Philip Mease, MD, on Assessing Treatment Response in PsA by Disease Domain

In this podcast, Dr Philip Mease reviews recent research on the importance of assessing treatment response across all domains of psoriatic arthritis, including skin, joints, entheses, and more.

Philip Mease, MD, is clinical professor at the University of Washington School of Medicine and director of Rheumatology Research at the Swedish Medical Center in Seattle, Washington.

TRANSCRIPT:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your host, Rebecca Mashaw, and I'm delighted to have the opportunity to speak with Dr. Philip Mease, who is clinical professor at the University of Washington School of Medicine and Director of Rheumatology research at Swedish Medical Center in Seattle. He's going to discuss his and his colleagues' research into real world evidence assessing Psoriatic Arthritis by disease domain, an evaluation of the CorEvitas Psoriatic Arthritis, Spondyloarthritis Registry. Welcome Dr. Mease, and thank you for taking the time to talk to us about this study.

Dr. Mease:

And thank you for having me, Rebecca.

Rebecca Mashaw:

Would you first start off by telling us a little about the CorEvitas registry?

Dr. Mease:

Yes. The CorEvitas Registry began its life in the early 2000s, started by Joel Kramer, a rheumatologist from Albany, New York, who recognized the need for a national registry of rheumatoid arthritis and psoriatic arthritis patients. It was known as the CORRONA Registry at the time, Consortium of Rheumatology Researchers of North America. What has happened over time is that it has grown exponentially and now involves other disciplines besides rheumatology, including gastroenterology with inflammatory bowel disease, psoriasis with dermatologists, and so on. So this is one of the reasons that led to the name change CorEvitas. Since 2013, partly based on my gentle nudging, we expanded the focus on psoriatic arthritis and the remainder of spondyloarthritis. And so we now have a dedicated registry for patients with psoriatic arthritis and axial spondyloarthritis since 2013. And I'm very involved in directing that particular arm of the CorEvitas registry.

We collect data on patients from around the United States in the PSA and AX Spa Registry, there are 64 sites, both private and academic that are contributing patients. And we now have over 7,000 patients in this registry. The Rheumatoid Arthritis Registry has nearly 50,000 patients involved, so we are able to get quite robust registry data from all of this.

Rebecca Mashaw:

Why did you decide to examine treatment response according to PSA domains?

Dr. Mease:

Psoriatic arthritis is a complex disease characterized by several different clinical domains, not only arthritis or the synovitis aspect of the disease, but also enthesitis, which is a specific problem where inflammation occurs where tendons and ligaments insert into bone like the achilles tendon or the plantar fascia. This is not typically seen in rheumatoid arthritis or many other forms of arthritis. Also something called dactylitis where a whole digit will be swollen and painful because of inflammation, not only of joints and enthesia, but also bone.

We also have in psoriatic arthritis spine involvement in about 40 to 50% of patients, and we call this axial PsA when present. And then of course, psoriasis, the skin disease, which is typically the first thing to be seen. And then over time about 30% of patients with psoriasis will develop psoriatic arthritis. Nail disease is very common, and then we sometimes see associated conditions like uveitis or inflammatory bowel disease.

So when we're comprehensively evaluating a patient with psoriatic arthritis, we really need to delve into each of these clinical domains because a patient may only focus on their arthritis or their skin disease, but not really think about, "Well, gee, come to think of it I've had rib cage pain, which could be enthesitis of the ligaments inserting into the ribs," or, "Gosh, I really am bothered by the achilles tendon, which just continues to be painful even though my joints and skin are fine."

And so it behooves us to be more holistic and cover all of these domains when we're evaluating patients and we're making sure that they're getting a complete treatment response.

Rebecca Mashaw:

Would you give us an overview of this particular research program, the numbers of patients that you looked at, the treatments that you evaluated and which domains were examined?

Dr. Mease:

We included about 1,000 patients who were initiating either a TNF inhibitor or an interleukin 17 inhibitor for the treatment of psoriatic arthritis. And we evaluated all of the domains that I just spoke about, particularly arthritis, enthesitis, dactylitis, spondylitis, skin and nail disease. And we wanted to see what were the patterns of involvement with these various clinical domains and how did the treatment with these different classes of biologic medications work in treating each of these domains.

Rebecca Mashaw:

And what did your findings show you?

Dr. Mease:

Well, the good news was that both the TNF inhibitor class and the interleukin 17 class, each was effective for these clinical domains pretty much across the board, whether it was musculoskeletal or skin disease or nail disease, all of them were effective.

Now, having said that, let's delve into a few details. So we found that about 80% or more of patients had arthritis and skin disease. About 60% had nail disease, about 40% had enthesitis, 25% had dactylitis. So as you can see, there was a bit of a spread of involvement of these domains with the most common being arthritis and skin disease. We also found that as patients were treated, the arthritis and skin disease improved in the great majority of patients. And at 6 months of follow-up, more than 60% of patients were still taking the treatment they started with, implying that these drugs were effective in treating these particular domains.

In the realms of enthesitis and spondylitis, we found that about 50% were still taking these drugs, suggesting that enthesitis and the back involvement with psoriatic arthritis might be just a slight bit tougher to treat. And some of the patients and their physicians were making the decision to switch over to different treatments. But by and large, I think the message was good, that across the various domains, these drugs were persistently effective.

Rebecca Mashaw:

Did you see any difference in how the IL 17 and the TNFI performed in specific domains, or was it again, as you say, pretty much across the board they both performed pretty well? But for instance, was IL 17 better at treating the skin disease than the TNFI?

Dr. Mease:

Well, that's a really appropriate question because many of us think about the IL 17s as being more effective in the skin because of the prominent role that interleukin 17 plays in the pathogenesis of skin disease. But in fact, what we found was that patients across the board we're getting good results. I think this also reflects the fact that for many of these patients, their amount of skin disease was not as great as what we see typically in a standard trial of psoriasis patients or registry of psoriasis patients. I think that the skin disease presenting to dermatologists in psoriasis patients tends to be a little bit more severe than the skin disease that we see. And so I think it's not a surprise that each of these drug classes was effective.

Rebecca Mashaw:

You mentioned in the article the heterogeneity of domains in PsA and how important it is to assess all of those to optimize disease management for these patients. How do you do this in your practice? Because you've talked about quite a few domains and there are quite a few ways to assess those and test them, and that's got to take some real time in the clinic. And as we all know, that time can be very limited these days.

Dr. Mease:

You're exactly right, and sometimes I will find that patients with psoriatic arthritis do take a little longer in the clinic than patients with a more unitary disease manifestation. But I do check through each of these. I ask about arthritis, I ask about enthesitis, I ask about skin disease and nail disease, and sometimes we'll find that they're not all moving in concert. So I liken psoriatic arthritis to a symphony orchestra, where at times, all of the sections are playing for fortissimo and it's important to try to get at all of them to bring this volume of sound coming from the orchestra down. But there may be times when, for example, just the clarinet section is playing and that's your single achilles tendon that stubbornly is not responding to treatment compared to the arthritis or skin disease.

So you've got to flag that and focus on it because that single achilles tendon pain may be hobbling, so to speak, the patient from being able to do their normal activities. And we may have to think about creative ways of and including bringing in, for example, foot orthopedist to help us with optimal management of some of these single issues, the single clarinet section that's playing.

Rebecca Mashaw:

And that brings up an interesting point. If the patient's doing very well in all the other domains, but that single achilles tendon is just refusing to cooperate, would you actually switch therapies or is this the ideal situation in which you might add another therapy?

Dr. Mease:

Again, a great question. So it's going to vary. First thing to do is to try to ascertain is this achilles tendon painful and not doing well because of ongoing inflammation that's not being controlled, and therefore it might make sense to either switch or add another therapy, or is there no evidence of inflammation and it is now a mechanical problem that may need a more orthopedic help. Well, for one thing, we might pull out the ultrasound machine and take a look to see if there is evidence of inflammation there to help answer that question. But if there is persistent inflammation, and if this is truly hobbling the patient from doing their best functionally, then we might switch to a different mechanism just to see if it will work. But sometimes in our clinic, we do use combinations of treatment, either adding in another biologic or targeted synthetic DMARD, an oral medication, for example.

The way we do this can be sometimes challenging. One way is to, for us as rheumatologists, to prescribe a certain medication, let's say a TNF inhibitor, and then a dermatologist might prescribe a different medication that's a biologic or tsDMARD such as an IL-23 inhibitor perhaps, or apremilast, which is a PDE4 inhibitor. And so we have 2 different disciplines prescribing 2 different medications. Sometimes insurance will allow us to do that, but many times they'll flag it and say, nope, can't do that. Can't have 2 expensive medicines going at the same time. And so then we sometimes will end up sampling the patient with a medication for a while. We have that capability in our clinic.

I should mention that all of this commentary about using a couple of medications in this way is off-label. We don't have clinical trials completed, although some are underway, which are testing the safety and efficacy of this approach. And it's very important for us to make sure that the patient understands that we need to monitor carefully for safety issues when we're doing this sort of thing.

Rebecca Mashaw:

How would you advise your colleagues in rheumatology to approach formulating treatment plans for patients? And this goes into what you were just saying and what we were talking about— but when there are specific phenotypes that are appropriately considered, how do you approach that? How would you advise others to approach that treatment planning?

Dr. Mease:

The first thing is to describe the feelings that patients have about being assessed and managed comprehensively. They really like it when you take the time and effort to ask them questions about these different clinical domains to actually touch them and examine their skin, examine their joints, examine their enthesis, examine their spine. They feel more taken care of, and that builds trust between the clinician and the patient, and it makes for a more satisfying relationship on both sides. And so I think that that's a key thing.

The other is that our goal is to try to treat patients to a target of low disease activity or remission. And according to the GRAPPA guidelines for getting to such a state, we want to address adequately each of these clinical domains. We can't just leave a few of them out in the field. So what, as long as we're treating the arthritis, that's all we care about, we've really got to take care of the whole picture.

Rebecca Mashaw:

You just mentioned that there are some clinical trials being conducted on combination therapy. Is that correct?

Dr. Mease:

That's correct.

Rebecca Mashaw:

Are you participating in those trials? Is there anything you could tell us about those?

Dr. Mease:

Yes. There's a very interesting trial known as the AFFINITY trial being conducted by Janssen in which they're testing a combination of a TNF inhibitor, golimumab, along with an interleukin-23 inhibitor, guselkumab, and then comparing that combination with monotherapy in patients with psoriatic arthritis. So we're very interested in seeing whether that yields better efficacy and then importantly, what the safety profile of that combination will be.

Rebecca Mashaw:

When do you foresee having some results from that study?

Dr. Mease:

I expect that we'll see some results say in a year's time. But I should mention that they've already piloted this approach in the disease, ulcerative colitis, in a trial known as the VEGA trial, in which they also studied this same combination and found that there was a greater efficacy with the combination arm, which was not overly surprising. The safety was just as good in that combination arm as in the monotherapy arms. And they did a novel thing of doing colon biopsies looking at proinflammatory and anti-inflammatory gene expression, and found that there was a synergistic effect, a much, much greater effect on reducing the bad guy genes and improving the good guy genes with the combination within either monotherapy. And I think that this kind of grounds, our clinical observation in translational science observations, which I think is a much firmer foundation for promoting this combination therapy approach.

Rebecca Mashaw:

It's very interesting. Do you have any last thoughts that you would like to share with your colleagues about diagnosing and treating patients with PSA?

Dr. Mease:

Enjoy taking care of this complex and interesting disease. It is challenging, but this is what we become rheumatologists for.

Rebecca Mashaw:

Thank you very much for taking the time to talk with us. This has been very interesting, and we hope to speak with you again soon.

Dr. Mease:

Thank you, Rebecca.