Laura Coates, MBChB, on Updates to GRAPPA Guidelines on PsA

In this podcast, Dr Laura Coates discusses the changes made to the guidelines for treatment of psoriatic arthritis by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Laura Coates, MBChB, MRCP, PhD, is an associate professor and Senior Clinical Research Fellow at the University of Oxford in Oxford, United Kingdom.

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TRANSCRIPT:

Speaker 1:
Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw, and I'm very pleased to be here today with Dr. Laura Coates, who is with the Department of Orthopedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford in the United Kingdom. She's also the lead author of new updated recommendations from The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, better known as GRAPPA, on the treatment of psoriatic arthritis. So thank you very much for joining us today to talk about these guidelines.

Dr. Laura Coates:
Thank you for having me.

Speaker 1:
So to begin with, what motivated GRAPPA to update its treatment recommendations for PSA?

Dr. Laura Coates:
So the development of treatment recommendations within GRAPPA has always been one of our core aims. It's in our mission statement to provide support for clinicians across the world who are treating people with psoriasis and psoriatic arthritis. And our last recommendations were published in 2015. These recommendations were meant to be in 2020, but world events somewhat overtook us and delayed things a little, which is why they've just come out now. But the aim really was to update the recommendations from 2015 because obviously this is a rapidly evolving field. Things change regularly. We have new evidence on old drugs and then we have evidence on new drugs as well. And to be useful and to be relevant in the clinic, these recommendations need to be as up-to-date as possible. So our aim was just to look at the literature from when we'd done the last search, prior to the 2015 recommendations, and provide a further update and put that in context

Speaker 1:
Because GRAPPA uses a domain based approach to the treatment of psoriatic arthritis or psoriatic diseases in general, could you give us a brief overview of what those domains are?

Dr. Laura Coates:
Yeah. So within psoriatic disease, GRAPPA considers six key domains. So peripheral arthritis, enthesitis, dactylitis, axial disease, skin disease, and nail disease. So we've got four kind of musculoskeletal components, which is usually led in treatment by rheumatology and then to dermatology, manifestations in the form of skin and nails.

Speaker 1:
The publication mentions that in this particular update you chose to add a new domain by dividing what had been one called comorbidities into comorbidities and related conditions. Can you explain the rationale behind that and what are these related conditions?

Dr. Laura Coates:
So psoriatic arthritis is associated with a lot of different comorbidities, and we see that in all of our patients, but there are some of these related conditions which are actually part of the spondyloarthritis spectrum. They're not a true comorbidity like depression or cardiovascular disease. These conditions are more directly related in terms of pathogenesis. So really that includes inflammatory bowel disease and uveitis. And obviously, they're part of that spondyloarthritis spectrum, part of the same underlying family. And it's quite different the way we consider treatment for those two groups. So related conditions have clear studies looking at efficacy or sometimes risk with some of the drugs that we use in PSA, whereas comorbidities, the treatment is typically led a little bit more distantly from the rheumatologist or the dermatologist, and the medications don't have quite the same overlap in terms of treating the related conditions.

Speaker 1:
So that pretty much answers my next question, was how does this division into these two categories help clinicians in choosing therapies for their patients? Could you give us a little bit more information on that part of the update?

Dr. Laura Coates:
Yeah, so we wanted to include the related conditions data in the main figure. So alongside those six key domains like arthritis and skin disease, we also have the efficacy for drugs that we commonly use in IBD and uveitis, because that's going to be one of our big decision points. If I'm planning a treatment for somebody who has active psoriatic arthritis, then whether or not they have IBD or uveitis is really going to be pushing me towards or away from certain drugs that may directly benefit that related condition, and hopefully a bit like treating the skin disease and the joint disease with a drug that will benefit both, we can treat the psoriatic disease and their IBD, for example, with a drug that's licensed and available to treat both conditions. So they were considered as part really of the main focus of the recommendations. And then the comorbidities data is a little bit more removed. It's not in that main figure. It's also a lot less evidence-based. There's not as such strong evidence around the other comorbidities.

Speaker 1:
The update acknowledges that most patients with psoriatic arthritis present with this multi-domain disease, and treatment decisions need to reflect that reality. And this is quoting from the guideline, "Therefore the recommendations for each domain were combined in a single treatment schema to guide therapeutic decisions." Could you walk us through that schema? Can you explain a little bit about how it works?

Dr. Laura Coates:
Yeah, absolutely. So it's somewhat similar to the figure that we had back in 2015, so if listeners are familiar with that, that will help. And the idea is that we summarize all of the evidence for the individual domains, so the six key domains of psoriatic disease, and then the drugs that are also efficacious in IBD and uveitis. So there's a little flow chart for each of those different domains. But what's key is right at the top of the flow chart, we're asking clinicians to firstly consider which domains are involved in that particular patient, whether there's any patient preference, obviously what treatments the patient has had before or whatever concomitant therapies they're taking. And we're aiming then to guide people to choose a therapy that can address as many domains as possible.

So for example, if someone has enthesitis and axial disease, you can look at those two flow charts and see which drugs work for both, and then that might be a good treatment for that particular patient. Similarly, if someone has arthritis and IBD, you can look across those different flow charts, choose a drug that makes sense for that individual and then move forward. And then at the bottom of the flow chart, when we bring that treatment decision back to that individual, we've also mentioned obviously the comorbidities that may impact on a choice of therapy as well, or potentially guide monitoring. So it may not change your treatment, but you might want to monitor a particular side effect or issue a little bit more closely.

And then obviously, as with any treatment recommendation, we're asking people to treat with the drug that they think will help the most domains as possible and then reevaluate periodically and modify that therapy as required. So if somebody doesn't respond to treatment or if they respond but then subsequently lose response, you would just go back around the circle again, think about then which domains are involved, which drugs the patient has tried before, and then pick a new therapy for that patient.

Speaker 1:
Is it accurate to call this a treat to target approach?

Dr. Laura Coates:
So I think the figure itself doesn't really talk about treat to target, that's very much around selection of drugs. But we have overarching principles that are part of the recommendations, and they mention the idea of goals of treatment, that that should be decided between the clinician and the patient, and that ideally we should be aiming to minimize the disease, but also to minimize any side effects from therapy at the same time.

Speaker 1:
So what are the targets in PSA? I've seen low disease activity, true remission. Are these the key points that you're aiming for when you're treating a patient with psoriatic arthritis?

Dr. Laura Coates:
I think conceptually we should all be aiming for remission. We want to get our patients back to normal, back to normal life, totally unrestricted in terms of their disease. And so that's always our main aim. The problem is that unfortunately we do have to be realistic, and in some patients that's just not possible, particularly those who've had disease for a long time, maybe have existing joint damage and other comorbidities, or who have limited access to treatment for different reasons. So we often talk about aiming for a more realistic target of remission or low disease activity, which is also sometimes termed as minimal disease activity. And there are a number of different ways of assessing that in psoriatic arthritis. To some extent that has to be individualized to the different patients. But we use criteria for minimal disease activity, which take into account the different domains. So we really believe in GRAPPA that we should be thinking not just about the joints, but about other aspects of the disease. And minimal disease activity looks for disease control in the peripheral joints, in enthesitis, in patient reported outcomes, and in the skin disease. So it's a more global assessment of disease activity in any individual patient.

Speaker 1:
So this is based primarily on clinical signs and symptoms. Are there biomarkers or other indicators that are used to help gauge whether a patient is approaching that minimal disease activity goal?

Dr. Laura Coates:
Yeah, unfortunately that's still a big gap for us. So in clinical practice, we do routinely check a CRP, C-reactive protein, and if that's high, that can be associated with high disease activity, but obviously it's not specific. It can be caused by other diseases, so we can get false high readings. And we know that about 50% of our patients with psoriatic arthritis never get a high CRP. They can have very active disease, but that just doesn't show in the C-reactive protein. So I think that's a big unmet need for us moving forward is having more accurate biomarkers that we could use to monitor patients.

Speaker 1:
Were there any other major changes to the 2015 recommendations included in this update?

Dr. Laura Coates:
I think the main changes were inclusion of new medications. So data around IL-23 inhibitors, around JAK inhibitors, and inclusion of them in these multiple domains. We had a little bit of changes from some new data on old drugs, so a little bit of better evidence around methotrexate in different domains of disease and around more intensive therapy.

Speaker 1:
Were there any changes in terms of drugs that are no longer being recommended for use in psoriatic disease?

Dr. Laura Coates:
I think the big change has come, and again, it's at a domain specific level, in the IL-23 inhibitors. So they've appeared on the scene obviously as effective drugs for peripheral arthritis, enthesitis, dactylitis, really good drugs for skin disease, but have had negative trials in ankylosing spondylitis and a newer negative trial for the IL-12/23 inhibitor, ustekinumab, as well. So that was provisionally recommended for axial disease in 2015 based on a very small open label study. But subsequent large RCTs have been negative. So at the current time we don't feel these should be used for patients with significant axial disease, but obviously they are still licensed for peripheral psoriatic arthritis and psoriasis.

Speaker 1:
So what do you foresee in the near future in terms of PSA treatment options? Do you think this pace of advance is going to continue for a while?

Dr. Laura Coates:
I think it's been a fascinating time and things have changed so much in the last decade in terms of the availability of therapies, which is absolutely brilliant for our patients. I'm hoping we'll see a lot more evidence in the axial domain. So we now have three groups of drugs that have shown efficacy in [inaudible 00:13:01] trials, but there's a lot more work being done specifically in axial PSA, how to classify it, how to measure it, how to study it, and that will hopefully help us to develop new therapies.
I think there's a lot of interesting combination therapies, particularly for patients who have very resistant disease. That's something that hasn't been studied to a huge amount, but is starting to gain some traction because we do have patients with particularly resistant disease who failed multiple drugs, and they're very difficult patients to deal with in clinic. We just don't really know what to do.

And obviously the more drugs we have, the more we need studies about strategy. How do we choose a drug? How do we match a drug to a different individual? What order do we try the drugs in? All of those questions come to the fore because we now have so many options. And that's really where we are particularly lacking evidence. We've got a lot of studies to show that a drug works compared to placebo or maybe compared to one other drug. But very few studies looking at treatment escalation, a combination, rapid escalation, tapering, all of these questions that come to us every day in our clinics when we see individuals.

Speaker 1:
Well, thank you very much for spending some time with us to talk about this. It's very interesting and we'll look forward to speaking with you again soon.

Dr. Laura Coates:
Thank you very much.

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