 titled, “Biologics and Advanced Therapies in the Management of Psoriatic Arthritis.” I’m Dr Anthony Turkiewicz of Rheumatology Associates here in Birmingham, Alabama. Joining me today in this discussion are my colleagues: Dr Steven Feldman of Wake Forest School of Medicine in Winston-Salem, North Carolina; Dr Hillary Norton of Santa Fe Rheumatology in Santa Fe, New Mexico; and Dr John Tesser of Arizona Arthritis & Rheumatology Associates in Phoenix, Arizona.

We’ll start this discussion today with you, John. If you don’t mind, give a high-level overview of the pathophysiology of psoriatic arthritis [PsA]. Please bring up the unique role that perhaps genetics, environmental factors play in this disease.

: Similar to all of our systemic autoimmune diseases, we identify genetic susceptibility and then environmental hits that lead to the clinical development of these diseases. With psoriatic arthritis there have been more than 11 gene types that have been identified, and that’s as of 2011, that confer genetic susceptibility. And although we all look to 

 as being the most prominent one, it in fact is only one of many.

 is not associated with spondylitis and sacroiliitis and PsA, as of course it is in ankylosing spondylitis. Having said that, the genetic susceptibility and environmental factors need to be put into the context of site matters. With PsA, as we all understand it being a systemic disease not just arthritis, we can look to joint, synovium, but also skin and gut, and also the enthesis, which is the most prominent musculoskeletal site that grabs our attention.

The environmental hit of biomechanical stress on the enthesis leads to an outpouring of interleukin-23 [IL-23}. It’s the interleukin-23/17 access that drives this disease. Now with psoriatic arthritis as opposed to rheumatoid arthritis, we’re not looking at T- and B-cell interaction so much, which helps to understand why there are no autoantibodies that we’ve identified in the pathophysiology of the disease.

And yet, when we think about what happens, we see that IL-23 is very prominently involved, of course as I mentioned, in the enthesis and enthesitis, but also in the skin. For example, damaged keratinocytes release DNA that simulates IL-37 that leads to plasmacytoid cells releasing interferon, that in turn effects other plasmacytoid cells to release IL-17 to drive T cells to go to lymph nodes that come back to the skin, and then to drive the IL-17 pathophysiologic role in the development of the psoriasis that we see. And in the gut, we looked at dysbiosis that affects all of this.

As I mentioned, in the joints the target is the enthesis, and we see how that is important to release IL-23, and that leads to the whole chain of IL-23, IL-17 events. There’s a lot more to this that is very complex, but that gives us an overview about what’s going on outside of the cell.

Now, what’s interesting is how IL-17 affects what goes on inside the cell. We’ve been focused on intracellular signaling in RA [rheumatoid arthritis], where we see IL-6 and other gamma chain cytokines that will allow for the JAK/STAT signaling intracellularly to cause DNA stimulation for further cytokine production. But in this disease, we’re seeing IL-17 that affects the TRF/ERK intracellular signal in cascade and chain.

What is important to understand is that there is an analogy of how all of these systems work, but there are different players in the system that allow for the clinical development of the disease that we see, which is the psoriasis, the enthesitis, the arthritis, and when there’s the inclusion of the gut, we have colitis. This gives a rather broad overview of what’s going on.

Thanks John, there’s definitely a complex interplay in our PsA pathophysiology. Moving on, when you think about disease burden and prevalence, particularly here in the US with psoriatic arthritis, variations perhaps in PsA based on gender, race, age, do they play a role in the prevalence? Hillary, can you give some insights into this please?

: Psoriatic arthritis affects approximately 1% to 2% of the US population, which is about 1 million adults, including about 30% of patients with psoriasis. There’s an equal prevalence between men and women, and the onset is generally between the ages of 30 and 50. But many patients remain undiagnosed for many years.

Most patients develop psoriasis first, but approximately 10% of patients will develop the arthritis first, leading to potentially further delay in diagnosis. Caucasians are more commonly affected, and psoriatic arthritis is less frequently reported in Asians, African Americans, and LatinX populations, but the distribution across the ethnicities has not been well studied.

Overview of Psoriatic Arthritis

Tagging along with that, quality of life [QOL] issues. Obviously, the burden of disease is quite prevalent. Can you give some insight into that, and some tools that are used to measure quality of life, maybe some PROs, patient reported outcomes, maybe used more in clinical trials, or things they use in the clinic?

: Psoriatic arthritis [PsA] affects quality of life in so many different areas. This affects physical health, mental health, ability to do activities of daily living, and just general well-being. There are tools that we use in the clinic. We don’t have as many measurement tools that we use on a consistent basis as we do in rheumatoid arthritis. In the clinic most people are going to be looking at a patient global [assessment] or a pain score. We’ll let Dr Feldman talk about if we’re measuring the skin in the clinic, then there are different instruments that are used for that. But when we’re looking at psoriatic arthritis as a whole, it’s generally going to be the patient global [assessment].

Now when we’re doing clinical trials, of course we’re measuring quality of life using things like the HAQ-DI [Health Assessment Questionnaire Disability Index], using FACIT-Fatigue [Functional Assessment of Chronic Illness Therapy-Fatigue], and these are really helpful when we’re interpreting clinical trial data.

 Anthony, if I could add one thing because Hillary laid it out really well. But I do think it’s important, and I believe Steve would agree with this, that from a patient’s perspective…as rheumatologists we focus on their joints and we acknowledge their skin. Maybe for dermatologists, at least some of them, it might be the other way around. But from the patient’s perspective, they have both. Both of those issues affect their QOL. And we may think that, well if they have a lot of [issues with] skin and not too much with joints, that’s more important than the other way around.

But I don’t think it’s always that way. It’s both of those issues affect their quality of life. And there have been some data generated to reflect that, and it does come into play when we take a look at some of the trials that we’ll talk about later.

Absolutely. Clearly numerous issues can play a role in what’s important to the patient. It’s important as health care practitioners that we recognize what’s truly affecting the quality of life, and that’s an excellent point, John.

John, I’ll go ahead and ask you since you so eloquently laid out the pathophysiology and alluded to this. We think about having comorbidities that would be associated with psoriatic arthritis. And related to that in some way would be, let’s say, the domains that the research group GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis] has outlined for us through the years in PsA. Do you want to discuss the GRAPPA domains, and also perhaps fill in the comorbidities that we associate with PsA?

: Let’s start with the comorbidities. We can start from the head and go down. There’s depression and significant fatigue that’s associated with the disease, reflecting central nervous system issues. There can be uveitis and iritis, conjunctivitis, and what have you. We certainly see psoriasis. The systemic effects on the cardiovascular system are immense. We’ve been discovering later than we did for rheumatoid arthritis how important these issues are for increasing the risk of MI [myocardial infarction], CVA [cerebrovascular accident], and heart failure, and arterial disease in general throughout the system with the metabolic effects in terms of there being the development of diabetes and the associated metabolic issues that are related to that. Then, of course, we have osteoporosis, and the arthritis, and the issues of colitis.

The burden of disease systemically is immense. And as I tend to think of it and tell people: Don’t think of it as psoriatic arthritis causing these manifestations. These manifestations and the arthritis and the psoriasis, they are the disease, the depression is the disease. And there is basic research that demonstrates how cytokines, for example, are inherently involved in depression and fatigue.

Those are the comorbidities. The GRAPPA domains are interesting, and they focus on the musculoskeletal and skin issues of the disease. They have been developed by GRAPPA, and they act as a guide in terms of identifying which areas of a given patient you want to understand are diseased, and how much disease, and then that might guide your therapy. But the domains themselves are things that I’ve already brought out with a couple of others.

We have arthritis; we have enthesitis; there’s dactylitis, which is the completely swollen digit, either toe or finger. Underlying that is the fact that the tendons, the full ray of the limb, are affected by the disease, and inflammation throughout the tendonosis and ligamentous structures allow for the sausage toe or sausage finger.

Then there’s nail disease, which is an extension of the tendon inflammation, because the tendons’ extension into the nail bed, it basically forms the nail bed. As a result it’s completely understandable why there would be nail disease in this disease, and Steve can certainly comment on that more fully.

We have all of these different domains, and the skin, of course I don’t want to leave out the skin. If you line them up in a row and you look at the GRAPPA guidelines in terms of the treatment of the disease, that allows for us, in a structured way, to understand how one can sort through which areas to treat and how different treatments may be chosen on the basis of what we know is effective.

 Steve,can you comment on that, particularly for the nail involvement? In PsA it’s mostly GRAPPA domains, but there is dermatology input as well; are the GRAPPA domains utilized or recognized by the dermatology community?

No. The GRAPPA domains would be thought of, at least within the world of dermatology, as something people might think about for their clinical trials and not so much for their clinical practice. In clinical practice dermatologists look at much more subjective assessments of their patients and treat accordingly.

Psoriatic Arthritis: Comorbidities and Quality of Life 

Steve, if you don’t mind, we’ll start looking on the dermatology side at the importance of early and, to some extent, accurate diagnosis in psoriasis. I know in my clinic, I have some medical dermatologists who I have a close relationship with to help me figure out if this rash I’m looking at, whether it’s classic or is truly psoriasis.

Can comment on the importance of that early and accurate diagnosis of psoriasis, or perhaps a regression from psoriasis to psoriatic arthritis, as Hillary pointed out, often the skin occurs first before the joint, can you tell us a little bit from the dermatology standpoint?

We talked about the skin, the joints, the other components of the disease. In terms of the skin, the diagnosis is very straightforward. We know it when we see it. And we don’t need to do a biopsy, we see the red scaly plaques and typical areas on the elbows, scalp, belly button, and nail changes that were mentioned.

The diagnosis of psoriasis for us is pretty straightforward. Patients come in for it, and when they do, we make the diagnosis.

Making the diagnosis of psoriatic arthritis is much more difficult. It seems to us that it’s difficult even for rheumatologists sometimes to tell whether somebody’s arthritis is psoriatic arthritis or not. It’s totally beyond my capability as a dermatologist to tell whether something is psoriatic arthritis or osteoarthritis, or gonococcal arthritis. You have 1 hot, swollen joint—I don’t know what it is, it could be psoriatic arthritis, it could be gonococcal disease, for all I can tell.

My role is to screen, to identify patients who might have psoriatic arthritis and get them to a rheumatologist early to identify the disease. We do tend to see the patients first because their skin disease comes up before the joints, and so we can make them aware that psoriatic arthritis is a possibility. My sense is most people with psoriasis don’t get psoriatic arthritis. That most people who do get psoriatic arthritis don’t get progressive disease, but sufficiently high numbers do that I need to get the person to a rheumatologist. I like to screen with very broad criteria: Are you having any joint stiffness? Any joint pain? Any back pain? If you have any of those I might tell you, “OK, well you can take some Motrin for now, but we need a rheumatologist to see you and evaluate you.”

My thinking on this is based on a study we did a few years ago where we asked rheumatologists, “When we dermatologists see somebody who has psoriatic arthritis, what should we do as dermatologists?” Now you can correct me if you think otherwise, but what I was told was, “Well start by doing a complete musculoskeletal examination, including range of motion and gait.” And I’m like, “No, I’m not doing that.” I’m sending patients to you. I wouldn’t know what laboratory tests to order, what x-rays to order, or how to interpret those x-rays if I did order them.

That’s interesting insight. If you were to perhaps ask our group, and I’m certain John and Hillary would agree, we would never expert a dermatologist, as I would not expect to be sitting there doing skin biopsies or PASIs [Psoriasis Area and Severity Index scores] outside of clinical trials. But as you’ve mentioned, there are a number of tools that are trying to be developed and hopefully easy tools that are simple.

You also brought up back pain, which I thought was important as well. Not that we want our clinics flooded with degenerative disk disease or lumbago, but any hint of back pain in a 22-year-old that’s been going on for years….

But even that level, this is our job to figure that out for you. I agree. I’m not sure who told you to do a musculoskeletal exam, you wouldn’t have time for it, and honestly, that’s on us. I agree with how you were handling it before.

I told the rheumatologist, “I’m not going to do that, I can’t do that.” And he said, “Well, you went to medical school, Steve, you learned to do those things.” I believe in the golden rule. If rheumatologists ask dermatologists, “What should we do to examine the skin,” the first thing we would tell you is, “Do a complete skin examination, top to bottom, every area,” and I’m pretty sure most rheumatologists would go, “No, that’s OK….”

I think depression is also common enough that I have a role to screen for depression, and I don’t do that in any formal way. If I see a patient sitting there like this, then I know they are probably depressed and I need to get them to seek some help.

Then there are the cardiovascular issues, and I don’t even screen for those, and I wonder how big an issue those are. If you’re between the ages of 20 and 30 and you have severe psoriasis, you’re at something like a 2- to 3-fold increased risk of having an MI [myocardial infarction], which sounds horrible. But then if you ask yourself, well what’s the chance that a 20-to-30-year-old without severe psoriasis is going to have an MI? You realize, well, it’s pretty close to zero. And 2 to 3 times close to zero is still close to zero. Maybe there is some cardiovascular importance, but we have to be careful and consider it objectively and not emotionally.

That input from dermatology is very helpful. We do try to play a role as not just rheumatologists. Clearly I don’t manage, let’s say, cardiovascular risk or depression, but as you pointed out, when it’s identified, it’s fairly common in the patients that we see. I know that you see it as well, potentially increased risk of depression and suicide, we make sure these patients get into the right hands.

The cardiovascular risk, you’re right, for younger patients, if it’s an inflammatory disease, we want to talk about psoriatic today obviously. We do recognize that increased cardiovascular risk; clearly if there’s issues with diet, exercise early on, the traditional cardiovascular things you try to improve, that’s important. But this disease also does play a role irrespective of the traditional risk factors. But that’s helpful from a dermatologist’s standpoint. What’s key in this discussion is that interplay between rheumatologists and dermatologists. And we may not have official rheumatology/dermatology clinics in all of our community or academic practices, but having that relationship between a good medical dermatologist and rheumatology is critical.

Early Diagnosis of Psoriasis and Psoriatic Arthritis

We’ll move into discussion on diagnosis and standard of care, and try to hit on both, the rheumatology perspective and dermatology perspective.

We’ll start out with Hillary on this. Hillary, if you don’t mind, talk about the clinical manifestations of psoriatic arthritis; in your clinic, how a typical psoriatic arthritis patient may present.

: That’s one of the challenges of psoriatic arthritis, that there is no typical presentation of this disease. This is such a heterogeneous disease, and as we mentioned before, most patients are going to have psoriasis prior to developing the musculoskeletal manifestations. But about 10% of patients, or in my practice that’s even higher, will present with a hallmark of the disease from an arthritis aspect, but they just don’t know they have psoriasis. And sometimes, as we know, they do, and it’s in their ear or their scalp or their gluteal crease, and they’re not aware that’s psoriasis. This can be really challenging.

Oftentimes in rheumatology these patients are going to present to us with joint paint. That’s the most typical feature. But we see some of these other very classic features, such as enthesitis or dactylitis.

I had a young patient come in in her early 30s, and she had very severe dactylitis in a couple of her toes, and she was having trouble walking due to this but no known history of psoriasis. She later found out that there was a family history.

We see the patients also with joint paint. This is not as often symmetric the way that it is in rheumatoid arthritis. We see enthesitis. Patients often don’t realize that the tenderness at their elbows or at their Achilles is actually inflammation of where the tendons and ligaments connect to the bone. The sausage digit, dactylitis of the fingers and toes. Patients can present with very severe nail disease. I’ve had a couple of patients where that was actually their primary issue, that their nails were very affected. And we don’t talk too much about nail pain, but pain can go along with nail disease.

And axial involvement. We always need to be evaluating for whether patients have sacroiliitis that goes along with their psoriatic arthritis. This is different than AS [ankylosing spondylitis] axial involvement, and sometimes patients don’t have as much pain that goes along with it, but it’s something that we need to look at.

Then of course the other systemic manifestations, fatigue and depression, are real issues in this disease. And as John mentioned earlier, these are not just secondary to the disease, but these actually can come primarily from inflammatory cytokines and are part of the pathophysiology of psoriatic arthritis.

It’s a very heterogeneous presentation, and we all have that bucket of patients where we’re pretty sure it’s psoriatic arthritis based on some of these hallmark findings, but sometimes it takes a while for this disease to really declare itself.

 The true heterogeneity of this disease is quite remarkable.

Clinical Manifestations of PsA 

John, in your clinical practice, are there any tools that you use to diagnose? There are obviously physical exam findings, histologies, and imaging.

As we go over clinical trial data about the CASPAR [Classification Criteria for Psoriatic Arthritis] criteria, what role does that play in the clinical setting outside clinical trials in your diagnosis algorithm?

 Let me put this in the context of what we do in a drug study with patients. I go into an exam room with my coordinator to do the psoriatic arthritis measurements, and I come out exhausted. I must do a full joint count. I must check all the entheses to do an enthesitis index. I must do a PASI [Psoriasis Area and Severity Index] score by identifying all the lesions in the general area and all the aspects of the skin, with the erythema and desquamation. Then I have to do the NAPSI [Nail Psoriasis Severity Index], which looks at all the nails and the pits, onycholysis, and desquamation, and the grumbling. You get the picture.

That’s what we do in a clinical trial. But when I’m seeing a patient in the clinic, I’m examining all the joints, unlike Steve who just can’t bear to think about doing something like that. I’m checking all the enthesitis areas.

Interestingly, after you’ve done this for many years, you can do this very quickly, but you do have to remember to pinch the Achilles tendons. Because if you don’t pinch them, you won’t actually elicit the tenderness that a lot of patients have and that they don’t realize that they have. You have to look at the toes, the fingers, and the skin. You can do this reasonably quickly, but you don’t measure it.

As far as blood work, we look at acute phase reactants with SED [sedimentation] rate and CRPs[C-reactive proteins]. We measure an HLA-B27 realizing that it doesn’t add that much in terms of the diagnosis. If it’s there and there’s a clinical suspicion for the disease, it supports the diagnosis. And if it’s not there, you know, not think about the diagnosis anymore.

Imaging is important, and certainly getting x-rays of hands and feet you can pick up subtle or major issues related to erosions, but also particularly new bone formation. Because that element right there distinguishes the radiological features of PsA vs RA [rheumatoid arthritis]. In RA you never see a bone formation. Consequently, that helps to make a distinction. That is 1 of the criteria for CASPAR in terms of diagnostic criteria.

But before I get to those, 1 last thing I want to say about imaging is that we have employed ultrasound in a systematic way. And ultrasound of the hands, and particularly the feet, is helpful. For our ultrasonographer, a person who reads the images, we have a technologist who does them. He picks up amazing things, and particularly for the tenosynovitis, and particularly in the feet and the Achilles tendon. That is invaluable because you don’t know what we’re missing when we’re doing a clinical exam.

That brings me to the discussion about the CASPAR criteria. Let’s remember these are classification criteria, they’re not diagnostic criteria. The only diagnostic criteria we have in rheumatology are the Jones criteria for rheumatic fever.

The CASPAR criteria are interesting because it’s a weight-based composite score, and you weigh different components. The element that is the most critical and the most important is that before you apply the criteria, the patient must have, on examination, an element of inflammatory musculoskeletal issue. That’s either synovitis, enthesitis, or dactylitis. If they don’t have that, at some point during your examination, or if you’ve seen them over a period of time, you can’t utilize the criteria. That’s the stopping point.

If they have it, then you start looking at whether they have skin involvement. Right then and there, psoriasis to get a couple of points. If they have enthesitis, they get a point; nail disease, a negative rheumatoid factor; and new bone formation on an x-ray.

Then you add up the points. If they have 3 points or more, they have met the criteria for the CASPAR classification. Now what’s the importance of that? That person would be able to go into a clinical trial. If someone doesn’t meet the criteria, that doesn’t mean they don’t have a disease, as Hillary [Norton] pointed out. It can be very tricky, very subtle, and therefore, you can make a clinical diagnosis on the basis of what you have in front of you, but you may not be as sure about it if they don’t have many of these clinical clues.

These criteria, classification criteria, like any classification criteria, act as a guideline. They act as something against which you take the elements and you can apply them to any patient you see, then at the end of the day you make your clinical judgment as to what’s going on.

 With the CASPAR criteria, as you point out, sometimes it’s not recognized or mentioned. But as you point out, there are joint-, entheseal-, and spine-based inflammatory processes. One of those must be ongoing to be part of the CASPAR criteria. As you said, the diagnostic strategy pointed out what you do in a clinical trial is helpful. You walk out exhausted doing these trials, but over time—even outside clinical trials—there are things you can do in a fairly regimented fashion.

Diagnosis of Psoriatic Arthritis

Let’s go on to the dermatology side. Steve, talk to us about goals of therapy. Are there any factors that guide your selection in a patient with psoriasis, whether they have comorbidities, have tried therapy before, or have severity of skin involvement. Can you comment on that?

On the skin side, my goal of therapy in patients with psoriasis and psoriatic arthritis is to make patients happy. The National Psoriasis Foundation has treatment target goals to get people completely clear with less than 1% of their body covered. But in my practice, if the patient is happy, I’m happy. My goal for psoriatic arthritis is for that to be controlled and for them not to have joint destruction, and I’m going to achieve that by sending them to 1 of you all to take care of them.

There are so many treatments for the skin that it’s hard to choose, and there are overarching classes like topical therapies that we use for patients who have limited disease. Ultraviolet light treatment takes care of the skin without affecting the internal immune system, and then [we use] systemic drugs. To a large extent, I’m relying on patient preference.

If somebody just has a couple of spots, topicals make sense. If they’re covered, then I have to do more than topicals, and there’s some middle point that is highly dependent on the patient. If they feel, “I cannot put topicals on all my spots,” then we must move on to phototherapy or systemic treatment. And you probably don’t have light boxes to offer your patients, but there may be tanning beds in your community. In theory you could even recommend light treatment to patients for their skin disease.

There are so many dimensions to consider among therapies, and 1 therapy is not better than all the others on all the dimensions. And patient preferences for different aspects of treatment may vary from my preferences, so choosing a therapy is something I have to do in collaboration with the patient.

 Absolutely. Hillary, from the rheumatology standpoint, same question. [What are your] high-level overview goals of therapy, thinking about comorbidities and prior therapies? Walk us through psoriatic arthritis.

 I like how Steve touched on the shared decision-making of the patient, because we’re talking about that a lot more in rheumatology these days. Patient preference comes into this so much. But in terms of guiding the patient when we’re talking about goals, we’re thinking about controlling inflammation and pain and preventing joint damage. We’re also thinking about treating their skin, preventing disability, and fatigue, and these other PROs [patient-reported outcomes] have historically been a cringe-inducing thing for rheumatologists because fatigue is so multifactorial. Many of our patients have depression as well.

We’re getting data from our clinical trials on our therapies, but we can improve fatigue. As John mentioned, we know that this is cytokine based; it’s part of the pathophysiology. We’re thinking about the whole picture.

And then comorbidities. You mentioned that Anthony. Many of these patients are at risk for other things, like uveitis and inflammatory bowel disease. We’re taking that into account when we’re selecting a therapy.

Our treatment is going to be guided by the domains that are involved with psoriatic arthritis. We are going to be thinking in terms of those guidelines that we have: Do they have primarily severe skin involvement? Are their joints more severe? You know, dactylitis, enthesitis. We’re going to be thinking about what is front and center for that patient when we’re choosing a therapy.

And disease severity definitely plays into it. We’re going to be looking at markers for poor prognosis and rapidly progressive disease. Many joints involve these types of things when we’re assessing severity and choosing a therapy.

 As Steve mentioned, all these entities should be shared decision-making with the patient. In this disease, it’s clearly a challenge. But there are plenty of therapies, and trying to tailor the therapies to the patients’ needs and expectations is important.

John, looking at these therapies, we have a number for psoriatic arthritis. Can you touch on the importance of optimal timing of therapeutic intervention for effectively managing the psoriatic disease? What’s important to get the patient into a clinic and onto appropriate therapy?

 It’s fair to say that most of us optimally would like to have the ability to diagnose a patient with relatively new-onset disease. The opportunities to do that are not high. Oftentimes patients are coming to us with years of disease. As a result, we’re losing out on that new window for the disease. Does it make a difference? It does, although from the trials that we’ve looked at over the years, the progression of joint damage is gold standard the ability of a disease to account for deformity and disability. For most patients, the progression of x-ray damage in psoriatic arthritis is not as rapid as it is in rheumatoid arthritis. Obviously, you always have individual patients for whom things might be different. Nonetheless, it’s fair to say that as soon as we diagnose a patient with the disease, we want to institute proper management as quickly as possible. We want to institute that therapy in such a fashion that we follow them closely to determine if the patient is responding. If they are not responding, then we advance therapy in a timely fashion.

This is a treat-to-target approach, in my mind. It’s not as fully developed and welcomed by rheumatologists for this disease as much as it is for rheumatoid arthritis, and one can even wonder about that.

The concept of starting therapy, seeing if a patient responds, and changing their therapy if they’re not is extremely important. It’s important because we want to give our patients optimism that we can get control of the disease and get them to a much better place. But if we don’t approach this in a step-wise fashion and use this optimal-timing approach, sometimes they just get fatigued at what we’re doing and stop coming and adhering.

 Understanding their expectations, this concept is getting our patients into us and into dermatology for active diagnosis as soon as possible.

Goals of Therapy in Psoriasis and Psoriatic Arthritis

Steve, can you share treatment options with nonbiologics and DMARDs [disease-modifying antirheumatic drugs] that are used in psoriasis and in psoriatic arthritis.

Talk to me specifically about DMARDs such as methotrexate, apremilast, hydroxychloroquine. In the dermatology community, can you tell me examples when these DMARDs are used? What is your experience overall with them?

 Most patients with psoriasis have very mild disease. If you’re taking care of psoriatic arthritis and have a few little spots, I don’t know if we think of them as DMARDs, but topical therapy would be the way to start. We typically start with a very high-potency topical steroid, like a clobetasol or a betamethasone dipropionate, in an appropriate vehicle. Maybe an ointment if they’re willing to use it on elbows and knees. Solutions for the scalp. They work great if you put them on, which is huge. Compliance and getting people to take their pills is hard enough. Getting them to rub slop paste in their hair and onto their scalp is like the mother of all compliance problems. Compliance is ridiculously poor to topical therapy. But if you get people to do it, it does work well.

The next whole class we shouldn’t forget is that phototherapy I mentioned earlier. Dermatologists would be happy if you sent patients for ultraviolet light treatment. If you felt like the patient had psoriatic arthritis without joint destruction and you were thinking, “I can give them a nonsteroidal anti-inflammatory, but they have skin disease,” you might want to refer them to the dermatologist who might use topicals or phototherapy to manage the skin disease. They might not need a biologic.

If they do need systemic therapy, what do we have? In the old days we had methotrexate and cyclosporine, and they seemed reasonably effective. Cyclosporine, if you gave enough of it, would clear patients up. But psoriasis is a chronic disease, and cyclosporine is not something that dermatologists want to give [these] people.

For us dermatologists, our idea of adverse events that we are concerned about is when an acne patient gets dryness from the topical therapy we prescribed. Cyclosporine is not what we want to be giving people, even methotrexate. You all probably think methotrexate is like water. But to us, it’s 1 of the most serious drugs we prescribed.

 We shouldn’t forget oral retinoid therapy, which is another 1 that you probably would never use for joints. But it might be an effective way of improving pustular disease of the palm and soles and making phototherapy and topicals more effective. Then we have apremilast, the phosphodiesterase-4 inhibitor. It’s not the most effective drug, and it’s not the most well-tolerated drug because 1 of 6 people get diarrhea or headaches. But from a serious adverse-event standpoint, it seems safe. Many people in dermatology think of it as the marijuana of systemic therapies for psoriasis. You know, it’s the gateway drug. Let’s start with this. We don’t have to do any lab tests, we don’t have to do monitoring. I don’t know that you have to use it that way. I feel comfortable going straight to more effective therapies that are even better tolerated.

 Steve, can I ask you about light therapy? Do you and your colleagues have concerns about long-term effects of malignancy issues due to phototherapy?

 Gosh, yes. Studies done at the Mayo Clinic with office-based UV-B phototherapy were with and without tar, which is another carcinogen. With 30-year follow-up, there is no detectable increased risk of skin cancer with UV-B phototherapy. With UV-B phototherapy, I’m sure there must be some increased risk, but it’s small. PUVA, psoralen plus UV-A light, is more carcinogenic, and we hardly use that anymore now that we have many good systemic therapies for the disease.

Dermatologists feel pretty comfortable telling patients with psoriasis to go out in the sun. We use home phototherapy. Dermatologists think I’m crazy when I recommend tanning beds because they think about, well, what do we see with tanning beds? We see skin cancers. But the vast majority don’t get skin cancer. The UV-A light and the UV-B in most tanning beds are perfectly adequate for treating psoriasis in many patients. In fact, it’s probably the most common form of phototherapy that patients use.

Nonbiologics: Treatment of PsO and PsA

Let’s discuss the biologic or advanced therapies that are available for psoriasis and psoriatic arthritis. Interestingly, when these first came out in the TNF [tumor necrosis factor] world, some were for psoriatic arthritis and then got approved for psoriasis. Then just the dermatologists had this trend that psoriasis has been the first indication, followed by psoriatic arthritis, to go beyond the discussion we’re having today. We’ll start by naming the classes or the mechanism of action [MOA] families and then the individual therapies. We know that TNF inhibitors, including golimumab, certolizumab, adalimumab, are the initial therapies, the go-to therapies, and for some they remain for our psoriatic arthritis and their ability to cover the gamut.

The second MOA family, obviously the interleukin-17a inhibitors, is currently available: secukinumab and ixekizumab, which are both approved for psoriatic arthritis and psoriasis. More recently approved for us in the rheumatology world—dermatologists have it for similar use—is guselkumab, the IL-23 inhibitor. Prior to that was the IL-12/23 inhibitor of ustekinumab. For a high-level overview of T-cell costimulatory blockade of abatacept and a Janus kinase inhibitor, tofacitinib is the only drug approved for PsA [psoriatic arthritis]; others are likely to come out. Those are the 5 families, or 5 mechanisms of action. We’ll start with very high level key points on efficacy and safety of these various classes of drugs in psoriatic arthritis. If it’s OK, Hillary, we’ll start again giving the broad TNF umbrella. Can you go over some of the key points? Is there any difference among them in the treatment of psoriatic arthritis?

 We have extensive experience using the TNF inhibitors for psoriatic arthritis and for psoriasis. These have been primarily the go-to biologics for many years prior to getting our newer therapies. We do have data for all the different domains for TNF inhibitors, so we know they treat the peripheral arthritis, axial disease, dactylitis, enthesitis, and nails. That is important in our guidelines to tell us to start with TNF inhibitors after patients have done DMARDs [disease-modifying antirheumatic drugs] or, in some cases, gone directly to TNF inhibitors in the case of axial disease. This is where we really take the comorbidities into account because if somebody has inflammatory bowel disease or uveitis, we might want to use a monoclonal antibody because we’ve got data there.

There are safety issues. This is where we’ll talk about safety advantages with more therapies, because we have more options. The TNF inhibitors do have a box warning for infection and malignancy, and there are some other issues. For decompensated heart failure or a history of demyelinating disease, we don’t want to use TNF inhibitors. There are a lot of advantages. We have to take into account that particular patient and their comorbidities and safety issues for the newer therapies that are starting to come into play.

 Thank you. John, similar question: Can you give us an overview about the safety of the class, the interleukin-17a inhibitors? Can you touch on that?

 It’s remarkable what’s happened in the last 5 years or so in this space. We had only TNF inhibitors as advancements on top of our conventional DMARDs, and now we have all these others. The 17a inhibitors were the first ones after the TNF inhibitors, and we have 2 that have been approved that you alluded to: secukinumab and ixekizumab. They are effective for the psoriatic arthritis component of the disease, but they’re not more effective than TNF inhibitors. In fact, when we look at psoriatic arthritis, we see that with the newer agents that are demonstrating incredible effects on skin, we still can’t break that barrier of joint improvement, the same barrier we’ve hit with rheumatoid arthritis [RA].

What’s incredible is what happens to the skin. As Steve knows very well, we’re seeing PASI [Psoriasis Area and Severity Index] scores, we’re talking about PASI scores of 90%, even 100%. PASI 90 scores of 70-plus percent improvements. But for joint improvements, ACR20 [American College of Rheumatology 20% improvement], ACR50 [American College of Rheumatology 50% improvement], and 70 [American College of Rheumatology 70% improvement] are not much better than the mid-50s, 30s, and about 20, which is what we’re used to. They’re effective, and sometimes you hit a home run—somebody gets an incredible response with their joints. But most people going on them are going to get this average response.

As for their safety, this is really a feather in the cap of this class. They are safe agents. There are a couple of things we must be aware of. There are the few patients who may develop colitis or may, if they’ve had a history of colitis, have an exacerbation. It is important to exercise caution and not take someone with active colitis. But it is not wrong or contraindicated to try to use them if someone has had a history of colitis, but just watch them very carefully.

The only other minor thing called out in the label of the drugs—and they don’t have a black-box warning about them, which is important—is the issue of fungal infections. It’s not a huge issue. It’s something in the background that one needs to be aware of and monitor. Accepting for other tolerability issues and other issues like minor infections and such, these agents are very safe and are definitely a welcome to our armamentarium to treat the disease.

 It has provided that effectiveness from a skin perspective but also for the TNF experience with the manifestations. Touching on the Janus kinase and even the T-cell costimulatory blocker, I consider these discussions to make this a comprehensive program. I say that specifically with abatacept. I’m not commenting on how to use or not use. But in my opinion, it came out with very little fanfare in the summer of 2017, when the abatacept article came out. There were 400 psoriatic arthritis ACR scores in the 40% range, compared with placebo in the 20% range. Safety was no different in PsA from what we saw in RA. I just want to throw it out to John: Was there much fanfare with abatacept when it came out for PsA?

 No. It was approved about the same time the IL-17s were taking off and everybody saw the data there.

 Tofacitinib had been the first JAK approved for psoriatic arthritis and they had a far more structured approach with 2 separate trials: a TNF experience and TNF naїve. I’ve seen good data on joint at the lower dose. Of course in early 2019, the FDA was sending out letters for us to keep an eye out for oral surveillance, which may have had somewhat of an effect on usage. But some rheumatologists felt that tofacitinib has been a helpful player in the armamentarium of psoriatic arthritis. Any comments on that, John or Hillary, with regard to the Janus kinase use? What’s available in PsA in your world?

 My thoughts in general are that they take a second. At least tofacitinib has taken a second line to the newer agents that have come out. I wouldn’t choose tofacitinib as a first therapy after conventionals over TNF or IL-17s. I would probably try both of those first and then go to that if I needed to. Except for 1 thing, which is your decision-making. If a patient wants a pill, the patient should get a pill.

 Absolutely. That’s where it plays the biggest role in my practice. This is not something I’m going to reach for first or second line. This is something I’m going to use if the patient fails multiple therapies and we’re looking for another MOA. But patients do sometimes request it simply because they want an oral agent.

Management of Psoriatic Arthritis With Biologics

 Let’s move on and go to the dermatology side and discuss factors we consider when choosing 1 biologic or advanced therapy class over another in your psoriasis treatment paradigm? Can you comment on that?

The major things I’m considering are safety, efficacy, and what’s feasible for the patient to get. The slight infection risk that you see with TNF [tumor necrosis factor] inhibitors is a reason for me to choose other medications. That uncommon inflammatory bowel disease, exacerbation or new onset with IL-17 blockers makes me lean away from those toward IL-23 blocking drugs. But if the insurer says, “You prescribe whatever you want, but we cover only this particular TNF inhibitor at this point,” then the patient and I will probably choose for them to take that.

Patients’ previous experience with particular classes affects my decision. If they did really well—safety and efficacy were there on a particular class—but that drug eventually stopped working, I may choose another drug from that class for them again. Patient preference is huge, but it’s gotten to the point that there are so many options that the patients can’t choose and they’re relying on me. It’s like the studies that have been done about giving people too many jelly choices in the grocery store; they can’t choose.

This idea of the pill is really fascinating because some patients do come in who saw an ad on television for a pill, so they ask about it. Or if they’ve never been on an injection before, they’re afraid of injections. One way I could get over that is to let them know the medication, “I’ve got a great drug for you that’s very safe, very effective, but it’s given by injection like diabetics take insulin. You know how patients take insulin 2 to 4 times a day? Well, it’s not exactly like insulin, you only have to take it once a month.” If I start by telling patients it’s an injection once a month, their brain compares once a month with not taking an injection, and they don’t want to do it. If I somehow first anchor them on the idea of injections daily or twice a day, then when I tell them it’s once a week, or 1 a month, or every 3 months, they don’t mind nearly as much.

 That’s very helpful advice. Patient preference can play such a role. And it’s a unique situation that we have a number of therapies, albeit with insurance playing a role in those decisions. But it’s helpful that we have these in our armamentarium.

Approaching Treatment of Psoriatic Arthritis 

We’ve talked about some of the classes. Let’s take a deeper dive into interleukin-23 inhibitors. For us in rheumatology, this approval has occurred over the past several months. Dermatology has had it for years. John, I’ll start with you. Guselkumab is the first approved among the IL-23 inhibitors for treatment of adults with severely active PsA [psoriatic arthritis]. Can you go over the study design of DISCOVER-1 and DISCOVER-2, the pivotal phase 3 trials and the clinical trial program for PsA? Perhaps discuss some key outcomes and the patient population in those 2 studies.

 This is an interesting class, the anti–IL-23 class. In my brief discussion about the pathophysiology of the disease, I tried to point out how important this cytokine is. We think of it as upstream from IL-17. What’s interesting in the history of IL-23 in terms of our treatments is the IL-12/23 ustekinumab, which has pretty good skin effect and not very good joint effect. It never was used often in treatment of psoriatic arthritis, but it’s quite good in colitis. With IL-23 alone, where the P19 subunit is hit by the monoclonal antibody, we’re seeing a differential effect.

There were 2 phase 3 studies that led to the approval of this drug by the FDA. Dr Philip Mease was the first author on the publication of DISCOVER-1, which was a combination population in which they allowed patients who had been on 1 to 2 TNF [tumor necrosis factor] inhibitors to go into the trial. About a third of the patients were TNFexperienced for this study. For Dr Atul Deodhar’s paper, which came out in 2020, both publications are in the 

, this DISCOVER-2 trial was a pure TNF biologic-naїve population.

There were about 400 patients in these trials. They looked at similar outcomes in terms of ACR20 [American College of Rheumatology 20% improvement], 50, and 70s, and PASI [Psoriasis Area and Severity Index] 75, 90, and 100s. They looked at enthesitis scores and dactylitis scores, quality-of-life measures. In both trials they did something quite different from what we’ve seen. They tried to get at the notion and interrogate the elements of spondylitis in the psoriatic arthritis populations. They allowed the investigator to identify every subject as having or not having spondylitis on the basis of a history of the elements of inflammatory back pain and then also on the basis of current or historical sacroiliac films that would demonstrate spondylitis. Then they looked at the results of these patients in terms of the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index] scores. This was very intriguing.

With all that being said and all those elements being evaluated in the course of the trials, there was 1 other factor that was looked at: fatigue, which is not unusual. But they looked at the pro-fatigue FACIT[Functional Assessment of Chronic Illness Therapy] score as a prespecified outcome—not a primary outcome but a secondary outcome. Because of the results of that, fatigue data were allowed in the label of the drug. What was disappointing to me is that they didn’t look at NAPSI [Nail Psoriasis Severity Index] scores, nail involvement scores. I was surprised about that. I would like to have seen those data. We all want to know if the drug really works for nail involvement.

DISCOVER-1/2 Trials in PsA

 Hillary, I’ll let you address the safety and efficacy profile from the results of those trials.

 Guselkumab did demonstrate joint efficacy in both the bio-naїve and bio-experienced populations in terms of the ACR20 [American College of Rheumatology 20% improvement]. And we saw robust ACR20 scores in DISCOVER-2, which was the bio-naїve population, so ACR20 scores of 20%, which is strong for joint scores and even higher out at 52 weeks. I believe we were getting above 70% at 52 weeks. Skin efficacy, in terms of investigator global assessment, was 0 or 1; those are high skin scores. I’ll let Steve speak to that, but there was very high skin clearance and, as John mentioned, improvement in self-assessment of sacroiliitis in terms of the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index]. That was an interesting way to do this. Patients did have documented sacroiliitis either by history or by an x-ray at the time of enrollment in the trial. This was a self-assessment. This is a different way of doing this, and we can talk more about that.

Also, we saw improvement in the patient-reported outcomes as measured by the HAQ-DI [Health Assessment Questionnaire—Disability Index], FACIT [Functional Assessment of Chronic Illness Therapy] fatigue, and SF-36 [Short Form–36]. This was the first time the FACIT fatigue was included in a label. This is significant for our patients because fatigue is quite a concern. We saw improvement in dactylitis, and we saw improvement in enthesitis, so we’re really covering all the bases except for, as John mentioned, a NAPSI [Nail Psoriasis Severity Index] score.

When we look at safety, that is where this really shines. When all of us first saw these safety data we were impressed. When we look at serious adverse events, there were more in the placebo group than there were in the treatment group. That speaks to the immune dysfunction or dysregulation in untreated disease or undertreated disease compared with well-treated disease. We always have to take the disease state into account. But there are very similar infection rates in the placebo group compared with the treatment group. All of this is painting a picture of efficacy in terms of both joint and skin, as well as the other PsA [psoriatic arthritis] domains, with a really strong safety profile.

 At the meeting there’s an abstract and a presentation from the MAXIMISE trial, which is the secukinumab trial, which is a prespecified prospective trial looking at spondylitis and psoriatic arthritis population. Just to let everybody know that now we have some controlled data allowing us to understand how these agents work in the spondylitis patients with PsA.

 Exactly. By no means is this the only stab looking at it. I’d say perhaps this is the first. In subsequent trials it has set the stage for future looks into this. There’s not 1 perfect way of doing this. But as you were saying, in this meeting and in subsequent meetings we’ll see more data.

Safety and Efficacy of IL-23 Inhibitors for Treatment of PsA

Hillary, going back to the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index] from the DISCOVERY trials, how should that be interpreted? Is there relevance in your clinical practice?

 This is a different approach because we’re not using some of the direct investigator-driven assessments of spondylitis. BASDAI is a patient survey, and we’re asking questions about fatigue, about spine pain, joint pain, enthesitis, and duration and severity of morning stiffness. This is something that’s been validated, and we commonly use this in our clinics even when we’re not doing clinical trials. The numbers looked good. I mean, this is an interesting way of doing things, particularly when we looked at the BASDAI 50; that’s a more stringent outcome measure. We’re looking at a 50% improvement, and about twice as many of the patients getting guselkumab had achieved that BASDAI 50. This is intriguing. This is not a complete look at sacroiliitis or axial involvement by any means, but this gives us some reassurance when we have patients with that domain of activity, and we can address that.

 That’s helpful. John, just a quick comment. It seems as if we’re bringing up the fatigue scores, and yes, this is unique in these studies. This was in the label. Specifically for pain and fatigue and with the recognition of rheumatologists’ experience with IL-23s in the clinic outside clinical trials may be somewhat limiting because of the recent approval for PsA [psoriatic arthritis]. Specifically for fatigue and maybe for pain as well, how do the clinical trial outcomes for pain and fatigue relate to your experience so far with using IL-23 inhibitors in your patients with PsA? Is there a correlation from what you saw in the trials vs what you see in the clinic?

 You laid the groundwork here. This drug was approved for PsA only in early July.The amount of experience that I’ve had has been relatively limited. I was an investigator in the trials, and therefore I can comment about the open-label phase where I knew the patients were getting the drug and how they were feeling and rating these elements, and they were doing very well. It’s going to take another amount of time if we’re going to be able to comment about these issues in terms of the population that we’re seeing clinically. Hillary, have you had more of an opportunity to see patients on the drug?

 Yes. I have a number of patients on the drug, and the thing that really struck me first was the skin clearance. My first patient who took this drug was a young man in his 30s, and he had had psoriasis his entire life. He never remembered not having psoriasis, and he had been on several agents. When I told him I thought we could get his skin cleared, he didn’t really believe me. He came back, and on his first visit his skin was clear and he was just amazed. That was my first experience with it, the rapid skin clearance. Since then we’ve had good results with joints as well. I’m liking the safety, particularly during this time, when patients are really even more concerned about infection than ever. This is very timely for us to have this option.

Impact of IL-23 Inhibitors on Pain and Fatigue in PsA  

: On the dermatology side, can you give a high level overview for all the agents, Steve, with regard to how they can be used as monotherapy? Can you combine biologics with different MOAs [mechanisms of action]? Is that done in dermatology? Give us some insight into that.

: For monotherapy, that’s the easy one because the answer is absolutely. We can use them as monotherapy. All the clinical trials in psoriasis, the drugs are tested as monotherapy. I look at psoriatic arthritis [PsA] studies, the biologics, half the patients are on methotrexate, and 10% to 20% might be on systemic steroids. In the psoriasis trial all those patients are excluded. We’re only looking at monotherapy data, so we know the drug is safe and effective as monotherapy. If I did want to use a biologic in combination, I’m relying on the rheumatology safety experience and your trials, not on anything from actual psoriasis studies.

Combining biologics is another question entirely. I don’t know that you need to do it very often because with IL-17 [interleukin-17] and IL-23 blockade and some of the better TNF[tumor necrosis factor] inhibitors, I have 9 out of 10 patients who are getting fabulous responses with monotherapy. It would be an unusual patient who needed to get 2 biologics at once. But I have them, and they’re suffering horribly, and when I need to, yes, I’ll give 2 biologics at one time if I can get it approved or covered in some way. So far it seems safe, but the numbers of patients are so small that I wouldn’t put a whole lot of confidence in my understanding of their safety.

 If you were to ask the rheumatology community, I don’t want to speak for our other 2 panelists, but the answer to that question, specifically the word biologics, the answer is no. In rheumatology we learned a lesson with our trials, this was years ago combining 2 different mechanisms. Again, we can’t compare that experience to PsA, but increased risk of infection, much less the ability to get it covered, led us to not combining biologics. The question could be asked, could phosphodiesterase, which is not a biologic, it’s a small molecule, be combined with an IL-17? I’m often asked that, and I’m really amazed at kind of the diverse answers I get.

I put it back into the audience and ask them, are you doing it? I personally do not, not just because of the prohibitive cost, but I would want to see data on that. What’s the safety with phosphodiesterase? But with regard to the effectiveness of doing so and seeing a trial with those two, I’m not a big fan of combining. Plus we have so many available MOAs now that hopefully we can find 1 and only 1 that will be healthy for our patients. Again, I don’t want to speak for all rheumatologists, but with regard to the word biologics, very rarely do I think we’d see that in a rheumatology community.

Biologics in PsA: Monotherapy vs Combination Therapy

 Steve, while I have you and we’re wrapping this session up, let’s talk about switching therapies. Under what circumstances in the dermatology world for psoriasis would you switch therapies? Obviously, lack of effectiveness or tolerance. And when you do switch, do you stay in the same class or do you switch to other classes?

 I switch when the patient feels like they’re not getting enough efficacy or if they’re having some adverse event, maybe if they don’t tolerate the treatment. It must be more than a mild lack of efficacy. They’ve got these treatment to target guidelines that say I should be getting patients clear. If the patient is happy on a drug that made them a lot better but didn’t get them quite close to clear, I’m not going to change their therapy. The patient must be quite bothered by their residual disease to make a change from a drug that helps and isn’t causing [adverse] effects to one that I don’t know if it’s going to work and it may cause a significant adverse effect. Once they’re already on something and it’s helping, and they’re doing OK on it, I have a reluctance to change therapies.

When I do change, it depends on whether it’s primary or secondary failure. If I put them on an IL-17 [interleukin-17] class and it doesn’t work at all, then I’m likely to switch them to an IL-23 blocking drug. If I put them on an IL-17 drug and it works great, and then a year or two later it stops working, I feel like an IL-17 works great for them until they develop an antibody against it, so I should go back to another IL-17 drug.

 Helpful. John, from the rheumatology standpoint, one of the most challenging consults I’ll get from medical dermatologists, who are, I won’t say risk averse or switch averse, which honestly I’m in the same boat, Steve, as you. I’m not a big fan of the flip-floppers, and you’ll see these patients who have been on 4 or 5 biologics in the course of a year, and I’m like, wow, what’s happening here? With that being said, John, when you get that consult from dermatology and they say, “Look, the skin is doing great, their gut’s not been an issue, they’re on this drug, and they had some joint complaints that didn’t seem to get better on this biologic. Here they are, take over.” Personally, I’m making sure that we’re dealing with psoriatic arthritis and not OA [osteoarthritis]. But tell me, John, give me an example of where you switch that particular patient?

 I would consider the following: If their skin is doing really well and the joints could use some help, I would actually consider adding a conventional DMARD [disease-modifying antirheumatic drug]. One of the interesting things that we’ve seen from the SEAM-PsA trial that was done with etanercept and methotrexate in combination or monotherapy of either one that Phil Mease, [MD,] authored, was that methotrexate is a good drug for psoriatic arthritis. We were seeing ACR [American College of Rheumatology] 20/50/70 criteria responses that are respectable and even responses for enthesitis and dactylitis and some nail changes.

I certainly would consider going back to methotrexate or even leflunomide or sulfasalazine unless there’s a lot of spondylitis involved, then that’s not going to work. But then it depends on how much articular disease and how much skin involvement was there. If there was a lot of joint disease, and the skin disease wasn’t that hard to control, and the patient is suffering a lot, it might require a change from whatever biologic is working for their skin, to a different agent, hoping that one can get control of both. It’s not an easy question, and it begs the question of how much joint disease, how much damage has occurred, how much more damage might the patient be at risk for developing?

 Very helpful. Never an easy visit, and again always letting the patient know. It’s tough when they’ve gotten success, such great success in one domain, to “switch” therapy.

Switching Therapies in PsA

 Let’s talk about psoriatic arthritis specifically during this very unique year of the COVID-19 [coronavirus disease 2019] pandemic. Specifically, your practice in general. We’ll start with Steve, the dermatology side. Could you tell me about how your practice has changed during the pandemic, whether it’s patient flow or telemedicine and office therapies, can you walk us through that?

 Yes. The clinic has changed some. For 6 weeks we shut it down except for emergencies, but now we’ve reopened. In the reception room we block off some of the chairs. My clinics don’t have quite as many patients per unit time, so that patients aren’t on top of each other. But the clinic operation is pretty much back to normal. Patients are wearing masks. We have fewer visitors. Instead of walking into a room with an entourage of 5 medical students, I’ll have, at most, 1 with me at a time. We do some teledermatology, and as a dermatologist my guess is it’s probably easier to treat patients with psoriasis by teledermatology than it is to manage the rheumatologic aspects because I can look at their skin with a good camera if they have an iPhone.

I feel comfortable doing that. I’m not doing a lot of teledermatology because it does make me more like a rheumatologist. In other words, I can see fewer patients per hour, I don’t get to do simple procedures in the office that increase the revenue. Teledermatology is not going to be popular among dermatologists, but the patients seem to like it. Another thing that changed is that I find myself not worrying about tests that are of questionable value. For example, my nurses want a TB [tuberculosis] test to be done on the patient every year if the patients are on an IL-17 [interleukin-17] or IL-23 blocker. And I’m like, “No, we don’t need that anymore.” The risk of the patient going to the laboratory probably exceeds the benefit right now, and if a patient doesn’t have an annual TB test, I don’t feel so bad about that.

: That’s a great point. It’s funny because we deal with that as well, and it’s not CDC [Centers for Disease Control and Prevention]-driven, this is largely driven obviously by the payers. CDC says check before and then check as clinically appropriate. That’s a great example, and I concur with that.

: The other thing that comes up a lot is new classes of questions from the patients about how their disease impacts their COVID-19 risk, how their treatment impacts their COVID-19 risk. Immunization issues will come up. And basically, the psoriasis at least, probably has little to no impact on COVID-19. My treatments, the biologics have little to no influence. Maybe the benefit exceeds the risk. There are so few hard data to go on. There are no controlled trials, and if there is a change in risk, maybe you’re going to find a study, if you have a large enough sample size, that finds a statistically significant risk—but a clinically meaningful risk, I don’t think there is.

: Hillary, your thoughts in your clinic about COVID-19 and its impact.

 Yes, much like Steve, my actual practice patterns have not changed. Fortunately, we have the global rheumatology database now. We have ACR[American College of Rheumatology] guidelines to fall back on because those patient questions are coming in, in my office as well. They’re concerned about safety, they’re concerned about whether they can continue biologics. But as far as the practice itself, we’ve made some pretty drastic changes. Our doors have been open the entire time. Traffic did slow at the beginning when people were panicking, and we did more telemedicine then. But then the patients came back, and we have been busier than ever because patients want their infusions, they want their joint injections, they want to be seen in person. And it’s such an intense time. I’ve seen patients where this is the only time literally they have left their house in months. Other intense issues are coming up. Patients are struggling. They’re struggling to get their activity and exercise in. I think we’re hearing a whole different aspect of their health than we used to.

As far as my office, we don’t have a waiting room anymore. Their cars are the waiting room. We had to socially distance our infusion patients, so the waiting room is a second infusion suite now, and visitors aren’t allowed in. Everybody is masked, we take their temperature in the parking lot, all that. And now that our cases are rising, unfortunately, we’re starting to encourage more telemedicine again just to decrease traffic in the office over the winter. Patients do like telemedicine, so we’ll see where that goes. Interesting times for all of us.

: Absolutely. John, Hillary mentioned the ACR recommendation that had come out…has that impacted what you do? A lot of it was largely common sense to most of us. But how has the COVID-19 pandemic affected your clinic, John, and anything about the recommendations that you want to share?

 I agree with you, a lot of it was common sense and empirically derived recommendations. We shut the office in April and May except for infusions emergencies. We did all telemedicine. In June we reopened, and then the cases started to rise in Arizona. So in July and August into September, we basically saw new patients in the office, and we did return patients by telemedicine, continued the infusion patients, and then we reopened completely in mid-September, and we’ve been going that way. But I’m afraid, like my colleagues here, that the numbers are going up again, and I’m not sure how we’re going to deal with that. We’re doing all the necessary social distancing, and the masking, and not too many people coming into the office with their families. It’s been straightforward.

I had the feeling from the very beginning that this infection should be approached like any other infection. Our patients are at higher risk for more severe infectious complications, from any infection, if their systemic rheumatic disease with a high burden of inflammation is not controlled. Therefore, continuing their medications and keeping their immune systems in better check and balance, and having control over systemic inflammation, would give them a better chance in fighting off any new infection, including COVID-19. That had been my premise, and our practice pretty much observed that way. We have not stopped anyone’s therapies. Then the guidance came out, and it reaffirmed what my own angle on this was. I was happy about that, and exercising common sense precautions makes all the difference in the world.

I agree with Hillary that patients have been shut in. I’ve been amazed at how many of my patients have been of the opinion to social distance, wear masks, and none of this nonsense that we get from vocal and vociferous groups of people about objecting to all of that and making a political statement. I’ve been very happy that almost all of my patients have demonstrated none of that. But by shutting themselves in, they’ve been putting themselves at risk. I have found myself encouraging them to get out and get some walking in. It’s absolutely important. The cognitive benefits, the cardiovascular benefits, the immunologic benefits, the exercise and getting outdoors are immensely important, and I’ve been emphasizing that to patients. A lot of them had been doing some of that. Some of them needed encouraging, but it makes all the difference in the world, and it’s our responsibility to try and support them in all aspects of their quality of life in this regard.

 I agree with you, John. I’m talking to patients about walking more than ever, just being outdoors in nature, as well as the exercise benefit. We’re dealing with the mental aspect of health more than ever during the pandemic.

: We can’t emphasize that enough. In closing, first I’d like to thank all the panelists for a robust discussion that is very informative. We reviewed a lot this morning. Before we conclude, I’d like to get some final thoughts from the panelists, any general thoughts. Dr Feldman, we’ll start with you.

 I’d refer people who have an interest in this area to our National Psoriasis Foundation. The website is 

. For people who have psoriatic disease, it’s a great way for them to learn about all their treatment options and to empower them in other ways to take good care of their health.

: Yes. I come back to the fact that this is still an under-recognized, underdiagnosed, and undertreated disease. It’s important for patients who have psoriasis and have joint pain to get evaluated by a rheumatologist. It’s a very heterogeneous disease, as we’ve covered today. This can present in so many different ways.

 I would agree with my colleagues, and I would recommend to any of the audience that if you want more detailed support, and information, and guidance on treatment, I’d refer you to the ACR/National Psoriasis Association guidelines for treating psoriatic arthritis. There are a lot of detailed recommendations there.

: I thank you all for participating, and thanks to the audience for watching this 

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Biologics and Advanced Therapies in the Management of Psoriatic Arthritis

EP 1: Overview of Psoriatic Arthritis

EP 2: Psoriatic Arthritis: Comorbidities and Quality of Life

EP 3: Early Diagnosis of Psoriasis and Psoriatic Arthritis

EP 4: Clinical Manifestations of PsA

EP 5: Diagnosis of Psoriatic Arthritis

EP 6: Goals of Therapy in Psoriasis and Psoriatic Arthritis

EP 7: Nonbiologics: Treatment of PsO and PsA

EP 8: Management of Psoriatic Arthritis With Biologics

EP 9: Approaching Treatment of Psoriatic Arthritis

EP 10: DISCOVER-1/2 Trials in PsA

EP 11: Safety and Efficacy of IL-23 Inhibitors for Treatment of PsA

EP 12: Impact of IL-23 Inhibitors on Pain and Fatigue in PsA

EP 13: Biologics in PsA: Monotherapy vs Combination Therapy

EP 14: Switching Therapies in PsA

EP 15: Managing Psoriatic Arthritis During COVID-19