New Data on TYK2 Inhibitors for Psoriasis, Psoriatic Arthritis

Derick Alison
Derick Alison
9 Min Read

Studies were presented at the American College of Rheumatology (ACR) annual meeting on the safety and efficacy of two oral tyrosine kinase 2 (TYK2) inhibitors — TAK-279, a selective TYK2 inhibitor in patients with active psoriatic arthritis, and deucravacitinib (Sotyktu) for patients with plaque psoriasis.

In this first of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from the Cleveland Clinic — moderator M. Elaine Husni, MD, MPH, is joined by Leonard Calabrese, DO, and Anthony Fernandez, MD, PhD — for a virtual roundtable discussion about the two abstracts.

Following is a transcript of their remarks:

Husni: Welcome to this edition of MedPage Today. We’re going to give you updates from our American College of Rheumatology. And since I’m filming this during Thanksgiving week, I do want to say I’m thankful not only to my two guests who are here with me today, but just thankful that we were able to do an in-person meeting. It was really great to see all my colleagues that I probably haven’t seen in a bit, and I forget about the great interactions we have at these medical meetings. So I just wanted to give a shout out, grateful for my ACR for having it in-person, and we were in San Diego.

So I want to spend some time to introduce Dr. Len Calabrese and Dr. Tony Fernandez who work with me here at the Cleveland Clinic. I am Elaine Husni, a rheumatologist here. Len, you want to introduce yourself?

Calabrese: I’m Len Calabrese. I’m a rheumatologist and immunologist here at the Cleveland Clinic.

Husni: Thanks for being with us today. Tony?

Fernandez: Yeah, my name’s Tony Fernandez. I’m a dermatologist and a dermatopathologist here at the Cleveland Clinic.

Husni: Great. I share cases with these two all the time, so it’ll be interesting to see what they have to say about some of the new abstracts that we went through just a couple weeks ago in San Diego.

So I wanted to start with you, Tony, about [abstract] L12. Very exciting efficacy and safety outcomes of a selective oral TYK2 inhibitor that doesn’t even have a name yet — that’s TAK-279 for now — where they did a very early phase IIb trial in active psoriatic arthritis patients, a double-blind RCT [randomized controlled trial]. And so with this new oral TYK2 inhibitor, it showed good efficacy with skin with a moderate efficacy in joint disease. And I wanted to get your input in TAK-279, which has shown some good dose dependent efficacy over placebo, but only in 12 weeks.

Fernandez: Well, sure. We can start with the TYK2 inhibitor. I think this specific TYK2 inhibitor, to my knowledge, has not been studied solely in psoriasis. So I think the psoriasis data really comes from this study in psoriatic arthritis. But I’m sure as you know, Elaine, deucravacitinib is FDA approved to treat moderate-to-severe psoriasis in adult patients. And that is a selective TYK2 inhibitor similar to the medication mentioned in this abstract. And we’ve definitely had success with deucravacitinib. It is within the JAK [Janus kinase] inhibitor family, but because it is a selective TYK2 inhibitor, we think that gives it some very good advantages over other JAK inhibitors.

In terms of efficacy, in the pivotal phase III trials for psoriasis, deucravacitinib was able to achieve PASI [Psoriasis Area and Severity Index] 75 responses in somewhere between about 50% and 58% of patients by week 16. And in one of the studies as high as about 70% of patients at week 24. And PASI 90 response in about a third of patients by week 24. So it has good efficacy in those trials that went head-to-head with apremilast [Otezla] and was found to be statistically significantly better in terms of psoriasis response than apremilast.

And so that has meaning for a lot of clinicians who treat psoriasis and certainly for patients as well. So as our experience to date has been overwhelmingly positive with deucravacitinib.

Husni: OK, that’s interesting to hear. So I just want to jump over to Len abstract number 0261. This was looking at deucravacitinib in plaque psoriasis with their safety data. So we heard just from Tony a little bit about the efficacy. Just wanted to get your take on some of the 3-year safety data that’s coming out.

Calabrese: Yeah, you guys are psoriasis and psoriatic arthritis experts, and I live in a world of infections and immune diseases and very oriented to safety. So this is 3-year data. We’re not talking 3,000 patient-years. It’s not a lot, but it’s enough to kind of get some traction on what the safety signal looks like. And Tony alluded to that this is a JAK inhibitor, but it really doesn’t carry the labeling of a JAK inhibitor and hopefully is unencumbered by some of the baggage in terms of cardiovascular, oncologic, and infectious risks.

So this, after 3 years of study and getting a significant number of patient-years, it’s shown a couple things that I think are really promising. First, no new safety signals. The incidents of MACE [major adverse cardiovascular events] and malignancies was very low; deaths, nothing unexpected and untoward. And the thing that has been so interesting to us is this very modest [herpes] zoster signal, which is in distinction to non-selective JAK inhibitors. So, so far so good in safety with no surprises.

Husni: I just want to just remind us, at least in the RA [rheumatoid arthritis] world, regarding the oral surveillance studies that were done on the earlier JAK inhibitors and the somewhat pause that we have with the cardiovascular risks and thrombosis risks, and I guess we’re not seeing this in more of the selective newer TYK2 inhibitors.

Do either one of you change your management a little based on some of that oral surveillance data and some of these new…I know we don’t know in the whole class whether this is going to be a class effect versus individual drug effect.

Calabrese: I do. I mean, I think that non-selective JAK inhibitors aren’t great for older people that carry a lot of cardiovascular risk especially, or comorbid for other conditions. I think they’re an incredible class of drugs. They work in everything, but I try to reserve them for young and more uncomplicated people.

Husni: I agree. What about in the [dermatology] world, Tony?

Fernandez: Yeah, no, I agree a 100% with Lenny, as I think our knowledge of the JAK family and the signaling that’s mediated through those different kinases has taught us that a pan-JAK inhibitor can have broad effects, and the more selective we are then, at least on paper, the better the safety.

And I think so far we’re seeing that with deucravacitinib and that selectively inhibiting TYK2 has really resulted in a whole different side effect profile, a favorable one compared to previous pan-JAK inhibitors. And as Lenny mentioned, of course we need more data, but I think so far the data has supported that the selectivity can really be advantageous from a safety standpoint.

Husni: Yeah, good to hear. And it’s an oral option, which was also another nice plus.

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