 Hello, I’m Mark Lebwohl. I’m at the Icahn School of Medicine at Mount Sinai in New York, New York. I am joined today by Dr Philip Mease, from the University of Washington School of Medicine and Swedish Medical Center/Providence St Joseph Health, in Seattle, Washington, to discuss management of plaque psoriasis and the importance of a multidisciplinary approach in treating this disease state.

Welcome, everyone. Let’s begin. Phil, let’s discuss together the clinical manifestations of plaque psoriasis and psoriatic arthritis. I’ll start with plaque psoriasis, which as you know, is characterized by sharply demarcated, erythematous, scaling plaques. In fact, I teach my residents that if they can say the words 

, then that’s the diagnosis. Often patients will present it with that manifestation on just 1 area, like the glans of the penis, for example. The diagnosis is missed all the time when it’s not on the elbows and knees, not on the scalp, which are the classic locations. But when you can say those words, think of psoriasis. Tell us about the many manifestations in the joints of psoriatic arthritis.

 Mark, as you know, patients typically first have psoriasis sometimes up to 10 years before they will develop manifestations of musculoskeletal disease. In various studies, we have seen that somewhere around 30% of patients with psoriasis will ultimately develop some manifestation of psoriatic arthritis. In some settings, it seems to be less, in some, more, but that’s a reasonable figure, about a third.

Interestingly, when the patients are first presenting, it will often be with a swollen joint or what we call a dactylitic digit, where the whole digit is swollen and looks like a sausage, but when you probe the patient, it’s interesting to hear that really, that’s probably not the first manifestation. Sometimes, instead of arthritis as the first experience, they may have what we call enthesitis, where a tendon inserts in the bone, or a ligament inserts in the bone—anywhere in the body, really. It could be an Achilles tendon insertion, it could be the plantar fascia, could be around the kneecap, or it could be around the rib cage. The gristle of the rib cage in this case is the entheseal organ, where inflammation is occurring. They’ll go back and they’ll say, “I had problems with chest pain or Achilles tendinitis a year ago, 2 years ago, and it was quite stubborn and difficult to improve.”

On rare occasions, the person will have a history of back pain, which was part of the inflammatory arthritis of psoriatic arthritis. The key domains that we focus on from a musculoskeletal point of view are arthritis, tender and swollen joints; dactylitis, a sausage digit; enthesitis, wherever a tender ligament inserts in the bone and can be painful because of inflammation; and axial disease, or spinal disease. When I see a patient with psoriatic arthritis for the first time, I will tell them there is no one who is going to be just like you because no one is going to have the same mix of skin disease being mild or severe, joint disease being mild or severe, and entheseal inflammation being mild or severe. And it’s going to vary from time to time. It is like when you’re sitting in the symphony orchestra performance, and you hear, at times, the whole orchestra is profundo. We have everybody playing at once, and the audience is getting stirred out of their seats. Other times, when you can barely hear the piccolo section playing, or the cellos have a little solo going on. That will be how a person with psoriatic arthritis can perform.

 I love the analogy, and it makes me think of the piece that we’re missing, which is the nail involvement, which occurs in diseases and very commonly is a marker of psoriatic arthritis. That also has many manifestations. You can get nail bed disease, so that’s usually subungual hyperkeratosis. You can get nail matrix disease. That’s usually pinning in the nail, but you can also get salmon spots and crumbling of the nail, splinter hemorrhages, and a variety of other changes that occur, which are manifestations of nail psoriasis.

The other thing that I would say is, as you described in arthritis, there are patients who have minor plaques on the elbows or minor plaques in the scalp and some patients who carried them for years as seborrheic dermatitis, because all they have is some scalp scale. When they suddenly develop plaques on the elbows and knees, you realize that all those years, what you were calling seborrheic dermatitis is, in fact, psoriasis. By the way, I don’t consider it an error to have called it seborrheic dermatitis for all those years; it’s a very mild form of psoriasis.

Clinical Manifestations of Psoriatic Diseases 

 I am curious to hear what you say about triggers for joint disease, because triggers for skin disease are well known.

There is the withdrawal of summer sun. When we hit November—the season we’re recording this in—when we hit December or even late October, patients start to come back with an exacerbation of the psoriasis, which is related to having less sun exposure. On the other hand, guttate psoriasis can be triggered by a strep throat. Other infections contribute to the development of guttate psoriasis, and then various forms of psoriasis can be triggered by medications.

For example, the withdrawal of systemic steroids is the most common precipitating cause of pustular and erythrodermic psoriasis. Lithium can generate plaque psoriasis and pustular psoriasis. Antimalarials have been associated with erythrodermic and pustular psoriasis and just a flare of general plaque psoriasis, so there are different triggers for different forms of psoriasis. Are there triggers for psoriatic arthritis?

 Absolutely. One of the things that is interesting about the disease and makes a difference from rheumatoid arthritis, for example, is that there is more activity of the innate immune system activation initial phases. The frontline defense is warning signals saying that we’ve got an infection going on in the skin surface or an infection somewhere in the body, we’ve got an alteration in the gut microbiome that is triggering disease activity, we’ve got microtrauma to the tendon attachment, which leads to dendritic cell activation, the production of interleukin-23, the stimulation of other cells in the genetically predisposed individual. All those things can contribute through innate immune system activation.

Oftentimes the disease is either monoarticular or oligoarticular, meaning 1 or less than 5 joints are being involved initially, and sometimes, the sentinel joint, as we call it, may be a joint that has previously had damage to it. The microdamage leads to activation of the immune system.

Eventually, what happens with psoriatic arthritis is that it becomes polyarticular: More parts of the body are involved, it’s progressive in nature, the spine can get involved later on in the disease. The other thing that we see is associated manifestation. Other diseases that may be present in a genetically related fashion, including not only psoriasis and the musculoskeletal aspects but inflammatory bowel disease and uveitis are associated conditions that can become inflamed and activated along with a certain comorbidity that’s including cardiovascular disease and metabolic syndrome. There’s a whole canopy of issues that will ensue after that initial inciting event.

 The 1 thing I didn’t hear you say that I know you’ve seen and we’ve seen is that the withdrawal of systemic steroids can result in a massive flair of not just psoriasis but also psoriatic arthritis.

Triggers of Joint Disease 

 I’ll tell you what we use in the skin, but what physical, psychological, and social burdens does psoriatic disease have on patients, and how are these linked? I’m sure you’re aware of an old SF-36 study. SF-36 is a measure of the impact of physical function or psychological function of different diseases. It turns out, when you look at physical functioning, psoriasis had more impact on physical functioning than conditions like cancer and diabetes. Only congestive heart failure had a more negative impact on physical functioning and on psychological functioning, and only depression had a worse impact than psoriasis.

Again, psoriasis had a worse impact on psychological functioning than cancer, diabetes, and many other diseases that, on the face of it, we would think are more sever. Psoriatic arthritis has to be debilitating. What are the psychological, physical, and social burdens of psoriatic arthritis on patients?

 Mark, it’s all that you’ve just described and more, and I’ve seen those same SF-36 data, which rank psoriasis and psoriatic arthritis right up there at the top in terms of impairment for quality of life. When you have the double whammy of embarrassing and emotionally distressing skin lesions—especially, for example, if someone has grown up as an adolescent or in their 20s—when they’ve got this social stigma, they’re embarrassed to go to the swimming pool or to the beach. You combine that with the physical disability of painful joints, painful back, and difficulty getting about. It can lead to a severe state of depression, and it’s something we clinicians just never really address adequately, in my opinion.

We are in a bit of a hurry. We realize that if we start to probe with questions about emotional well-being that we can open up a whole can of worms in the discussion with the patient. When we really need to, and they need to share their emotional burden with us as part of the trusting process with us, with the clinician, all I can do is just exhort people who are listening to take the time to inquire, and sometimes—fortunately, rarely in my experience—you’ll pick up suicidal ideation, and 1 of the things that can happen with these 2 diseases or these 2 aspects of 1 disease is that there can be increased suicide rate. That’s something we just don’t want to see.

 I know you must face some of the same challenges we face in the management of patients, but in some cases, because of the cost of treatments, they think any treatment is bad for them.

Psoriatic Arthritis: Physical and Social Burdens

 Can you talk to us about some of the challenges you face in managing patients with psoriatic arthritis?

 The obvious 1 is what you’ve alluded to, which is patients are worried and anxious —especially during the pandemic—about taking medications that have immune-moderating or immune modulating properties. They have the word 

 in their minds when they’re using the various effective medicines, like biologics or targeted synthetic disease-modifying antirheumatic drugs, so 1 of the first things we need to address is what’s the reality behind that concern or fear. I won’t diminish that severe infections can occur, but I will also try to put in perspective that the rates are low and that the rates of other adverse effects besides infection are also very low but not nonexistent. We have to talk about them, but they are very low. When you balance that against the value of using medicines to diminish inflammations, to diminish pain, to improve function, to improve quality of life, to improve work status, and also potentially to diminish some of the downwind effects of chronic inflammation in the body, including cardiovascular disease. These are all things that we have conversations about, and we do our best, and our staff does its best in trying to find the most modest expense for the patient. That’s thinking through what’s going to be effective yet not cost a home mortgage for the patients to take, and there are many programs that the pharmaceutical companies now offer for non-Medicare patients to try to reduce the cost of co-pays and to reduce the cost of medicines. Hopefully, you can start to take that out of the discussion and focus on the seesaw of cost benefit for potential adverse effects that you’re trying to put in perspective.

 It’s interesting that when I have the conversation with patients about the adverse effects, and they all hear these ads on TV about infection and malignancy, and that really stays in their mind. I’ll point out to them that older drugs, specifically tumor necrosis factor [TNF] blockers and certainly the very old drugs, like methotrexate and cyclosporine, were unequivocally associated with infections and malignancy. They have black box warnings about infections and malignancies; new drugs don’t.

In fact, if you look at the package insert for the new drugs, the word 

 does not appear, and if you look at some of the new drugs in the oral realm, apremilast is a phosphodiesterase inhibitor; so is caffeine. The adverse effects that occur with apremilast are diarrhea and weight loss. The diarrhea is temporary and generally resolved within a couple of weeks. The weight loss, most of our patients want. And headache are usually mild to moderate and self-limited.

With the IL-17 blockers, there are people born with that IL-17, and they get yeast infections, they get chronic mucocutaneous candidiasis. They don’t get more malignancies, they don’t get more heart attacks, and all the data look like they’re not going to get more malignancies or heart attacks. For the patients on the IL-23 blockers, the closest example we have to that is people born deficient in p40, or people who have been treated for years with ustekinumab.

They get salmonella. People born deficient in p40, that’s IL-12 and IL-13, get salmonella infections, which has not been reported in patients on these drugs, and they get microbacterial infections. We’re going to get a tuberculin test once a year, and I say to patients, “We could have predicted that our patients on the latter 2 drugs would do well with COVID-19 [coronavirus disease 2019] because there’s not an increase in viral infections.

If you look at TNF blockers, the picture is not as clear, but it’s interesting. When you look at published studies that review pivotal trial data, they look at it very differently. Some of them make a mistake because you can’t count yeast infections as viral infections. Some of them make that mistake. Sure enough, when you look at registries of patients who have been infected with COVID-19, it looks as though patients on all the biologics, if anything, do better. They don’t do worse, and for methotrexate, that might not be the case, but they also might do better. That’s controversial.

Low-dose steroids at the outset are probably not great, but certainly late in the disease, steroids appear to be beneficial, so certainly, you can’t paint with 1 brush. The biologics appear to be good, not bad, in that setting, and I have managed to calm my patients down about that, and they’ve been accepting of the biologics.

Challenges in the Management of Psoriatic Arthritis

 I’m going to move on to a subject that really impacts our colleagues. How do you pick a particular drug? I always hate getting the question asking which drug is the best. Every pharmaceutical company thinks its drug is the best. Until you get a patient with a contraindication to that drug. I’ll start this question with an anecdote, and the question is, what is your approach to assess how to treat each individual patient? I had a talk to give at a National Psoriasis Foundation patient meeting. There were 107 people in the room, and I asked everyone to stand up. I said that at the end of this list of conditions I’m going to read, if you’ve had 1 of the conditions, I want you to sit down.

I started with: Do you have joint pain or psoriatic arthritis? Are you overweight? Do you have Crohn disease or ulcerative colitis? Do you have multiple sclerosis? Do you have lupus? Have you had hepatitis B or C, or do you currently have hepatitis B or C? Do you have HIV? Do you have risk factors for cardiovascular disease, like smoking, a family history of heart attacks, a personal history of heart attacks, hypertension, or diabetes? Have you ever had a malignancy of any kind? I had a couple more, like congestive heart failure. I said, “OK, if I mentioned a condition that you have, sit down.”

Of 107 people, 1 person was left standing. So I really hate when an insurance company says to me, “You have to use this drug first because they’re all the same, and this is the 1 we want to use first.” It is so contrary to what we are taught in terms of doing what’s best for a patient, so we’ve published a couple of articles that get cited a lot about which drug do you give to which patient. We go over all these comorbidities. How would you answer that question when you get asked, which drug is best?

 I don’t. In fact, I have a little resentment about the question. You hit the nail on the head, Mark. Every patient is an individual story, and every patient has certain comorbidities that need to be taken into context when we are making a choice. Every patient has a knowledge of someone in his friendship network or a relation who has been on medication before, and they may have preconceived notions, so it’s a conversation that occurs.

Our role is to lay out the data on relative efficacy and safety, mode of action, how it’s given, and cost. They’re providing us with, “Well, I’m a patient, but I’ve got this background story that is rich with all those issues that we just talked about.”

Multiple sclerosis, for example. That would be a signal to us that we shouldn’t use a tumor necrosis factor inhibitor, for example. Or if the patient is morbidly obese, we should probably avoid something that’s going to cause liver toxicity because they may have fatty liver, which is going to predispose them to other problems. We have to be holistic health practitioners to take all this in, to impart education, and then come up with a decision about if we’re going to do this now, and then if this happens, we’re going to do this and this. It’s a whole process.

 The next question I want to address is really more for me than for you. At what point in the treatment of psoriasis do I seek a rheumatologist’s help? We’ll see if a patient has any significant disease. If they have trivial disease that they hardly complain about. I might not send them to a rheumatologist, but if they have significant disease, you do things we don’t do.

I have no education about physical therapy. There are some diagnostic maneuvers that you can do that I am just not going to be good at. Injection of joints is something that dermatologists simply do not do, so if somebody has any significant degree of disease, I’m going to comanage them with a rheumatologist. I would say, certainly in my practice, that is common.

Assessing Individual Patient Needs With Plaque Psoriasis

 The next question I want to ask and answer is about the standard of care for initial therapy. Here’s where you actually have treatments that we don’t use, so why don’t we start with you. What would your standard of care be for moderate to severe psoriatic arthritis?

 Typically, when a person starts to have musculoskeletal aching and stiffness, 1 of the first things they’ll do is go to their shelf and get some ibuprofen or Aleve, which they have to treat their headache. If that’s helpful, great. They’ll use that for a bit. Eventually, if there is any degree of disease severity, they’ll bring it to the attention of a clinician, hopefully either their dermatologist, who would refer them to a rheumatologist, or their primary care doctor, who would refer them to a rheumatologist. Then we start introducing, at the base of the ladder, what we call conventional synthetic DMARDs [disease-modifying antirheumatic drugs], like methotrexate, but the care standards are gradually changing. There are certain situations where we actually might leapfrog to a biologic or target synthetic DMARDs in the new oral medications like apremilast or a JAK inhibitor.

It depends a lot on what they’ve tried already, what they have the capability of accepting at this stage when they’re being newly diagnosed, and then moving on to more significant therapies, especially with more disease.

 There’s a long list of things that dermatologists [have but don’t use]. Even though azulfidine, for example, has been studied for psoriasis, we never use it, and it did have efficacy. We never tell our patients to take NSAIDs [nonsteroidal anti-inflammatory drugs]. I will say, if someone has mild psoriatic arthritis, I can tell them to go to over-the-counter ibuprofen or naproxen and ask them to take that. The number of times a dermatologist would tell a patient to do that is incredibly small, whereas that’s part and parcel of what you do every day.

 In terms of our initial therapy, if it’s moderate to severe, they’re usually beyond creams. Then they get into the realm where we discuss phototherapy, which you don’t have, of course. I would say, generally, oral therapies nowadays, with the exception of apremilast, have too many adverse effects or don’t work well enough. We often skip those, so methotrexate is not used often by dermatologists anymore.

Cyclosporine is hardly ever used. Acitretin doesn’t work well enough and has severe mucocutaneous adverse effects, hair loss, and things like that. We don’t use it that much, although for all those drugs I just mentioned, by people who see a lot of psoriasis, like me, I do occasionally have patients on them. But for patients with moderate to severe disease, if they’re going to come 3 times a week for phototherapy, God bless them. I wouldn’t, but I understand people wanting to avoid any “medicines.” Phototherapy is quite safe, but it is a pain in the neck. It’s 3 times a week for months.

We then go to biologics, and I have some patients on apremilast. It’s modestly effective, but it’s extremely safe. Patients are willing to take that. We’ll talk more about that later. But when it comes to biologic therapies, what an insurer will pay for has some impact on us, but we do try to fight for the best treatment for that particular patient, based on the comorbidities they have. Nowadays, the majority of my patients are started on a biologic therapy.

Interestingly, coming soon we have tofacitinib, which looks like it is going to have an excellent safety profile and is fairly effective. We’ll see what the FDA does in terms of monitoring that drug and monitoring requirements. Apremilast, as you know, does not have any monitoring requirements. But the safety that we’ve seen so far in clinical trials with tofacitinib make it a really promising drug. In the future, we have other JAK inhibitors coming as well, although 1 is specifically a tyrosine kinase inhibitor that has a novel part of the molecule the tofacitinib blocks. That’s why it doesn’t give us the adverse effects of JAK1, JAK2, and JAK3 inhibition. That may have a major impact.

We go primarily to the biologics. They’re very targeted and very focused, and that’s why they’re so safe and highly effective. We’ll talk about the mechanisms of each and what the future looks like for those patients. In terms of the role of topical therapy, which I was asked about, we do combine it with systemic therapy, and I would imagine that rheumatologists do as well. If you have somebody who achieves PASI [Psoriasis Area Severity Index score] 75 or PASI 90, that’s still 10% to 25% of the body surface area that might not be cleared. You might want to treat that with a topical in addition to whatever systemic agent you’re using. Topical therapy still has a major place, and of course for mild disease, topical therapy rules. We generally use topical therapy only for mild disease. Patients with limited disease are often reluctant to accept the systemic therapy.

Standard of Care: Psoriatic Arthritis and Plaque Psoriasis

 Let me move on to the next class of therapy, which is traditional oral systemic agents like methotrexate. How often do you use that nowadays?

 We use it frequently, and this is partly because it’s inexpensive and there’s no challenge at the insurance company level. There are potential adverse-effect issues that patients just don’t like. If they have nausea, mouth sores, or hair loss, they obviously don’t like it. There are restrictions on lifestyle. We encourage them not to drink too much alcohol while using methotrexate, and there is the need for blood testing and blood canal liver function test every 3 months. The drug is useful, but it comes with a little bit of baggage.

More often these days, we’re moving rather quickly through methotrexate onto either a biologic or a targeted synthetic disease-modifying antirheumatic drugs. We may keep some methotrexate in the background, especially to reduce what we call immunogenicity with the biologics. The patient may develop an immune reaction against the biologic agent, so sometimes methotrexate can abrogate that. It’s used, but increasingly we’re relying more on the newer, more effective and potentially safer medications.

 The adverse effect that has gotten dermatologists to not use it, and I would say rheumatologists have the experience with rheumatoid arthritis because they treat lots of patients with methotrexate. Psoriasis patients, unlike rheumatoid arthritis patients, are obese, so the liver is much more sensitive. That’s why for many years, we had guidelines before we had the drugs we have today. We had guidelines that called for frequent liver biopsies, which we don’t call for anymore, but we don’t use as much methotrexate because of the hepatotoxicity that we see.

The other adverse effects, which I noticed you didn’t mention but I know you’re aware of, are actually from a rheumatology study done years ago where they looked at double-blind placebo-controlled trials of methotrexate for primarily rheumatoid arthritis. The frequency of pancytopenia or death in well-controlled trials was 1.4%. That means if you treat 200 patients, you’re likely to endanger the lives of 3 of them, and that’s what really frightens us from using methotrexate. I would say, more than the liver, it’s the bone marrow toxicity.

Interestingly, insurers used to require that patients fail methotrexate. They no longer require it. They get it. We would write a letter saying, “Look, this drug kills people. You want me to give it to the patient, but would you take it?” We hardly ever have to write that letter anymore. There’s an occasional insurance company that insists on it, but we’re usually able to get around doing that.

I will say also, in terms of standard of care, our recent joint National Psoriasis Foundation/American Academy of Dermatology guidelines discuss all the treatments but make them all options to be used and do not say that you should use 1 over another and put it really squarely in the hands of the physician: Does the patient have liver disease? Are they obese? Do they have psoriatic arthritis?

On average, patients with psoriasis are obese. That’s a relative contraindication to the use of methotrexate, so our most recent guidelines are actually superb in doing that.

Using Oral Systemic Agents for Psoriatic Arthritis Treatment

 Let’s go on next to the new nonbiologic agent, apremilast. It appears to be quite safe. It’s a phosphodiesterase inhibitor and requires 0 blood monitoring. How often do you use it in psoriatic arthritis?

 We use it in a couple of circumstances. One is for the patient who has been already on a drug like methotrexate, who is not doing well because of either effects or lack of efficacy. They’re not quite ready to move on to an injected or infused biologic medication. They’re a little nervous about adverse effects, and they love the safety profile of apremilast when they hear it.

Safety is a little different from tolerability, so there are, as you alluded to earlier, problems with potential earlier on as we use the drug: nausea, diarrhea, headache. I find that oftentimes, those symptoms go away over the first month or so, and after that, the patient is clear sailing. Then we look forward to seeing if it’s efficacious. If it is, then we don’t lose any sleep. It’s a very safe medicine, and there are 0 issues with malignancy signals and infection signals. You don’t have to do lab monitoring, so it’s a very clean drug in that regard. If it’s helpful for their arthritis and their psoriasis, then we use it in that context.

The other context is a person who has some major comorbidity that would represent a risk in taking 1 or another biologic or other targeted synthetic disease-modifying antirheumatic drugs. An example of that would be a patient who has some kind of chronic infection issue in their background, like chronic sinusitis, for example. This would be a good choice for them or for some other comorbidity, where we want a drug that has a very clean mechanism of action. Then there are occasions where the drug may be used in combination with other drugs to provide some additional benefit.

 We have almost identical remarks. We look at patients who don’t want injections, and that’s where we use it. We do use it before methotrexate. I’d say methotrexate is waning now that we have these safer drugs. The other area where I know you use it, and we do as well, is in combination for selected patients because of its safety. In combination, I get nervous about combining immunosuppressives, and I view apremilast as hardly being immunosuppressive. In fact, I don’t view it as being immunosuppressive at all.

Many years ago, when the TNF [tumor necrosis factor] blockers were primarily being used, I had a group of medical students do a review of every single case report of a malignancy or an opportunistic infection reported with biologics, and in two-thirds of the cases, it was because of combination therapy. It was usually methotrexate, steroids, or 6MP [6-mercaptopurine], so I don’t like using methotrexate with a biologic for that reason. I don’t lose any sleep over apremilast, so I actually use it in combination therapy, and more insurers are allowing it.

They are particularly allowing it if the dermatologist prescribes a biologic, the rheumatologist prescribes apremilast, or vice versa. We can get away with it, and it seems to work well. We have actually quite a few patients on combination therapy, and you probably do as well.

Treatment of Psoriatic Arthritis With Nonbiologic Agents

 Let’s talk about the other agents. What about tumor necrosis factor [TNF] blockers, and I think the American College of Radiology, in their latest guidelines, called on them being first-line therapy. Do you want to tell us about TNF blockers?

: Back in the years 1999-2000 when the first reports on TNF inhibitors were coming out, first in rheumatoid vasculitis, and then subsequently in psoriatic arthritis, it really was a sea change for us. Here we have a group of medicines that can lead to remission or low disease activity that can fundamentally change the trajectory of a patient’s life who has these diseases, so they have been very welcome workforces for us. They have adverse effect [AE] issues associated with their use, including the potential for a severe infection, rare risk or malignancy such as lymphoma, nonmelanoma skin cancer, and even rarer AEs like multiple sclerosis. The cost benefit has so much been on the side of the benefit that they have revolutionized what we do in our practices and what we can expect for our patients. When I see a patient for the first time, I’m letting them know that they’ve come along with this disease at a good time in terms of our ability to really impact it. It is very different than when I first entered rheumatology practice in 1982 when, believe it or not, our main treatment for these diseases was weekly injections of gold. We’ve moved beyond the alchemist stage, and we’re now into the stage of precisely targeting inflammatory molecules that leads to very good outcomes.

: You changed the way the world practices in psoriatic arthritis. You were the first author of that 

 article, which showed that etanercept prevented the radiographic progression of joint disease, and that is a bar to which every drug ever since has been held. Everyone has had to go after and make those claims, and some of them cannot. We’ll talk about some of them coming up, but that really changed the way we practice. It’s interesting; in recent conversations, dermatologists still want to see that it prevents the radiographic progression of joint disease, and apparently, rheumatologists pay less attention to it, is what I was told at a recent meeting with my colleagues, but you know that the ones that can make that claim are the ones that work better.

There’s no other way about it. They work better for arthritis, not necessarily for psoriasis. So we move on now to ustekinumab, which actually is superior to many of the TNF blockers for psoriasis but never got to make the claim and prevents the radiographic progression of joint disease because, although it’s approved, it doesn’t work as well. Wouldn’t you agree?

: The data would suggest that it doesn’t work quite as well as what we’ve seen with the TNF inhibitors and some of the newer agents, and so that is correct, but the safety profile is very good, and as you say, the psoriasis benefits are great. It’s very infrequent administration, but I think it has a definite place, and it can sometimes benefit, for example, if a person has coexistent inflammatory bowel disease. It can help them out, as well.

: Right, and I will say, when ustekinumab came out, we had patients on etanercept or adalimumab, for example, whose joints were fine. We didn’t even know they had psoriatic arthritis.Their psoriasis was not that well controlled. We switched them to ustekinumab; they clear completely, but had whopping arthritis, which was being suppressed by etanercept and adalimumab, and in many cases, we ended up having to switch them back because of the joints.

TNF Blockers as First-Line Therapy for Psoriatic Disease

 Let’s talk next about the interleukin [IL] 17 blockers, which I think represented a breakthrough, both in psoriasis and in psoriatic arthritis. They are so effective for the skin and rapidly effective. We see in days an improvement in the skin lesions of psoriasis, and … in psoriatic arthritis, too. I’m just going to say they’re profoundly effective. We’re now no longer talking about Psoriasis Area and Severity Index [PASI] 75, we’re talking about PASI 90 or 90% improvement in psoriasis severity scores, so what’s their impact on psoriatic arthritis [PsA]?

: They do have very quick and profound effects on the skin. When they were introduced, there was sort of a bias that … maybe the tumor necrosis factor [TNF] inhibitors might work better in the musculoskeletal domains. But what we’ve seen is that these drugs work very well in all aspects of musculoskeletal disease: arthritis, enthesitis, spine disease, and now we have 2 recent head-to-head trials between the 2 approved IL-17 inhibitors and adalimumab, the SPIRIT head-to-head trial [NCT03151551] with the ixekizumab agent and the XC trial [NCT02721966] with secukinumab, and what has been shown is that both the speed of onset of action in the musculoskeletal elements as well as the magnitude of effect is just as good. They’re very similar and clearly, the IL-17s are superior in the skin and slightly better in terms of safety, and so I think that that has helped cement the place for ixekizumab and secukinumab. We anticipate additional IL-17s coming along to have a substantial place in the management of psoriatic arthritis, along with the TNF inhibitors.

: Now, along come the IL-23 blockers, and  now we’re not talking about PASI 75 at all anymore, it’s just PASI 90, and even PASI 100 for some of them. The other advantage of them is, they’re given infrequently, every 2 or 3 months, so certainly for the skin, they are profoundly effective and are so targeted, like the IL-17s, where they appear to be extremely safe.

The IL-17s have a small drawback in that they can cause Crohn disease, it appears. The IL-23s, probably, at the end of the day, will treat Crohn disease. It’s great for the skin and great for the gut. What’s the impact on the joints?

: From the data that we’ve seen, primarily from phase 2 trials with risankizumab and tocilizumab and phase 3 trials with guselkumab, we see that the musculoskeletal effects are comparable to what we’ve seen with the IL-17 inhibitors and the TNF inhibitors. There’s a question mark around their full benefit for the spine, but interestingly, 1 of the substudies in the guselkumab program was looking at patients with radiographically defined sacroiliitis in finding that their symptoms improved as well in the spine, so we’re hoping that this new drug class for us will have the same benefit across all musculoskeletal domains as the other biologics, and clearly  have very significant impact on the skin disease and are very safe.

: In terms of radiographic progression in joint disease, guselkumab has looked at that, and if you move the dosing to every 4 weeks, the American College of Rheumatology [ACR] scores aren’t that different than every 8 weeks, but in terms of the x-rays, it looks like every 4 weeks achieves the prevention of radiographic progression of joint disease. I will say also, these are not head-to-head studies, but the difference between active and placebo in the IL-23 blockers appears to not be as great as in the TNF blockers or the IL-17 blockers. Am I putting too much weight on that?

: It’s a little early for us to tell, and we need a little bit more time. I must say that I’d like to see the phase 3 programs for risankizumab and togekizumab

 coming along, but I think that what we're going to find is that these have a good, strong place in the armament. Just to comment on that radiographic observation, the once-every-8-week dosing came close to being statistically significant, so I’m not overly worried about it. I do think that it has the capability of inhibiting radiographic progression even though it doesn’t have a formal indication for that.

: Let’s just talk a little bit about the future. We already mentioned tocravicitinib coming out for psoriasis. I believe it is being studied for psoriatic arthritis, is that right? 

: That’s right. In fact, next week, I will be presenting as a late breaker in the ACR meeting, the PsA data from a phase 2, which is very promising in all the ways that we’ve been discussing. It will clearly move into a phase 3 program, and hopefully, at some point, we will see an improvement in psoriatic arthritis.

: I would have hoped that that would be the outcome. Tofacitinib, as you know, is approved for psoriatic arthritis, and we have an occasional patient who is just not doing well with any of the biologics. We switch them to tofacitinib, and their psoriasis and their psoriatic arthritis improved. Now, you know it wasn’t approved for psoriasis, because the FDA had concerns. It was an increase in cases of herpes zoster. They were worried it was too immunosuppressive, but in fact, in practice it’s proving to be fairly safe.

We do some blood monitoring, but unlike methotrexate, you don’t lose sleep over the blood monitoring as you do for tofacitinib. Same with cyclosporine. You do lose sleep, so I think it is a pretty benign treatment that is quite effective. Of course, tocravicitinib, from what we've seen in phase 2, looks like it’s even safer, so I would hope that would be useful in the future. I always wondered, why does the package insert for tofacitinib allow its use with methotrexate but not with biologics, which we know are safer than methotrexate?

: Unlike the discussion we had earlier with apremilast, I would be a bit more cautious with a combination of Janus kinase [JAK] inhibitor with biologics only because they both have the capability of causing severe infections, and so there could be some additive effect there. I’m just generally more cautious about that particular combination recommendation, until we see a formal trial that assesses safety with a combination between a JAK inhibitor and a biologic.

: My reaction to that is methotrexate is even more immunosuppressive, and we use that with biologics all the time. I think the answer is that it just wasn’t studied, and it was studied with methotrexate, which unfortunately ended up in an increase in herpes zoster. Biologics and tofacitinib were not studied together.

: I’m hoping that eventually we end up with the ability to prescribe these together. I think they will be safer than the combination with methotrexate, and that is my gut feeling, although that, of course, is very off-label.

: For us to break through our current situation, where we do have patients failing treatments, we’re going to be pushed to doing more and more experimentation with combinations.

: Yeah, I would agree, and I think an exciting new development for both us is bimekizumab, which has just great psoriasis skin scores and psoriasis joint scores.I believe that 1 is probably due next summer, so hopefully, we’ll be seeing that eventually.

: It will be a little bit beyond that before it’s realized. We’re very excited about some of the data we’re seeing in phase 2 for psoriatic arthritis, and they’re in phase 3 trials now.

IL-17, IL-23 Blockers for Treatment of Plaque Psoriasis

 Let’s talk about the future. We already mentioned tofacitinib coming out for psoriasis. I believe it is being studied for psoriatic arthritis. Is that right?

 That’s right. In fact, I am presenting, at the American College of Radiology Annual Meeting, the psoriatic arthritis data from a phase 2 trial, which is very promising in all the ways that we’ve been discussing. It will move into a phase 3 program, and hopefully, at some point, we will see an improvement in psoriatic arthritis.

 I hope that will be the outcome. Tofacitinib, as you know, is approved for psoriatic arthritis. I will say, we have patients on occasion who do not do well with any of the biologics. When we switch them to tofacitinib—I’ll ask you a question about the use of tofacitinib with other drugs—their psoriasis and their psoriatic arthritis improved. It wasn’t approved for psoriasis because the FDA had concerns; it was an increase in cases of herpes zoster. They were worried it was too immunosuppressive, but in practice it’s proving to be fairly safe.

We do some blood monitoring, but unlike methotrexate, you don’t lose sleep over the blood monitoring you do for tofacitinib. Same with cyclosporine; you do lose sleep, so it is a pretty benign treatment that is quite effective. Tofacitinib, from what we’ve seen in the phase 2 trial, looks even safer, so I hope that will be useful in the future. I’ve always wondered, why does the package insert for tofacitinib allow its use with methotrexate but not with biologics, which we know are safer than methotrexate?

 Unlike the discussion we had earlier with apremilast, I would be a bit more cautious with a combination of JAK inhibitor and a biologic because they both have the capability of causing severe infections, so there could be some additive effect there. I’m generally more cautious about that particular combination recommendation until we see a formal trial that assesses safety with a combination between a JAK inhibitor and a biologic.

 My reaction to that is methotrexate is even more immunosuppressive, and we use that with biologics all the time. The answer is that it wasn’t studied, and it was studied with methotrexate, which unfortunately ended up with an increase in herpes zoster; biologics and tofacitinib were not studied together.

 I’m hoping that eventually we end up with the ability to prescribe these together. They will be safer than the combination with methotrexate, although that, of course, is very off-label.

 For us to break through our current situation, where we have patients failing treatments, we’re going to be pushed to do more experimentation with combinations.

 An exciting new development for both us of is bimekizumab, which has just great psoriasis skin scores and psoriasis joint scores. Would you agree?

 I believe that that 1 is probably due next summer, so hopefully we’ll be seeing that.

 It will be a little beyond that before it’s realized. We’re very excited about some of the data we’re seeing in phase 2 for psoriatic arthritis, and they’re in the midst of phase 3 trials now.

Looking Toward the Future in Plaque Psoriasis 

 Let me close with a couple of questions about a multidisciplinary approach by both rheumatologists and dermatologists. How can we help get that to optimized care? Do you do it at 1 visit? Do you do separate visits? How can gaps in care be addressed?

 My response on all this is education, education, education. There is so much lack of awareness beyond the medical dermatology and rheumatology communities about psoriasis and psoriatic arthritis and the optimum management of the conditions, as well as diagnosing the conditions. Psoriasis may be a little easier, but you could have comments about that to diagnose, because it’s there on the skin surface.

Psoriatic arthritis gets interpreted as osteoarthritis or fibromyalgia. In 1 study we did, the PREPARE study, it was found that nearly half the patients who were ultimately considered to have psoriatic arthritis were never aware that they had the disease. As new generations of medical practitioners come along, they have very little in their schooling. It’s so important to get education to nonrheumatologists and nondermatologists about identifying the diseases and triaging them to get to dermatology and rheumatology care. Once there, if you’re with practitioners who are not hesitant to pick up the phone, call your colleague down the hall or down the street to the other discipline—dermatology or rheumatology—and kibitz about optimal management. They are sharing, either by serial visits to their own offices or in with what is present in many academic centers and combined clinics, so both rheumatologists and dermatologists see the patient at the same time. The quality of care that’s coming out of this shared decision-making approach is really fantastic.

You raised a point about academic medical centers using a rheumatologist and a dermatologist together. We considered that, and in our polling patients we realized that there was going to be a problem in terms of a double bill—they were going to get billed by a rheumatologist and a dermatologist. Unfortunately, a lot of dermatologists don’t accept the Obamacare Affordable Care Act insurance plans that are out there. They have very high deductibles, they have significant co-pays, and their reimbursement rates are extremely low, so a lot of patients are paying out of pocket even if they think they have coverage. They come to an office and get to see a rheumatologist, and they get 1 bill that’s not well covered and then another bill that’s not well covered, and they object to having 2 bills. That’s why we did not do that at Mount Sinai.

We do have 2 people who are board certified in dermatology and rheumatology, but we opted not to have joint clinics in our clinic, which is largely a Medicaid population. We are actually working on having a board-certified rheumatologist and dermatologist as the person seeing them, but we’re doing it more for connective tissue diseases than we are for psoriasis. We’ll see how that evolves, and of course insurance will change if administrations change. If they stay the same, they may change insurance, and that may alter how reimbursements occur. Right now, it’s a drawback for us to have it together. As you know, there are organizations that encourage having dermatologists and rheumatologists work together. I can imagine it being a lot of fun; you learn from one another, you work together, and it is quite collegial. You’re together helping patients a lot, but the financial piece of it is problematic for us.

Optimizing Care With a Multidisciplinary Approach

 Let me ask you for last words of advice to our colleagues about how can dermatologists and rheumatologists facilitate a comprehensive approach for helping patients manage and treat the disease.

 I come back to the importance of evaluating each domain that the patient is presenting with, and not just focusing on the joints, in the case of the rheumatologist. In the case of the dermatologist, it is just on the skin. The disease is so much more than that, and it doesn’t take that much more time to quickly address the degree of enthesitis: Is there back pain? How is that doing? What’s the degree of nail disease? How severe is the psoriasis? Make sure no 1 of those domains is left behind when you’re approaching treatment. By addressing that each time, that teaches the patient to also be aware of the various domains, and they can comment to you when you’re on your virtual visits: “My back isn’t doing so well, although my joints are doing fine.” You can address each of those, and the patient is trusting that you are very comprehensive in your care. You are thinking about them, and to the extent that you can probe in a gentle manner about their emotional life, that goes a long way. It is just counseling people to be good doctors and take the time to do it. It’s extremely rewarding, especially these days when we have such a multitude of really effective medications that we can employ.

 I’ll throw in my 2 cents, which is that using a rheumatologist and a dermatologist together helps you get the right treatment for your patients in more ways than 1. When I went to medical school and I trained, I thought the best doctor was the guy who was not only dedicated to his patients, which most of us are, but who studied the most, learned the most, and knew the most.

That’s not true anymore. The best doctor is the guy who gets the best medicine and the right medicine for his patient. Sometimes, when you have a rheumatologist and dermatologist weighing in, as I alluded to earlier, you can get 2 drugs when you need them. If both of you have complained to the insurance company that they’re wrong—this is the right drug for the patient, not the 1 they’re telling me—and they hear it from 2 doctors, it helps the cause in getting the right treatment for your patient. I would use that as an advantage that many of us haven’t thought about but really is an advantage.

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Multidisciplinary Perspectives on the Management of Plaque Psoriasis

EP 1: Clinical Manifestations of Psoriatic Diseases

EP 2: Triggers of Joint Disease

EP 3: Psoriatic Arthritis: Physical and Social Burdens

EP 4: Challenges in the Management of Psoriatic Arthritis

EP 5: Assessing Individual Patient Needs With Plaque Psoriasis

EP 6: Standard of Care: Psoriatic Arthritis and Plaque Psoriasis

EP 7: Using Oral Systemic Agents for Psoriatic Arthritis Treatment

EP 8: Treatment of Psoriatic Arthritis With Nonbiologic Agents

EP 9: TNF Blockers as First-Line Therapy for Psoriatic Disease

EP 10: IL-17, IL-23 Blockers for Treatment of Plaque Psoriasis

EP 11: Looking Toward the Future in Plaque Psoriasis

EP 12: Optimizing Care With a Multidisciplinary Approach

EP 13: Approaching Treatment for Patients With Psoriatic Arthritis