 Just highlighting on therapeutics for psoriatic arthritis: we now have these new head-to-head clinical trials, where instead of having a specific drug for psoriatic arthritis compared to placebo, we now actually have drug against drug in psoriatic arthritis. This is really new for us.

We're hoping that this will bring a lot of new information to help the clinicians with treatments. Just like in rheumatoid arthritis, we have oral disease-modifying agents—methotrexate being our anchor, our most comfortable, sort of go to medication. However, many patients don't respond completely on methotrexate, and then we need to look at the biologics and the synthetic compounds that are used in psoriatic arthritis. Anti-TNF therapy, for example, is one of our tried and true. It has been really good for the skin and the joints. And then we can go on to the IL-17 inhibitor class; we also have the JAK inhibitors, we also have PDE-4 inhibitors. And then we have some much newer ones that are approved in psoriasis, not psoriatic arthritis quite yet, such as the IL-23 inhibitors. So, we're really expanding our toolbox for this disease. And I think it's important to note that now with these head-to-head trials...they do have some mixed results. So it's not so clear cut.

I think we do have to personalize our care, and really input our clinical judgment into these patients, because not everybody is like a clinical trial patient. So, we really need to look at them in terms of what other comorbidities they might have, what have they tried, Is this a TNF-naive population, is this a methotrexate-naive population. There's lots of questions about how a patient presents and the treatments that we should be offering them.

Recent Achievements in Psoriatic Arthritis Management

Fitting Biologics into the Psoriatic Arthritis Spectrum

 I think the management, and what therapy to choose, is really a big question now, especially because we have so many to choose from. I think one of the things that strikes me the most of what's going on is that as we're getting more and more treatment, the skin psoriasis is actually getting cleared. And it's getting cleared for a long period of time—sometimes up to 52 weeks. Unfortunately, when you look at the joint side, we don't have as great of a response, so we're really not hitting 100% clearance of all the joints. And that leaves a lot of room for clinical judgment and for treatment options. So, despite having all the successes in skin psoriasis, we're not seeing the same success in joint manifestations. We really need to look at other options. There are many that are still on the horizon that are in early phase 1 and 2 trials. But for the ones that are FDA-approved already, I'm really grateful that we have more than 2-3 to go to. So we do look for what we call domain strategies. This is following the graph of treatment domains, for example, where they look at whatever your prominent domain is for psoriatic arthritis. Is it the skin that's driving the discomfort? Is it the joints that are driving it? Is it the axial skeleton? Is it the enthesitis? Depending on the domain, we actually become a little bit more specific about the types of treatment that we use.

For instance, I would say that the IL-17s and the up-and-coming IL-23s probably have a stronger and more robust response for the skin. So, if somebody is having more skin than joint discomfort, then we could see how reaching out to one of those agents makes sense. If the joints are much more problematic than skin, then you could see where a TNF inhibitor, for example, might be good in combination with methotrexate, which is one of our anchor drugs. Whether or not we do combination or monotherapy, those are all choices that we can make with shared, informed decision making with our patients.

Achieving Individualized Psoriatic Arthritis Care

 I think your question about emerging therapies is really important right now, because we have so many to choose from, and this was not always the case. For patients with psoriatic arthritis, we've always had to borrow from rheumatoid arthritis. Basically, they would be studied in rheumatoid arthritis first, and then we would borrow what we've learned into psoriatic arthritis. And that has really been different now. At ACR 2020, we're really looking at all the different psoriatic arthritis treatments that have been designed and tested for psoriatic arthritis patients only, and that's really exciting.

That's because we understand more about the psoriatic arthritis disease processes now. We understand more about the pathophysiology of disease. We are also much, much more engaged in the different manifestations. It has a wide spectrum of clinical manifestations—not only the skin and the joints that are affected, but also the enthesitis, which is where the tendon meets the bone, and dactylitis, the swelling of the whole digit. In addition, there's also all these comorbidities that we're learning that are associated and related to psoriatic arthritis specifically, where we're trying to get more personalized in our treatment.

Most Promising Psoriatic Arthritis

 There's a couple of great scientific forums that are ongoing. Like any ACR meeting, or there's always so many competing events, because there's so many new drugs and different things that you want to do and see. But there is a PSA treatment kind of focus and I'm moderating and we have three sessions in that that I would love to highlight. We are looking more at patient reported outcomes, which is awesome. We're having the patient's viewpoint be part of the decision making. So, we have a talk on that we have a talk on co management, which is what I just talked about with a dermatologist. So that's really exciting.

Then we also have the newest data, the head-to-head trials that we're really trying to wrap our heads around their interpretation. How do we use these with all the traditional, phase 3 clinical, placebo-controlled trials as well? All of this is good data. I think the question is, 'How does it pertain to my patient that I'm seeing in my office in front of me next week?' I think the more information we get, and the more we're able to have these dialogues during these ACR meetings, is really going to give us the tools to feel confident with.

Highlighted Psoriatic Arthritis Sessions at ACR 2020

This was a conversation with Dr. Sergio Schwartzman from New York. We talked about how the complexity of the presenting symptoms in an individual patient can be so daunting even on the initial evaluation, because you can have, as I just previously mentioned, the 6 domains of involvement, and most patients have between 2-4 domains at one time. So, there's a complexity from the musculoskeletal and skin perspective. You can have different types of psoriasis, you can have different types of arthritis, and you can have combinations of these forms of joint inflammation: enthesitis, distal interphalangeal joint involvement, axial skeleton, other peripheral joints. You take that complexity, and then you add to it the comorbidities—diabetes, obesity, hypertension, metabolic syndrome, anxiety, depression—and it really makes for a very complex decision-making and evaluation process.

So, we talked about how this can be carried out in the office and in a reasonably efficient manner, and how important it is for us to be able to, on the initial evaluation, know exactly what a patient is dealing with from these different perspectives, so that you can have a conversation with them, share decision making, and come up with a treatment regimen that is safe and effective.

How Different Psoriatic Arthritis Manifestations Affect Care

 Well, there are many centers around the country—ours is one, there's New York, Philadelphia, Boston—where we see patients with dermatologists. So, the patient was psoriatic disease is evaluated by a dermatologist, rheumatologist, often trainees, rheumatology fellows, and dermatology residents. We find that this is a very effective strategy to be able to discuss the various elements of the patient's presentation with dermatology present to provide perspectives.

But it goes beyond that rheumatology-dermatology dyad. There's also other elements that relate to the comorbidities I just mentioned, and that includes gastroenterology, cardiovascular disease, endocrinology, and, of course, the general practitioner. This is a team that really is virtual and real. So, the "real team," in terms of being in the office include dermatology and rheumatology, but they're reaching out to these other caregivers to address specific problems that these patients are addressing. We also use psychiatry a lot, and nutrition for weight loss and optimizing dietary regimens. So, there's a lot of support that's required for some patients in order for them to manage the journey with this disease.

The Modern Psoriatic Care Team

 Dr. [Elaine] Husni from the Cleveland Clinic and I had a long discussion about this, as well as Linda Grinnell-Merrick from the NP perspective. What we've learned is that there's a lot of efforts around the world actually to develop outcome measures, to help us understand how patients are doing. And we have many of them. We have MDA, VLDA, as well as DAPSA and others. What we've learned is that those are very valuable in helping the doctor understand whether a patient is reaching a certain bar. What we do know, though, is that patients view their illness and how they're doing completely differently. And there have been a number of studies not only in psoriatic arthritis, but an axial spondylitis and rheumatoid arthritis where you see a physician's understanding of where the patient is. And it's really very different than what the patient is thinking. We don't understand all this right now, but probably a lot of it has to do with how a patient is doing in their life—how are they managing their activities? How are they able to enjoy their families and be able to perform well at work? We need better ways of capturing that.

And one of the instruments that's now being used in many centers is called PROMIS. This is a questionnaire that is given to the patient before they see their doctor. It's electronic. It's really guided toward how the patient answers a question, as to what next question comes up. And it provides a doctor a snapshot, before they even see the patient, of how the patient is doing in terms of fatigue, pain, wellness, and their activities. I think incorporating that into our evaluations, which we've worked very hard to complete, will provide a more comprehensive picture of how patients are doing.

The Psoriatic Patient's Role in Improving Care

 I think we're going to see data on new agents that are in phase 3 trials right now. Of course, one of them is bimekizumab, which is an IL-17 ANF antagonist. Upadacitinib, a JAK-1 antagonist, will have more available data moving forward and will probably come out into the market by—bimekizumab, as well. We're going to have more data on agents that block interleukin-23, which are currently in phase 2 and 3 trials. And I think that we may even have, with the application of newer technologies to understand what's going on in the skin and in the joint, more information on basic mechanisms that are driving these diseases. I think is really going to be extremely important.

I think this is going to be an exciting time in the field of psoriatic disease. So, psoriasis has really moved along in a very swift manner, such that we have outcomes in psoriasis, which are truly unimaginable, as recently as 5 years ago. We're not there yet in psoriatic arthritis, but I think we're gaining the knowledge and the strategies to put us in a good footing to see that happen over the next 5-7 years.

What Should Highlight ACR 2021

 Non-radiographic axial spondyloarthritis is a relatively new term. It was first coined as part of the classification criteria for spondyloarthritis in 2009. And that completely reorganized the way that we look at spinal arthritis. So, the first division is separating it out into peripheral spondyloarthritis and axial spondyloarthritis. And since we're only traveling down the side of the axial spondyloarthritis component, non-radiographic axial spondyloarthritis refers to a phenotype of patients who have axial spondyloarthritis, but who have not had any changes on X-rays.

And those patients can be categorized via 1 of 2 pathways: patients who have MRI changes, have had back pain for greater than 3 months and the onset of pain before the age of 45, or patients who are HLA-B27 positive, with the same back pain categorization in terms of the classification criteria, but with more features of spinal arthritis in general.

I think the challenges about non-radiographic axial spondyloarthritis are the first is that it is not a diagnosis. It's a classification criteria. A diagnosis is made at the discretion of the physician who's evaluating the patient.

So, the term itself is not meant as necessarily a diagnostic, but more to categorize patients in a uniform manner, so that they can be included in clinical trials. But this concept, though, has evolved to helping rheumatologists identify patients with this group of diseases much earlier than what we had done before. So the first challenge, then, is in understanding what non-radiographic axial spondyloarthritis is. And the way to think about this is that it is part of the entire spectrum of axial spondyloarthritis. It has very similar presentation manifestations, and co-manifestations and comorbidities. It differs in that it may identify patients much earlier than what we see in patients with radiographic disease. And one needs to understand that the disease burden for non-radiographic axial spondyloarthritis is the same as it is for radiographic axial spondyloarthritis or ankylosing spondylitis.

I think rheumatologists need to be educated—and that's the challenging perspective, as to the fact that this entity exists that is characterized by very similar symptoms and what we see ankylosing spondylitis, but it probably represents an earlier part of the disease process, in terms of how it evolves over time.

I think the first challenge is to recognize that these are classification and not diagnostic criteria. The second challenge is to understand that this falls within the spectrum of really one disease process. And I think the third challenge is to think of this as such, but in a manner that necessitates taking a very aggressive approach to treatment, because the disease burden is equal to what we see in ankylosing spondylitis or radiographic axial spondyloarthritis.

There are some subtle differences. Non-radiographic disease is equally present in men and women, whereas ankylosing spondylitis is more common—2:1—in men than it is in women. And the disease may present a little bit differently, more like a fibromyalgia pattern or cervical disease, and not necessarily a lower back pain. So I think that the subtle differences are also important differentiations.

Current Issues in nr-axSpA Diagnostics

The RAPID-axSpA study was a study that actually included both patients with non-radiographic axSpA and radiographic axSpA. Two major points that I think are unique about that study are, number one, this was the first time that this concept of non-radiographic axSpA was tested in an attempt to get certolizumab approved by the FDA. And, number two, that the Advisory Committee to the FDA voted in favor of having it approved.

And I think, number three, is the point that you just mentioned, which was that in a four-year span, we had only 2 patients of 44 patients that entered this study convert from non-radiographic axial spinal arthritis to radiographic axial spondyloarthritis. So, I think it was a pivotal study. I think that it introduced the concept to the rheumatology community. And now that we have long-term data for a specific therapy where data is collected and objectively analyzed, we see that the numbers of conversion or progression of the disease, as measured by X-ray changes, is very much mitigated by treating the disease early and aggressively.

Takeaways from Four-Year RAPID-axSpA Data

 The C-axSpAnd study was also a pivotal study. This study resulted in the first therapy that actually was approved for non-radiographic axial spondyloarthritis. And the lessons that were learned from the previous studies were that you needed a longer term, in terms of determining efficacy. So, the primary outcome was at 1 year. You needed a uniform population of patients, so these were all patients who fulfill the categorization of non-radiographic axial spondyloarthritis from the classification criteria. And probably the most challenging component of this was that there was a liberal component in terms of patients escaping at an early point of the study.

So, I think with that as background, what we then saw was that in the primary outcome, not only was there a statistically significant, large delta difference between the treatment arm and the placebo arm, but number two—and I think importantly for me—was that the placebo arm response was very low. And I think that tells you that this was a well-constructed and well-populated study, with patients that fulfilled appropriate classification criteria, and importantly, had a dramatic response to the therapy certolizumab that was being tested.

Advancing Long-Term Arthritis Care at ACR 2020