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Improvements With Guselkumab in Psoriatic Arthritis Seen Across All MDA Domains

— Experts discuss importance of both physician- and patient-reported domains

MedpageToday

At the American College of Rheumatology annual meeting, results from the were presented that examined the association between patient- and physician-reported domains and minimal disease activity (MDA) achievement for psoriatic arthritis patients treated with guselkumab (Tremfya) after an inadequate response to tumor necrosis factor (TNF) inhibitors.

In this third of four exclusive episodes, 鶹ý 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 new findings from the COSMOS trial.

Watch other videos in the series here.

Following is a transcript of their remarks:

Husni: So I do want to end with two other abstracts that are a little bit different. One, Tony, I wanted to talk to you about the COSMOS study and then Len, I was going to talk to you about a biomarker study. But let's start with COSMOS, which is abstract number 1421.

So in addition -- we talked a lot about skin efficacy and joint efficacy -- so what this COSMOS study was looking at [was] guselkumab and what they did in this TNF inhibitor-inadequate-responder group is that they looked at something called minimal disease activity. And I know that's maybe more of a rheumatologic outcome, but what they're saying in this abstract is that there are a lot of patient-reported sort of MDAs that aren't domains that are less frequently achieved than just skin and joints, what we care about in the bigger RCTs [randomized controlled trials].

So this phase III study showed that with guselkumab compared to placebo, that they really have sustained improvement in all areas of MDA. So not just joint and skin, but enthesitis, HAQ [Health Assessment Questionnaire] scores, our patient pain scores as well. And so I was just hoping you could comment, in [dermatology], are you looking at these domains outside of skin? Does it matter when you're treating your patients?

Fernandez: That's a great question. I think mainly in dermatology we're looking at patient-reported information, but mainly as it relates to the skin. So itching, pain, things like that. And I know minimal disease activity looks at sort of broader patient outcomes. I guess patient pain, but more on a global scale as opposed to just related to the skin.

But I think the data in this study is really interesting. And I guess the first thing that pops into my mind is that we definitely need to make sure that we pay attention to the patient's point of view and how the patients feel these medications are working for them and not just use our own assessments, number one.

Number two, I know for guselkumab, for psoriatic arthritis, there's data about fatigue, which I know is this multifactorial problem and there seems to be something about guselkumab, maybe other interleukin-23 inhibitors, that may be able to address that fatigue that other classes of biologics have not been able to address. And I wonder if that correlates with why these patient-reported measures that are part of MDA improve so well in the COSMOS study.

Husni: Yeah, I like what you said. I think we're sort of raising the bar. We used to say, OK, skin clearance, joint improvement, but now we're talking about these other domains and I know Len and I talk a lot about fatigue.

I have to say Len, when someone has active joints, I have a path in my mind, or active skin. But when they say I have more fatigue, I don't know if I know that path and what to do if I would actually switch patient drugs or provide them with other techniques to help with their fatigue. What are your thoughts on your path to treatment for fatigue?

Calabrese: I think every single immune-mediated inflammatory disease follows the model that the great group at Duke has outlined for lupus. Type 1 is active inflammatory disease. Type 2 is a lot of quality of life measures with well-controlled disease. And that is not minimizing it. It's recognizing it that in all of our IMIDs [immune-mediated inflammatory diseases], the domains of pain, fatigue, neurocognitive dysfunction, and sleep are overexpressed.

So psoriasis, psoriatic arthritis fit in that club, and I think that this is a call to separate out patients that really have poorly controlled inflammatory disease and may benefit from biologic manipulation versus those that need much more in the way of holistic care, which is now thankfully finally after a long time, rising to the fore as a necessary part of our treatment.

Husni: Yeah, well said. So I don't know, Tony, are we going to be seeing Type 1 and Type 2 psoriatic diseases?

Calabrese: Everyone.

Fernandez: I think we need to -- rheumatologists, dermatologists -- I think we need to really consider that and evaluate our patients to see if that's a good way to categorize them. I agree, what Len said was very well put, and I think we can rationalize that we all see patients who fit into one of those categories. So yeah, no, I think it's...

Calabrese: The work from Duke in lupus is at the forefront of this. I mean they've done this in terms of both quality of life measures, but at the transcriptomic level, these patients are different. And I mean it's different biology going on here. We shouldn't expect to just keep switching drug to drug to drug. I think we need to get a little smarter here.

Husni: Yeah. So one size doesn't fit all.

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