51˶

Using Baseline Markers to Predict Response in Psoriatic Arthritis

— More biomarker research is needed, but new study is a good start

MedpageToday

In this final of four exclusive episodes, 51˶ 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 on the potential of finding baseline biomarkers to help develop precision therapies for psoriatic arthritis and other immune-mediated diseases.

Watch other videos in the series here.

Following is a transcript of their remarks:

Husni: So continuing this holistic approach and widening our domains of care and, what you said, rather than just randomly selecting drugs, are we a little bit closer to looking at baseline biomarkers to predict response? Len, I know that you've reviewed this abstract.

Calabrese: Yeah, I'll just start out by saying that across all of our diseases -- and I'll include psoriasis and psoriatic arthritis along with RA [rheumatoid arthritis] and lupus and any other disease that's treated with biologics -- we are woefully behind other diseases like oncology in developing precision therapies. We are not much different or well-off in any of these diseases than we were when any of these drugs were approved. Few things here for biomarkers for ANCA [antineutrophil cytoplasmic antibodies] and rheumatoid factor, et cetera, but very puny.

So anyway, . Phase II trial that was an RCT [randomized controlled trial]. So there's a placebo group, there's a TYK2 [tyrosine kinase 2] deucravacitinib [Sotyktu] group, and they looked at immunoassays to a wide panel of things that they hoped would really knock this out of the park. So deucravacitinib is a TYK2 inhibitor, so it knocks down IL [interleukin]-23, IL-12, type I interferon, and a whole associated group of cytokines.

At the end of the day, regardless of the analyses, people did better, even if they weren't enriched for the few biomarkers, which seemed to accentuate response. And not surprisingly, they were in the family of cytokines that are encompassed by that TYK2 pathway. So IL-17a, IL-19, and beta defense and type 2, which is intimately involved in barrier defense and IL-17 biology. I think it's a nice start. I don't think it's going to change our practice. But when will we be able to profile people through deep immunologic and/or genetic analysis and pick one of these dozens of biologics that we have versus what we do now?

Husni: Yeah, I think it's just really interesting to think of managing that patient expectation. I really try to tell them in advance that we have a lot of available treatments, which is great, but I don't know which one is going to work for you.

So now, I mean Tony, you have just as many to choose from in psoriasis and if you have any thoughts on predicting any baseline markers?

Fernandez: Well, I think as you mentioned, right now, we feel spoiled to have such great options, but I think our approach by and large is shared decision-making with patients because we cannot necessarily predict who's going to respond to what. But I think the idea of biomarkers, as Lenny mentioned, it's far more advanced in the oncology world than in the immune-mediated disease world. But studies like the one just mentioned are a great start and I do think there's great promise given what we know, these biomarkers and how they're used in oncology. I think there's great promise for the future where we can really provide some objective information to patients to suggest why one medication may be better for them than another. So I think there's a lot of work to be done and it's nice to see that we're moving forward in the area.

Husni: Yes, well put, we're still the art of medicine, not the exact science where you can maybe drive through a drive-through to get your biologic.

Alright, well, thank you so much for the both of you for your thoughts on this year's ACR [American College of Rheumatology] abstracts.

Calabrese: My privilege. Thank you.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.