed. Some mechanisms of failure may carry over to drugs of similar specificity and others may not.
 
The proof will be in the pudding as more anti-IL23 antibodies come online, but in theory one could lose response to one IL-23 antibody drug yet still retain it for another. We see that currently with the anti-TNF drugs. A patient may lose response to Remicade and yet Humira may well still work. In all cases, it may depend on the reason why the response to initial drug has failed. Some mechanisms of failure may carry over to drugs of similar specificity and others may not.
Yes, intuitively I think that one makes a lot of sense and we do see that clearly in anti-tnf-s, you build resistance to a specific antibody and hence its part of clinical practice to offer another from the same class if it worked - what I am really curious about tho is if someone is a primary non-responder, or very limited responder, to an IL23 inhibitor, then could another still work. I am hoping for a "yes" as that would widen the group of people who have at least 1 medication option. With anti-tnf-s I think its generally really unlikely to respond to one at first, but not to another, but also, to respond to one when not to another. But in the end they are the inhibiting the same thing in a very similar way, while here there are some differences. So perhaps primary non-response often is from the "how" and not the "what". But haven't really found any data to prove / disprove my wishful theory.
 
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