Melanie Cole (Host): Welcome. Today, we're taking a closer look at psoriatic arthritis, and my guest is Dr. Eric Ruderman. He's an Associate Chief and Professor of Rheumatology at North Western Medicine. Dr. Ruderman, tell us a little bit about psoriatic arthritis. Is it a new condition? Is it just more widely recognized now? What is the prevalence of it?

Dr. Eric Ruderman (Guest): It's not a new condition. It's a disease that's been recognized for perhaps somewhere between 40 and 50 years as something that's separate from rheumatoid arthritis. I think something that's being recognized now is that it's a fairly frequent occurrence in patients with psoriasis, and as more and more psoriasis patients are being recognized by primary care physicians and dermatologists — particularly now that we have better treatments for psoriasis — we're recognizing the 25 or 30% of those patients who also have concomitant psoriatic arthritis.

The National Psoriasis Foundation ran some numbers several years ago. There is an estimated — about a million patients with psoriatic arthritis in the United States. It's not clear that that's a completely accurate number, but that's a reasonable ballpark.

Host: Wow. Are there some separate clinical phenotypes of psoriatic arthritis?

Dr. Ruderman: Well, traditionally, we've thought about psoriatic arthritis in different types in terms of which joints are involved — whether it's a few joints, a lot of joints, just the DIP joints, the distal joints of the fingers, whether there's axial involvement. That was always the historical way. There are certain criteria that go back about 40 years called the Moll and Wright Criteria that look at that. As it turns out, it's not 100% clear that those really matter that much — that patients with different phenotypes of psoriatic arthritis respond similarly to different medications. The only exception being maybe spine involvement or axial disease which responds less well to more traditional agents and better to biologic agents — some of the newer drugs we're using.

I think the other thing that has changed more in the last 10 years or so is that we're recognizing that psoriatic arthritis is not really an independent entity — we don't have psoriasis, and then we have psoriatic arthritis. It's a spectrum. People have psoriatic disease, which may include skin involvement. It may include nail involvement. It may include joint involvement. It may include entheseal involvement of tendons and ligaments, dactylitis, or sausage digits, and also ancillary diseases like uveitis, or inflammatory bowel disease, which is often associated with psoriatic arthritis and psoriasis. I think the big change in looking at this diagnosis in the last 10 years or so has really been to address it as a spectrum of disease that we call psoriatic disease and not more specifically psoriasis or psoriatic arthritis.

Host: Along this spectrum, might these occur individually or in combination, and do they typically evolve over time into a different type on the spectrum?

Dr. Ruderman: They absolutely can occur individually and in combination. There are patients who just have a skin disease and never get joint involvement. There are patients that have a mild skin disease and very severe joint involvement. There are patients that I've seen who have only nail involvement. Yes, they can occur individually. They can change over time. Patients who have never had GI involvement may 10, 15, 20 years into their disease develop some diarrhea and turn out to have inflammatory bowel disease, which isn't really part of the psoriatic spectrum but can be associated. Things do change over time, and that's one of the challenges of managing these patients is to be aware as you follow them of other manifestations of the disease that they may not have had when they first presented.

Host: Then speak about clinical presentation, and what are some of the hallmarks that would either signal a primary care provider to send a referral over to a rheumatologist or even a dermatologist who would spot this. What are the main signs?

Dr. Ruderman: That's a great question, and it's one of the things we've really been focusing on. The main signs are do you have a patient with psoriasis and now symptoms that suggest inflammatory arthritis? What do I mean by that? I mean patients who have persistent, swollen joints, patients who have prolonged morning stiffness — morning stiffness for 45 minutes, or an hour, or more is a hallmark of inflammatory arthritis rather than osteoarthritis or degenerative arthritis. Patients who have recurrent tendinitis, enthesitis, tennis elbow, Achille's tendinitis, plantar fasciitis in the setting of psoriasis are all things that might prompt an evaluation by a rheumatologist.

For dermatologists, one of the things they've learned to look for is nail involvement. Psoriasis patients can get nail changes, and it turns out the presence of those nail changes are actually very well correlated with the likelihood with developing psoriatic arthritis. A patient who has psoriasis and has had persistent nail changes who suddenly has some joint symptoms we need to think twice about whether we think they have psoriatic arthritis.

Host: How important is the early diagnosis as being crucial to improve outcome prediction and to prevent long-term structural damage and disability?

Dr. Ruderman: It is very important. Like many of the other types of inflammatory arthritis that we manage, this disease is not just about symptoms, but also about the long-term impact on structure, on joints, and function because structure really drives long-term functional changes. Not all patients with psoriatic arthritis are going to get destructive arthritis and structural changes over time, but many will — perhaps as many as half of them. It is important to identify the disease early and identify those patients early who is going to go on to have those changes so that we can institute therapy to prevent damage.

One of the challenges we still struggle with is identifying who are the patients who are going to have structural damage over time if not adequately treated. But certainly, the severity of disease, number of joints involved, and absolutely, the presence of structural damage on an X-ray when first evaluated are all predictive of more damage over time if not adequately treated.

Host: As far as diagnostic criteria, are there some valuable prognostic tools that you use to aid in early diagnosis and to see how many joints — or really what's involved?

Dr. Ruderman: Well, unfortunately, we don't have the best prognostic criteria. We can certainly make the diagnosis early on, and it's a clinical diagnosis. It's the presence of arthritis that has an inflammatory pattern of symptoms, the joints that are involved — hands, the distal joints of the hands — the presence of enthesitis or tendinitis, which is a real hallmark of psoriatic arthritis. All of those can help make an early diagnosis, and obviously, the presence of psoriasis. It's interesting to note that typically, arthritis that we see that's associated with psoriasis develops about 10 years, on average, after the skin disease develops. That gives us our early marker of somebody at risk for skin disease. What we don't know is how to identify the patient who's going to have the joint disease in the next year or may never — and that's an area of active research, to try to understand that transition better.

Host: As we talk about the standard of care and treatment, I'm going to throw a couple of questions at you here at once. Why do the medications — that usually works quite well for rheumatoid arthritis — they don't work quite so well for psoriatic arthritis. Speak about the standard of care and the therapies you might try, and why it's so different from rheumatoid.

Dr. Ruderman: Interestingly, some do, and some don't. It is not completely different from rheumatoid arthritis. To start with, simple, symptomatic management, non-steroidal anti-inflammatories that are an important piece of our symptomatic management of rheumatoid arthritis patients we use in psoriatic arthritis. They can work there as well. The key though is that those drugs don't change the course of the disease, they're just simply treating symptoms.

In rheumatoid arthritis, we can often make people better very quickly with low doses of steroids, particularly prednisone. It doesn't tend to work as well in psoriatic arthritis, and I don't know that we really understand why that is, but it's a very clear issue.

And then, you get to the disease-modifying drugs, the more aggressive therapies. The standard of care in rheumatoid arthritis as a first-line drug has been methotrexate. That's a drug that works in psoriatic arthritis, and so we often do use that. Interestingly, methotrexate has never been officially indicated by the FDA for treatment of psoriatic arthritis, only for psoriasis, but we use it. It does have some benefit. In fact, a recent study demonstrated that quite clearly. I think over the years we haven't had as much data, and we've had more anecdotal experience that says methotrexate works, but methotrexate works.

If methotrexate doesn't work, then we get into second-line agents like biologics. Some of the biologics that work in rheumatoid arthritis work in psoriatic arthritis and some don't. I think the difference there has to do with the nature of the pathophysiology of the disease. Despite the fact that both are inflammatory types of arthritis, there are different cell types involved; there are different inflammatory signals involved. TNF Inhibitors, Tumor Necrosis Factor Inhibitors, which have really changed the landscape of treatment in rheumatoid arthritis, work well in psoriatic arthritis. We've been using them in psoriatic arthritis since shortly after we started using them in rheumatoid arthritis 20 years ago. They work well. They also treat skin disease. That's often become first-line therapy.

On the other hand, Interleukin-6 Inhibitors, which are very effective in rheumatoid arthritis — or Abatacept, which is a T-cell Modulator — don't work nearly as well in psoriatic arthritis. IL-6 inhibitors really don't work at all. Abatacept works. It's been approved for treating psoriatic arthritis but is less effective than some of the other drugs that we use.

On the flip side, there are newer agents that we use to treat psoriatic arthritis that we've actually followed on from the dermatologists. The dermatologists have really moved the field forward in terms of treating skin disease largely because they can biopsy the skin and really understand what's driving the skin disease. After TNF Inhibitors the next, big leap forward were drugs that targeted the IL-17/IL-23 pathway — there's an IL-12/23 inhibitor named Ustekinumab, and a couple of IL-17 inhibitors that actually turn out to work well in psoriatic arthritis. Interestingly, they work very well in skin disease, better than the TNF Inhibitors.

And then finally, the newest generation of therapies that we're beginning to look at are drugs that specifically target IL-23 alone. The first of these is a drug called Guselkumab that's been approved to treat psoriatic skin disease. It's in late-stage development for psoriatic arthritis and looks to be effective.

Interestingly, with all of these each new iteration — each new step forward in therapies for skin with better and better results to the point at which these IL-23 inhibitors can completely clear the skin in 50% or more of patients. They haven't resulted in similar improvements in the number of patients with the joint disease who respond, so that remains a challenge to find the right drug for the right patient. That becomes the clinical target is to look at the spectrum of disease and identify the right drug that's going to address all of the manifestations in that particular patient.

Host: Tell us what you and your colleagues at Northwestern Medicine are doing to advance the understanding and treatment of psoriatic arthritis?

Dr. Ruderman: I think one of the things we're doing is we're working very closely with our dermatology colleagues. We have a standing clinic that treats patients with psoriasis skin disease and joint disease. We work together, so rather than trying to communicate after the visits we actually see them in combination at the visit and work with a dermatologist, a rheumatologist — usually myself — and the patient to identify the best therapy that will address all of the different aspects of the disease. Is their skin disease more prominent? Is their joint disease more prominent? Has the treatment that we've started them on tackled their skin disease, but their joints have worsened? Do we need to make a change? Do we need to add something? Do we need to try something different?

I think that's an area that we're working on. That's an area that I think people are working on broadly across the country and across the world is to try to really figure out how we can coordinate therapy better for these patients to make sure that we use the optimal therapy in the right patient to address their individual disease parameters.

We're not yet in a place to do that genetically. We're not yet in a place where we can personalize things by looking at what's happening at the gene level, but we can do so clinically. I think the next step is to really look at more specific biologic prognostic markers that help us choose the right drug. We're still in a bit of a trial and error era if you will. We know drugs that might work. We'll select something, try it, and if it doesn't work, we'll try something else in the next step. We're beginning to explore this now and beginning to look at biopsies, look at biologic specimens to try and understand what makes this disease tick. The next step would be to be able to select the right drug that we know is highly likely to work in a patient and not simply try something and see what happens.

Host: Then wrap up for us, Dr. Ruderman, what else would you like providers to know, and when do you feel it's important that they refer?

Dr. Ruderman: I think I want people to know that this is an important disease, and I think honestly, at the first hint or sign that a patient may have psoriatic arthritis, that's the time to refer. It's a psoriasis patient. I think it's important for providers to know — particularly primary care providers — that the severity of the skin disease doesn't really impact the likelihood of having the joint disease or the severity of the joint disease. Many primary care physicians are managing patients with fairly mild psoriasis who may have a little scalp psoriasis or a little psoriasis on their elbows, and they're managing them with topical steroids. That's completely appropriate, and those patients may not even follow regularly with a dermatologist to treat their psoriasis, but I think it's important to recognize that any psoriasis is a potential signal that the patient may have psoriatic arthritis.

If you have a patient with psoriasis who develops joint symptoms, particularly swollen joints, particularly inflammatory symptoms — stiffness in the morning — particularly at a younger age when you wouldn't otherwise assume that they're going to have osteoarthritis and they're 65, or 70, or 75, those are patients we would like to see in rheumatology because in many cases we can help them quite a bit.

Host: Thank you so much, Dr. Ruderman. What an interesting topic, and thank you so much for coming on and explaining it to other providers, and the medications, and the biologics that you try, and the standard of care. This is Better Edge, a Northwestern Medicine Podcast for physicians. For more information on the latest advances in medicine, please visit NM.org, that's NM.org. This is Melanie Cole. Thanks so much for tuning in.