乌鸦传媒

At the American College of Rheumatology (ACR) virtual meeting, new data were presented on deucravacitinib (Sotyktu), a highly specific tyrosine kinase 2 ( TYK2) inhibitor that has been approved for patients with plaque psoriasis. In this phase II study, deucravacitinib achieved states of low disease activity or remission over a 52-week period in patients with psoriatic arthritis (PsA).

In this last of four exclusive ACR Expert Roundtable episodes, 乌鸦传媒 brought together three expert leaders in the field. Moderator , of the Oregon Medical Research Center in Portland, is joined by , a clinical researcher from Peterborough, Ontario, Canada, and , of Case Western Reserve University in Cleveland, for a virtual discussion on the .

Following is a transcript of their remarks:

Blauvelt: Hello everyone. My name is Dr. Andy Blauvelt. I'm a dermatologist and president of Oregon Medical Research Center in Portland, Oregon. This is a large clinical trial center, I also have a lot of experience taking care of psoriasis patients with and without psoriatic arthritis. Joining me today are Melinda Gooderham from Peterborough, Canada, who also runs a large clinical practice and clinical trial center, and Dr. Neil Korman from Case Western Reserve University in Cleveland. Welcome to the two of you.

So I think we're gonna continue the discussion into the next drug because I want to switch over to another type of JAK [Janus kinase] inhibitor called deucravacitinib. And here, we know that there are four types of JAKs -- JAK 1, 2, 3, and then a fourth one called TYK2, or tyrosine kinase 2.

And they're all involved in cell signaling, and so they all inhibit sort of a family or a group of cytokines, but each JAK is associated with different cytokine inhibition or cytokine signaling. And then each type of JAK is involved in different types of biologic processes. And the whole idea with deucravacitinib is to make it more selective and more safe than the classic JAK inhibitors by avoiding inhibition of JAK 1, 2, and 3 and just going to this other type of JAK TYK2.

And there you see actually a smaller number of cytokines that are utilizing that particular enzyme. And so what we see actually is a different safety profile, I think, with that drug, unlike kind of what's been described with the other classic JAK inhibitors.

So in the abstract that was presented at ACR, we have deucravacitinib for psoriatic arthritis, and here it's phase II right now and it's week-52 results that were reported at the meeting. And there are different doses studied -- six milligrams versus 12 milligrams -- and basically they had reported out earlier the efficacy and earlier time points. And then they found that patients continued to do well or improve from week 16 to week 52.

So that's kind of the main summary of the trial, so promising data for this new TYK2 inhibitor in PsA.

So let's go to Melinda, and tell me what you think about deucravacitinib, kind of in general and maybe for PsA.

Gooderham: Yeah, I really have a spot in my heart for TYK2 inhibition because of the safety that comes along with the efficacy. And as you mentioned, very few cytokines are using TYK2 compared to JAK1, which is used by many.

Deucravacitinib also has the added benefit of being an allosteric inhibitor, not a competitive inhibitor, which makes it even more selective. So we don't see the laboratory changes that we see with other JAK inhibitors. There's no cytopenias, no elevation in cholesterol. We still do see the odd CK [cytokine] spike, but it's not related to clinical sequelae.

So I really like that TYK2 mechanism, and I think it targets [interleukins] 12 and 23. The only thing that it does also target is the type 1 interferon. So you still can get an increase in viral infections that we see with JAK inhibitors, but as I mentioned, we can manage that with antivirals, with vaccination, with something like Shingrix [recombinant zoster vaccine]. So I think it's manageable, but I'm excited for this molecule.

Blauvelt: Great. And we know in the trials for psoriasis it was compared to apremilast [Otezla] and it clearly beat apremilast. So we have a better drug now for psoriasis, but I don't have a sense yet of deucravacitinib for PsA. It's hard for me to know that.

Neil, do you have any comments about this drug as far as where you're seeing it fit in or what you think of the PsA data?

Korman: I think the PsA data looks nice. I think the key here is that patients talk to us, we tell patients, "Okay, you need a systemic approach and so we're gonna get you on one of these shots, on one of these biologics," [and they say,] "Oh, I don't wanna take a shot, doc, can't you give me a pill?" And I just shut them down right there. I say, "no, there are no pills. There are no pills that will give you the results you want." And I just move on. And now I won't move on in those patients.

I mean, I don't think that its efficacy is a home run, but its efficacy is good enough that it's in the discussion. And I think it's very nice. I think it's a very nice option and I think our patients will definitely like this option and we'll take it up. And I think that it's probably for the person who maybe has a little milder disease; it's not for your most horrifically severe.

Blauvelt: Yeah, it's interesting. There's a natural experiment where people have TYK2 mutations and it's dysfunctional and they actually are relatively protected against psoriasis, psoriatic arthritis, and actually some other autoimmune disease.

So we may see this drug popping up not only in psoriatic conditions, but maybe in lupus, maybe some other autoimmune diseases, as it might be tested as well. So it's probably a lot more to come for this particular mechanism.

So Melinda, are you also doing trials with new TYK2 inhibitors? I know that...

Gooderham: Yeah, and they're working well in psoriasis. That's what, like you I don't have a full feeling about the PsA, but I think we're blocking -23 with this drug, so it should be working. And the phase II data looks great. Hopefully phase III pans out, but I think that that TYK2 target is a good one.

Blauvelt: Well, I want to thank you both very much for joining me today to discuss these new abstracts from the ACR meeting. I enjoyed it, I learned some things, and hopefully our listeners, our viewers, learn some new things from the ACR meeting and some new data on psoriatic arthritis.

Watch episode one of this series: Safety and Efficacy of IL-17 Blockers for Psoriatic Arthritis

Watch episode two of this series: IL-23 Inhibitors for Psoriatic Arthritis

Watch episode three of this series: Upadacitinib Versus Adalimumab in Psoriatic Arthritis

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