Interleukin 23

In the Daily Roundup, Sun Pharma's Illumia now has FDA approval for adults with active psoriatic arthritis, a chronic, immune-mediated disease of painful, swollen joints.

Illumia is an IL-23 inhibitor already approved for plaque psoriasis.

This approval rests on its own arthritis evidence.

Two randomized, placebo-controlled Phase III trials in about 800 adults.

Every day, every month, Room Now publishes news and information on JAK inhibitors, IL-17s, IL-23s, lupus, myositis, scleroderma, all the stuff that could change your practice of dermatology.

I'm Jack Cush, executive editor of RoomNow.com, and this is a podcast for you, Derm on Room Now.

This week, the podcast will scratch the surface and find new drugs for dermatographism, hydradenitis, lupus, discoid lupus, and psoriatic arthritis.

for use in active psoriatic arthritis.

This extends its indication beyond moderate to severe plaque psoriasis, and the indication is going to be based on two very large phase three trials, INSPIRE 1 and 2, with over 800 patients in a 52-week set of studies.

That's good news for those of us who like the IL-23s.

It's getting to be a busy therapeutic area.

The FDA has also been active.

What they showed was for every 5% kilograms per meter square BMI, there was a 37% increase in the failure rate.

The lowest failure rate was seen with IL-17 inhibitors and IL-23 inhibitors, especially compared to TNF inhibitors, about a 50% lower rate compared to TNF inhibitors.

And again, obesity did not associate with secondary failures or toxicity failures.

I found that to be a new wrinkle, a And, you know, the problem with therapies in psoriasis, psoriatic arthritis is we've got a lot of them, yes, but we also have what I think are somewhat disappointing survival therapies.

And if you have a propensity, such as a patient who has a family history of atopic dermatitis or a family history of psoriasis, for example, then we have this propensity towards a specific type of pattern.

And therefore, we're going to see roles for cytokines like IL-23, which are helping get this naive T cell to become one of these high-producing cells that make signals like IL-17s, for example, which are going to give us that propensity for disease.

So this kind of lays out that you can look at the cytokine, like IL-12, IL-4, IL-23, as driving type 1, type 2, and type 3, respectively.

Or you can look at a transcription factor like STAT6, which which is critical to driving the differentiation to type two versus like stat three driving type two inflammation.

So as we learn these different signals, it helps us learn some of the soup, as you mentioned, that's helping push us towards a propensity for a certain type of an immune response, which tends to manifest in reproducible patterns.

And then type three, we tend to see more of the more classic hyper proliferative conditions like psoriasis, really classic there.

But we also start to see it play out in other conditions.

like some of the ankylosing spondylitis, for example, and even inflammatory bowel disease, which can have both a type three IL-23 component, but also a type one with a TNF and IL-12 component.

I should say, first of all, I have no problem continuing it if the disease activity warrants that we continue the TNF or JAK inhibitor for whatever reason.

If they're in remission and otherwise doing well from their inflammatory bowel disease standpoint and about to start chemotherapy, you could consider a switch to an IL-23, an IL-1223, or an anti-integrin.

But I've also had it the other way around, where either you have to go back to an anti-TNF or a JAK, or this is a person who's really not done well in these other therapies, and for their colitis or for their Crohn's disease, they really do need an anti-TNF or a JAK therapy.

And that's when it's really a discussion with...

Perhaps you know it's a lovely ancient city that is known because it's the end of the way.

I'm so happy to be here in the UEG in order to share with the gastroenterology community What we have done today, I've been the chair in the symposium about the use of guselcumab in UC, and I think that will be amazing, speaking about all this new data that is IL-23, it's true that it's a mechanical faction that I've been using in recent years, and we have observed that it's a very new mechanical faction, for patients, for example, that have failed TTNF.

Why? Because in that subgroup of patients, it has been shown that they have very good results, but also in Bionave patients.

One of the strengths of this drug, I think that is that they have a double induction regimen.

You can use intravenous, but it's the first IL-23 that we can use subcutaneous.

And you see something really different because with anti-TNF in the past, we have observed that patients treated with subcutaneous hazelis response rate.

But in this case, we have seen very high response rates and revision rates in patients treated with Gucel-Kumar.

And that's a target that we have achieved because of healing and we have proved in a study we have performed a long time ago that patients with MeO0, they are not going to develop symptoms in the following months.