® Viewpoints program titled “The Changing Treatment Landscape of Plaque Psoriasis.” I am Dr Andrew Alexis from Mount Sinai Morningside and Mount Sinai West in New York City. Our discussion today is going to focus on challenges in treating plaque psoriasis and the changing landscape of available therapeutics. Joining me in this discussion are Dr April Armstrong from the Keck School of Medicine at the University of Southern California in Los Angeles, California; Dr Andy Blauvelt from the Oregon Medical Research Center in Portland, Oregon; and Dr Erin Boh from the Tulane Medical Center in New Orleans, Louisiana.


We have a power-packed group of experts in psoriasis. It’s a pleasure to have all 3 of them here to share their thoughts and insights on the changing landscape of plaque psoriasis. To kick things off, I will turn to Dr Andy Blauvelt with my first question, which is a rather broad 1. Can you briefly review the pathogenesis of plaque psoriasis? What are the key immunologic and genetic factors that everyone should know? Go ahead, Andy.

Thank you, Andrew. Welcome to all the participants. Thanks for being here. When I describe the pathogenesis of psoriasis, I describe how it has changed over time because our understanding has increased over several decades. We used to think of psoriasis as a keratinocyte, mediated, or abnormal keratinocyte disease. That was prior to about 1980. That’s because when we look at the histology, the dominant thing we see are a thickened epidermis and activated epidermis. With the advent of the discovery of cyclosporin working in psoriasis and the advent of immunohistochemistry, we could actually immunophenotype cells within lesions.

Those things occurred in the 1980s. We realized that psoriasis was chock-full of immunocytes—white blood cells, T cells, macrophages, dendritic cells, and so forth. Our thinking evolved of it as more of an immunologic disease. Then it narrowed more to a Th1 disease when we have the Th1 vs Th2 disease paradigm that dominated the 1990s. Th1 cytokines are things like TMFL interferon gamma. The big discovery recently, though—the really important 1 for the field—is in the early 2000s a new type of T cell was described. Those were called Th17 cells, or TC17 cells, for CD8-positive T cells.

The reason they were labeled 17 is because they produced interleukin 17A as the dominant cytokine for this type of T cell. In those early years in 2000 to about 2010, psoriasis was identified as having a lot of Th17 cells, a lot of TC17 cells, and a lot of interleukin 17A being produced within skin lesions. That really was a major change because that led to new treatments being developed that target Th17 cells one way or another.

When we look at trying to target this new pathway that we think is the dominant 1 in psoriasis, we see targeting either interleukin 23 or interleukin 17. Those 2 are really closely related. IL-23 regulates proliferation and activation of Th17 cells. If we target IL-23, we see an effect downstream on Th17 cells and IL-17 production. Of course, we can target more downstream directly on IL-17, which also works wonderfully in psoriasis. That’s the overview of what we think of immunopathogenesis of psoriasis. Regarding genetics, I’d say it’s much more complicated. I don’t work in the field of psoriasis genetics, but I do keep an eye on it. We’re up to about 70 different genes that have been associated with psoriasis.

The key thing for the viewers to understand about genetics of psoriasis is that it’s not a monogenic disease. It’s not mendelian, we say, with autosomal dominant, autosomal recessive. It’s polygenic these multiple genes can play a role in susceptibility or in protection. They confer risk or protection. That’s why we don’t see psoriasis being easily tracked in families. It’s not half the children. About 10% of children of a psoriatic patient get psoriasis compared with about 2% of the general population. It is a risk factor to have a parent with psoriasis.

We do see monogenic or identical twins having concordance but not 100%. It’s about 70% of identical twins when 1 has it, and the other 1 has psoriasis. We do think of psoriasis as a genetic disease. It’s just not a classic 1 or an easily studied 1 because you have multiple genes contributing in different ways. We’re still in the early stages of fully understanding the genetics of psoriasis. We understand a lot more about the immunology now.

Thank you, Andy, for that very comprehensive answer. I like how you took it in historical context as far as our evolving understanding of this disease. That was excellent.

Role of Genetics & Pathogenesis of Plaque Psoriasis

My next question is for Dr Erin Boh. We’re going to take it down to New Orleans here. What are the clinical manifestations of plaque psoriasis? In this question, could you specifically talk about plaque psoriasis as opposed to pustular psoriasis, palmoplantar, and some of the other subtypes, Erin?

Andy, you gave me an easy question to answer. I can do that. Psoriasis is a pretty classic disease in general. Plaque stage psoriasis has locations it likes to go to. Typically, we’ll see scalp involvement. We’ll see elbows and knees involvement, but a lot of other areas can be involved with psoriasis. They are usually red and scaly, and oftentimes they’ll be very easily bleeding. They’re itchy, but they do have a nice characteristic pattern in general. We all appreciate that nice silvery scale of psoriasis. Psoriasis can also go to intertriginous areas, so not just elbows and knees.

We’ll oftentimes see it under the axilla or in the inframammary areas. Places that are considered more severe might be genital areas. We also have locations on the nails. We see characteristic pitting of the nails with psoriasis. That’s the useful hallmark to use clinically—when people have maybe psoriatic arthritis with very minimum psoriasis. You look to the nails, and you’ll often see pitting as an associated finding. In general, we lump psoriasis into that papulosquamous scaling erythematous, thick micaceous, scaling disease that we commonly see. It doesn’t often involve the face, but we do see it sometimes in severe forms where it involves the face. It may overlap with some seborrheic areas. Of course, sometimes people will see at 2 times of presentation. You’ll see maybe early in adolescence, when it’s really younger, and maybe 15 or 20 years of age.

You might get a little bit of psoriasis starting, but then it comes back again maybe in the late 50s. It’s bimodal in its presentation very commonly. That’s useful for us because, as Andy said, some people have their familial association with it. In my practice, and many people see this, kids or adolescents with psoriasis will usually have a stronger family history. They tend to have a little more recalcitrant or hard-to-treat disease over time. Over time, psoriasis does worsen for many people.

In part, it’s because of the comorbidities that are often associated with psoriasis. Comorbidities take a little time to develop. Things like insulin resistance, hyperlipidemia, maybe atherosclerotic heart disease commonly are associated with psoriasis. Maybe you say why. It would intuitively make sense if you look at the cytokine pattern. What Andy was talking about earlier. These inflammatory cytokines are upregulated in a number of immune-mediated inflammatory diseases. Psoriasis is a very good prototype of that, but those same cytokines can cause inflammation in the blood vessels.

It can cause inflammation in the liver, in the heart, so we have to think that. Over time as these comorbidities develop and become more problematic, they can cause more of the psoriasis to flare. It contributes to that overall general systemic inflammation that we associate with psoriasis.

Terrific. I’m also happy that you not only did answer that so comprehensively but also touched on comorbidities. Thank you, Dr Boh.

Plaque Psoriasis: Clinical Presentation & Impact on Patients

We’re going to shift gears. We’ve set the stage for pathogenesis and clinical presentation. Now let’s talk about treatment. We’re going to go back to the West Coast, and we’ll turn to Dr April Armstrong. April, could you take a moment and bring us up to speed: What is the standard of care for initial therapy for plaque psoriasis in 2020?

Yeah. Thank you for that question, Dr Alexis, when we think about standards of care for plaque psoriasis, 1 of the key things we think about is body surface area of involvement or severity of psoriasis. In general, when we think about those with mild psoriasis—those with psoriasis less than 5%, for example—we really think about topical therapies or target phototherapy. For those with more moderate to severe psoriasis, those patients with more extensive body surface area involvement, now we’re thinking about systemic therapy, which include biologics as well as oral therapies.

In addition to that, phototherapy. One thing to note is that, for example, you may have patients who have psoriasis involving critical areas, such as the face or palms and soles. If they have genital psoriasis that’s not well controlled with topicals, then for those patients, we may also consider systemic therapies. Traditionally, we have—I would say, for the last decade—the old paradigm going from phototherapy to oral systemic therapy to biologics. In the last 3 to 5 years, that paradigm has really shifted in terms of thinking about biologics, oral therapies, and phototherapies concurrently. In fact, these days, 1 of the key recommendations that has been put forth is that for most patients, we do want to consider biologics as 1 of the first-line treatments for patients with moderate to severe plaque psoriasis. One thing to also note is that the presence of psoriatic arthritis really drives our selection of therapies as well.

If a patient has psoriasis but also psoriatic arthritis, then we really want to think about systemic treatments that can target both psoriasis and psoriatic arthritis. When we think about our psoriasis therapies, we have TNF [tumor necrosis factor] inhibitors, which are etanercept, adalimumab, certolizumab, and infliximab. They are FDA approved for both psoriasis and psoriatic arthritis, which Dr Blauvelt will talk about in more detail a little later. Then IL-17 inhibitors, which as a class came on after the TNF inhibitors, including secukinumab, ixekizumab, and brodalumab.

The 2 of them, secukinumab and ixekizumab, are approved for psoriasis and PSA [psoriatic arthritis]. Brodalumab, while approved for psoriasis in the United States, is also approved for psoriatic arthritis in other parts of the world. Following that class is IL-23 inhibitors, which include guselkumab, tildrakizumab, and risankizumab. They’re really known for their infrequent dosing and robust efficacy in psoriasis. Recently 1 of the IL-23 inhibitors, guselkumab, also gained approval for psoriatic arthritis.

Thank you, April. Excellent overview, and it really sets the stage for the rest of our conversation today.

Plaque Psoriasis: Current Standard of Care

We’re going to go back to Dr Blauvelt. Now that we’ve got this overview of the various biologics available and the evolving paradigms as far as initiation of therapy, could you kindly discuss your experience with what we’ll call the first wave of biologics starting with TNF [tumor necrosis factor] inhibitors, subsequently the IL-12/23 inhibitor class, and IL-17 antagonists?

Sure, Andrew. Thank you for asking me that question. I feel like I’ve ridden the wave of all these over time. I was involved in the approval of efalizumab, which was the second biologic drug for psoriasis, in 2003. The first TNF came out in the spring of 2004 for psoriasis, and that’s etanercept. As soon as it was approved, I started using it. We all thought it was this incredible drug. I was chief of the VA at that time, and I had to get this new drug on the formulary at the VA. That was my big thing.

We used it right away, and we thought it was wonderful. Compared with some of those older things that April talked about—topicals, phototherapy, methotrexate, acitretin—most of us thought etanercept was a big move forward. Then we had infliximab in 2006 and adalimumab in 2008. I’d say both drugs had higher efficacy, in my experience. I moved to those drugs, I would say quickly, from infliximab to adalimumab, because it was subcutaneous, whereas infliximab was IV [intravenous]. In my experience, I was using them a lot when they first came out, with good success, thinking they were great.

The next drug approved was in 2009, and that was ustekinumab, an IL-12/23 blocker. I thought that was much better. Look at the efficacy at that time, and the efficacy looked better than all the TNFs except perhaps infliximab. It seemed safer to me, and that was my experience as I started to use ustekinumab. For many years, that was my go-to drug because we didn’t have the next biologic approved until 2015. For those 6 years, I’d been evolving and using the latest and greatest. I’d been quickly adapting and quickly accepting them as time went on.

With ustekinumab, everyone seemed to love the infrequent dosing, the lack of major adverse effects that we would see in some of them with the TNF class, but we didn’t always. I guess the problem, in my experience, with ustekinumab over that time period was that not everybody could go 12 weeks. A lot of folks ended up breaking through around the 8-week, 10-week time point. Sometimes I could get them to every-8-week dosing and sometimes I couldn’t. There was some deficit there in that armamentarium or with that drug. The other thing developed over that time is it seemed to be better for skin efficacy compared with TNFs but not as good for psoriatic arthritis. As April mentioned, that has always been in my mind—for patients who have both conditions—influencing my choice.

There was still some need there, some hope for something better that would have the skin efficacy, but maybe some better joint efficacy, but a lot of the infrequent dosing. Then along came the IL-17 blockers. As April mentioned, that’s secukinumab, ixekizumab, and brodalumab. As a general rule of thumb, the efficacy was higher in that class of drugs compared with ustekinumab and the TNF blocker class. They were receiving even greater levels of skin clearance, both in the clinical trials and in the clinical practice. We saw them working better, in my practice and in my trials, on joint disease than ustekinumab.

It filled some of the niches that we were looking for in ustekinumab. But on the other hand, the dosing was more frequent. They’re either every 2 weeks for brodalumab or every 4 weeks with ixekizumab and secukinumab. To describe my experiences, I’ve been riding the wave and really loving the evolution. Going from class to class and trying, in my mind, to pick the best 1 for my patients. I hate step therapy.

I know we haven’t talked about that yet, but a lot of times that has also been my experience, battling insurance companies—you have to use this, this, this. I agree with April. Over the last several years, it’s been much better not having to go through what Craig Leonardi calls the ladder of shame, where we go through all the older, less effective, and less safe drugs before we get to the good stuff. I really don’t like doing that. Whenever an insurance company will allow me to, I avoid that step therapy and just go with what I think are the best drugs for my patient.

Great. Thank you for taking us along that winding road of evolving therapies and discussing some of the pros and cons.

Biologic Therapies for Plaque Psoriasis

Let's shift over to safety. Just as important as efficacy is safety. Dr Boh, what are the adverse effects? What are some of the adverse effects that we should be mindful of when thinking about the various classes that Dr Blauvelt covered, specifically TNF inhibitors, the IL-12/23 inhibitor class, and the IL-17 inhibitors? What are the key adverse events we should know about?

Well, I think there are not as many as we had with our systemic therapies. Just to set everything in perspective, as a group, the biologics are very safe. They have a good safety profile. If we look at the first generation of biologics, which I like to call the TNFs, because those are the ones that we really have a lot of data on, there are some adverse effects, and they're not going to be for everyone. In general, the adverse effects are few, but what we have to think about is patient selection. If you take the TNFs, people who have morbid obesity, that may be an issue with the TNFs, because most of them are not weight based, except the infliximab, and most dermatologists don't use infliximab. I love it. It's great for patients who are obese. The other thing that can happen with the TNFs is some people will have a paradoxical weight gain. In general, if you're on the TNFs, you have to be careful if you have severe congestive heart failure [CHF]. You'd have to be careful in terms of the risk, very low, of inducing or unmasking a multiple sclerosis [MS]. People with first degree relatives with MS, I steer away from the TNFs. You want to remember that the TNFs as a group can degranulate.

As a consequence, you can reactivate old TB [tuberculosis]. You can also reactivate hepatitis B. They're going to require screening, and a little bit more blood work with them. The TNFs, as a group, can increase or induce elevations in your liver tests. You have to be a little bit careful about that. Those are not very common, but they are ones that we want to watch for. There is a very slight increased risk of malignancy, especially maybe squamous cell carcinoma, with the TNFs. But again, not too bad, but theseare things we need to monitor more than the third generation of biologics.

If you look at ustekinumab or the IL-12/23s, they do have a very good safety profile. The adverse effects that I can come up with for ustekinumab are a couple. One, some people can't go the whole time. They can't control going 12 weeks. The majority can, but some will break through. It's not as good for joints as our TNFs, which are first line for prominent psoriatic arthritis. There are some people for whom it just doesn't respond. Ustekinumab's safety profile is very good. There was initially some ruckus about maybe inducing a little bit higher incidence of MACE [major adverse cardiovascular events], especially with these drugs. That hasn't played out in the long run.

If you take the second or third generation of biologics, the IL-17s, they're even safer and have fewer adverse events as opposed to the TNFs. As you go closer to the pathogenic bullet in psoriasis, I think many of the adverse effects get less. With the IL-17s, what do we need to watch for? We certainly have a slight increased risk of yeast infections, candida infections. The big thing with the IL-17s, of course, is going to be inflammatory bowel disease. You want to take a careful history because you could unmask it, or you could induce it even. That's a very low risk.

Simple questions and screening would help mitigate that, but you do have to be careful because it can unmask or induce an inflammatory bowel-like process. That's something that you do want to be careful about. There is a black box warning, of course, on one of the drugs, brodalumab, in terms of increased risk of depression. In general, I don't worry about that too much. Patients with psoriasis generally are more depressed than other people anyway. I don't think that brodalumab is going to make it that much worse. But again, all patients need to be screened for depression who have psoriasis.

We do follow our patients on brodalumab a little bit closer to make sure that they don't have that adverse effect, but other than that, as a group, they're very safe. We just look at what we have to monitor, and that tells us the potential adverse events that we would see with the drugs.

All right. Thank you. Now, Dr Armstrong, just briefly, I know Dr Boh has pretty much mentioned all the major adverse events we need to know, but any specific contraindications, no-fly zones, for each of the classes that we've discussed so far? April?

Yes. First of all, for all of the classes, they have in their label, hypersensitivity as a contraindication. That's probably as expected. One consideration that's common to all of the different classes are things like injection site reactions, nasal pharyngitis, and upper respiratory tract infections, which can be seen with the biologics in some with an increased risk compared to the placebo. With TNF inhibitors, we want to make sure that we avoid those in patients with demyelinating diseases such as MS, patients with advanced CHF.

I thought Dr Boh did a wonderful job summarizing some of the key safety considerations regarding the IL-17 inhibitors. There are low rates of oral candidiasis that most dermatologists are comfortable treating, and typically it's not a reason for discontinuation. In the IL-23 class, overall as a class, there are not any discernible safety signals other than the contraindication that applies to all biologics of hypersensitivity.

Biologic Therapies for Plaque Psoriasis: Safety

 Moving to a different class of biologics, the IL-23 inhibitors, the ones that are p19 subunit-specific. I'm going to turn to Dr Blauvelt for this one. Could you speak to this class of inhibitors, IL-23 specific inhibitors? How are they administered? What frequency? Talk about some of the pros and cons. Go ahead, Andy.

Right. Thank you, Andrew. I see the newest class of biologics as a variant on a theme or an improvement, if you will, on ustekinumab, which is an IL-12/23 blocker. The difference in these 2 types of drugs is the type of molecule that's bound by the antibody. With ustekinumab, we're targeting p40, which is a subunit of both IL-12 and IL-23. That's why we hit both of those cytokines with ustekinumab. With the newer drugs, as you mentioned Andrew, we target p19, which is a subunit that binds with p40 to create IL-23, and it's not a part of IL-12. By binding p19, we're selectively targeting IL-23.

What we see is the same kind of infrequent dosing with these new IL-23 blockers as we saw with ustekinumab, for the most part. Two of them, tildrakizumab and risankizumab, are dosed every 12 weeks, just like ustekinumab. The third, guselkumab, is dosed every 8 weeks instead of every 12 weeks. In general, I see them as more long-acting drugs, definitely compared to the other classes.

Great. That was very helpful. What about safety? In particular, long-term safety data for this class of drugs. April, would you like to take that one?

Yes, Andrew. I would say that, overall, when we look at the safety data for the available agents over time, we do not see an increase in the numbers of adverse events, for example, that we see in the initial parts of the trials. Overall long-term data for most of the biologics that we have is really, no news is good news. With regard to TNF inhibitors, in terms of long-term safety data, what we saw is that there's no increased risk of serious infections or internal malignancy.

There are some data showing perhaps there are increased rates of SCC [squamous cell carcinoma] with some TNF inhibitors, but one thing we need to bear in mind is that a lot of these patients who were enrolled initially in these trials were also patients who had received PUVA [psoralen and ultraviolet A] therapy. Some of the previous treatment with PUVA may have confounded some of the findings that we see. Then for IL-17 inhibitors, long-term safety data look very good. There's no increased risk in terms of serious infections or malignancies. Same for the IL-23 inhibitors.

As we follow these biologics over time, consistently what we've seen is that what we saw initially, in terms of what we understood as their safety profile, we do not see increases in rates in these medications as patients are on them for a longer period, which is reassuring.

It’s very reassuring indeed, and very relevant given that psoriasis is a chronic, long-term condition. Thank you for that.

IL-23 Inhibitors for Plaque Psoriasis Treatment

Let's shift gears to a more practical question, which I'm sure is a burning question in the minds of many in the audience. That is, well, we've got all of these great choices, how do you decide on which biologic to start with? I know that's a loaded question. I want to start with Dr Boh. How do you decide? What goes into your decision? What are the factors?

Well, I'll tell you prefaced by saying that my state, Louisiana, does do step therapy. It does block a lot of things. A get-around is many of the drug companies give us drugs and they have good assistance programs. Patients can get drugs. If I'm able, I like to start with a biologic because I think safety-wise they're much better. Ease of administration, as Andy pointed out, it's easy to get a shot every 3 months. There's very little laboratory monitoring.

If I can get a biologic, I like to do that. How I choose which biologic is the key. The key to that for me is, what is the baggage? Meaning, what are the patient's comorbidities? All of these drugs are great, but it's not a one-stop for everybody, because every patient's psoriasis, even though psoriasis is classic and it looks like this, they're all different because they have different comorbidities. Patients who have arthritis and psoriasis, I may lean toward the TNFs, patients who have other comorbidities, maybe atherosclerotic disease or heart disease, again, I want to look at that and I make my choices more based on comorbidities. I also make selections based on what's easiest for the patient.

Some patients don't like needles. Other people don't want to take pills. Other people want to do their own shots. It's a conversation that I have with the patient. “What do you want to do?” I just direct them. If I have to, I oftentimes go to systemic therapies for a very short period because I can't get some of the biologics until patients have done methotrexate. I write them a prescription, they come back in a month, and I say, “Oh, you're not better, let's go to a biologic.” Then I've jumped through that hurdle. I can sometimes fight for the drugs.

Sometimes I do when people really need it. I think that's the key, you talking to the patient, and you and the patient deciding what's going to be best given the other diseases that are part of his or her package with the psoriasis. I think coverage is also important. Some insurance companies tell me, you must do an anti-TNF first. Well, I can bang my head against the wall and argue, but if they say I have to do a TNF and a TNF would fit, maybe I do that for a short time and say, “It doesn't work, or it works great but patients don't want to do it.” It's really what the patient and I come up with that is the best and safest for that individual.

Yes. Shared decision-making is very much an important aspect to this, too.

Biologic Therapies for Plaque Psoriasis: Treatment Selection

Now, Dr Blauvelt, Dr Boh touched on comorbidities. I'm curious to hear, in your practice, how do comorbidities factor into your decision for treatment. If you'd like to speak to the AAD [American Academy of Dermatology] and National Psoriasis Foundation guidelines with respect to comorbidities and how they may influence choice of treatment, please go ahead.

Sure. The first thing I wanted to talk about is to highlight that I'm not stuck on a BSA [body surface area] of 10% or more. I tend to practice going to a biologic based upon body surface area, yes, presence or absence of psoriatic arthritis, whether the disease is in special areas, like genital psoriasis or palm and sole psoriasis, and whether they have failed topical therapy. It's a little bit broader use of biologics compared to just strictly the BSA criteria. 

I find that I can get a drug for most of my patients that meets one of those criteria: failure of a topical, BSA greater than 10%, or special area involved. That fits with some new recommendations that the International Psoriasis Council has put forth as far as treating patients. Comorbidities absolutely influence my choice. The big one, the most common one is psoriatic arthritis [PsA]. In my practice, 40% to 50% of patients have psoriatic arthritis. It's higher than the often quoted 25% to 33% or so. It's a really common thing that I see. I have a broad definition of PsA.

It's really not a great term, psoriatic arthritis, because we know that morning stiffness is part of psoriatic arthritis. We know that enthesitis and dactylitis are part of psoriatic arthritis. We know that fatigue is part of psoriatic arthritis. If patients are having any of those things, I call that PsA just because we really don't have a great term for prominent morning stiffness without joint inflammation. Basically, I think it is psoriatic arthritis. For patients with that comorbidity, my class of choice is actually IL-17 blockers, so a little bit different than what Erin just mentioned.

I consider TNF blockers as the second line for my patients with PsA. I say that because the data are comparable in joint data with TNFs and IL-17s. Yet, then we also see the skin data being better for IL-17s and the safety profile being better. When I take all of these things together, that's the class I would say is my class of choice for a patient with psoriatic arthritis. The other major comorbidity for me is heart disease. It's common with more severe psoriasis and less common with more mild disease. Anybody over 10% body surface area is going to be at risk for heart disease.

We know that through lots of studies over a long time. Here, I don't necessarily go with class, I try to think about clearing psoriasis to zero because if somebody has a lot of body surface area, I want to get them lower, to lower their risk for heart disease. The best lowest mark would be zero. I'm looking at highly effective treatments, the best IL-17 blocker, the best IL-23 blocker, are kind of where I'm at for trying to get people to complete clearance for that type of patient. Obesity is another really common one that plays into things.

I'm not going to use a TNF blocker for patients who are obese. I think the data are really good as far as their efficacy not being good in the obese population. We see better efficacy data for the newer biologics. Again, probably an IL-17 or IL-23 for me for the patient who is obese. Some comorbidities are not going to change my view with biologic therapy. Things like hypertension, diabetes, other aspects of metabolic syndrome, are not going to change much.

They don't really factor too much for me in biologic choice. Obviously, the psychiatric comorbidities, depression and anxiety, which I do agree with what Erin said earlier, are really common in our population. We often, though, will see when patients are clearing their skin, improvements in the depression scores, improvements in quality of life. So again, I'm thinking of highly effective drugs. At the end of the day, I'm in this IL-23 blocker, IL-17 blocker grouping. I like to use the newer ones. I'm not using many TNF blockers at all now. It's pretty rare for me to use a TNF blocker. I'd say I favor IL-17 blockers if the patients have psoriatic arthritis. I favor an IL-23 blocker if the patients don't have psoriatic arthritis. That’s where I am now.

I'm going to turn it over to Dr April Armstrong. April, I'm going to ask for abrief comment on a practical question, which is, what goes into your decision to change therapy? You've got a patient on follow-up; they've already been on a biologic, and you're assessing them. What decisions go into switching from one biologic to another?

I would say Andrew, as Erin and Andy already said, choosing the best biologic that's fitting for the patient is the first important thing. Then what happens for me, is looking at the patient to see if they have responded to the biologic is really important. It's very important for me as well to try to treat the patient to clear, if possible. In general, I would say, if the patient is not responding after 6 months, and I wait at least 6 months, some say they wait 3 months, but I typically wait at least 6 months.

The reason is that some are just late bloomers in terms of response. I would then switch them within the class if there are comorbidities that drive my decision-making process. For example, if they have active PsA and they had been on an IL-17 before, and I think switching to another IL-17 would address not only their psoriasis, but also their PsA well. With regard to switching patients from one biologic to another class, I would say that that is definitely one of the key options I think about. Especially when someone is a primary failure on the biologic, meaning that if they have never responded well in the first place, then I think that the immunologic pathway that drives their psoriasis may be very different from the therapy that I'm trying to target. In those cases, if it's not going to affect their treatment of their other comorbidities, then I would consider switching them to a different class.

Biologic Treatment for Plaque Psoriasis: Switching Therapy 

In the remaining few minutes of our discussion, I’d like to focus on treatment challenges and unmet needs. Let me open this part of the conversation with a question. What are some of the key challenges you face when managing plaque psoriasis? I’ll start with Dr Boh.

One is access, or certainly affordability. What I find is that insurance companies, especially if you look at them, tend to deny a lot of coverage. Access and having it affordable for patients is also important. One of my biggest unmet needs—I guess it’s not my need but psoriasis patients’ needs—is I have a huge group of people who are now turning 65 years old. The Medicare population just gets terribly put to the side. You could be on a biologic from your commercial insurer for 15 years and doing great, then you turn 65 and you can’t get anything.

It’s very frustrating. The frustration is made even worse because these Medicare plans will approve the psoriasis drugs, but it’s tier 5. That means your co-pay is $2000, $5000 a month, and you’re on Medicare. Then you have these patients who had been enjoying the benefit of the IL-17s, IL-23s, or whatever they’re on, improving their health, and they can no longer get the drug. The only drugs we can get are infliximab or the tildrakizumab if you go through the Medicare major medical. The Medicare population is a big group of people we need to access the medicine for.

When they get approved, the companies can’t give them the medicine because they’re approved; they just can’t make the co-pay. That’s 1 big group. I used to say another group of unmet needs was pediatrics, but that’s really blossoming now, and we’re seeing a number of drugs entering into the pediatric population for psoriasis. There are the TNFs [tumor necrosis factor inhibitors], there’s ustekinumab. There are a number of different classes that are going down to at least age 12. Of course, with the TNFs, it’s down to age 4. That population is going to even see more benefit from these biologics in the future as we see the better safety profiles with them as opposed to traditional agents.

Summing it up, the biggest things are the cost of the drugs and access once you hit a certain age. One of my frustrations is that patients go, “I’m clear on my medicine, so I’m just going to stop it because I’m cured.” You’re going, “No, you’re not.” Then they come back 5 or 6 months later covered with their psoriasis, and you’ve got to start the whole process over. That’s a good problem to have because most patients do respond.

Thank you, Erin. You touched on the challenges of cost and access, as well as longer-term adherence. Let me open it up to everyone. If you could briefly comment on what you think our role is as dermatologists and other health care providers who prescribe biologics. What’s our role in facilitating access for our patients given that we have these barriers that we just talked about? What do you do in your office to facilitate this process?

You fight, fight, fight with the insurance company.

I think—and you just have to be persistent.

Oftentimes they will keep denying, and you just really have to have a bone in the game. Tell your patients that you are persistent on that. Andrew, if I may, I had 3 quick points on what I thought is the unmet need. One is, I see a lot of my patients who respond really well in the beginning, but then over time, they start to lose response. If we can advance as a field—in terms of research, understanding the predictability of who would do what in the future—it would be great.

Also, the long-term implications of treating our pediatric patients. I’m not necessarily saying the safety concerns, but just understanding. Are we doing any disease modification in this patient population by treating them earlier? There’s a lot to learn about that. One of the biggest battles that I find myself fighting—maybe it’s because I’m in Southern California—is just the social media information to our patients regarding therapies who really don’t work, that they are really latching onto them. In the process, they’re really losing time that they could be having in terms of going to proved therapies that have been FDA approved. That’s 1 unmet need as dermatologists that we want to take an active role in, in terms of educating our patients with regard to evidence-based medicine.

I want to highlight some of the things that April just said. If we look purely at the numbers of people with psoriasis and then cut that to the people who have moderate to severe psoriasis and then cut that to the people who are on biologic therapy, it’s a woefully low percentage of patients who need biologics are on them in this country. A lot of that has been because of misinformation on the internet, as April mentioned, and reticence by dermatologists who don’t want to take the effort and the time to fill out prior authorizations or to learn about a new biologic.

That’s an area for our specialty that has been a sore spot. I always say to folks wanting to do it or looking at doing it, just put the patient first, just think about that human being in front of you. If it was your brother or your mother, would you want them to go on methotrexate? Would you want them to go in the light box in 2020 knowing all the wonderful things we have that are so much better than those 20th-century therapies, which unfortunately are still being used by so many dermatologists because that’s how they were trained and they don’t want to deal with prior authorization. It’s not patient centered.

I’m not admonishing. I’m just trying to get people to think about putting yourself in the shoes of that person in front of you. What would you want? You would want the best therapies. We’ve got terrific ones now. I really think more dermatologists should be prescribing biologics.

Andy, if I could mention 1 unmet need. If we could get this, it would be so helpful for all patients: going down that road of personalized medicine. If we could find the individual’s genetic defect. Andy mentioned very early in the talk that we have 2000 gene mosaicisms in psoriasis. But not every psoriasis patient has the same defect. If we could find that genetic expression that’s driving that person’s psoriasis, then you pick the drug, and it would be so cost effective.

You wouldn’t have to go through this step therapy. You wouldn’t have to have people getting unnecessary treatments or not responding and getting those frustrations. You find what the defect or the mutation is in that patient and then target that defect. Then you’ll get a home run every time.

Yeah, that really is the holy grail, isn’t it?

Biologic Therapies for Plaque Psoriasis: Treatment Limitations

How do you anticipate the treatment landscape evolving? Why don’t I ask April Armstrong to start that discussion? In broad strokes, how is our approach going to evolve?

In broad strokes, I would say that in the psoriasis treatment landscape, we are going to look for agents that even have a higher efficacy, not only in the skin but also in the joint. Especially in the joint. In psoriatic arthritis, we still have a long way to go. We still use ACR20 as our bar. That aspect of psoriatic disease will just need to be addressed a little better with newer therapies.

We will also see that newer agents, with regard to topicals or oral therapies, are really looking at different classes of topical and oral therapies that work very differently from traditional therapies we have had. Therefore, addressing the need for patients who prefer oral therapies or patients who have limited psoriasis and would want to have safe and effective topical therapies.

Excellent. Briefly, Andy, what are some of the most anticipated developments in your mind that you think the audience should know about? The most anticipated developments in the field of treating plaque psoriasis.

Yeah. We do have more biologics on the way, but they’re of similar classes. We have a new IL-17 blocker that’s likely to be approved next year. We have a new IL-23 blocker that will be coming soon thereafter. But as far as something new, those will offer some incremental increases from where we’re at now. We have a new oral therapy likely to be approved in the next several years that blocks a molecule called TYK2. There, it will go to the head of the class, in terms of oral therapy for psoriasis.

It’s not going to be close to the best biologic therapy, but for those looking for oral therapies, it’s going to go to the head of the class, ahead of apremilast, ahead of methotrexate, ahead of cyclosporin, and acitretin. That’s something to look forward to. That will be really different. Then just 1 more comment. I’m involved in the scientific advisory committee for the National Psoriasis Foundation. They have a program that is Milestones to a Cure. We’re going to be using the C word more in the next 5 to 10 years, with strategies to look at cure, because we’ve gotten such great and effective therapies that we’ve spoken about, but they all require continued use. We’re going to start looking at strategies in the next 5 to 10 years that are more about knocking down disease permanently. That’s really the exciting thing if you’re going to be around for another 10 years.

Treating Plaque Psoriasis: What’s Next?

The time just flew by. We’re approaching the end of our segment. I’d like to give everybody a chance to share some final thoughts and quick takeaways about any advice you have for community dermatologists, early career dermatologists, or just the general dermatologic community about treating plaque psoriasis. Why don’t we start with Erin Boh?

The 1 word I could say is treat. If you’re a community dermatologist and you’ve got patients, you can send them to the experts. That’s great, but you ought to just start doing it yourself. People do things in their office, and they’re as risky as these. These are so easy to do that dermatologists should be doing them. Make it easy.

Figure a way that will get your office to work for you. Get your prior authorizations. Once you have a patient who you’ve given this medicine to, and they come in and say, “This happened to me the other day,” with 55% body surface area, I put her on 1 of the IL-23s. And 4 weeks later she’s coming in. She brings her husband and she brings her kids because she is so happy. Her exact words are, “You changed my life.” We can all do it. I think we just need to do it. Don’t be afraid.

I love what Erin said. I want to echo that. The other thing I wanted to say is just get yourself continually educated. Keep learning, because there are a lot of new things, but don’t be afraid to learn them. Sometimes it seems overwhelming and can be a little confusing, but hopefully educational sessions such as this will lend some clarity to our treatment paradigm.

My father had severe psoriasis, so I take this very seriously. He lived through phototherapy, acitretin, cyclosporine, and methotrexate. Unfortunately, he passed away from complications from heart attacks and strokes. He had severe psoriasis most of his life. I firmly believe it contributed to his heart disease. It’s such an opportunity, as Erin mentioned, for us to not only make the patients’ lives turn around in the present time but to make them live longer—to have an impact.

The data are emerging on heart disease and improving heart disease. I really believe that’s where the data are looking and going toward. It’s not just a skin problem. Right? It’s not just a quality-of-life issue. It is an important disease. I think about it as saving lives.

Well said. I just want to take a moment to thank our panelists. What a wonderful group of experts. Thank you for being so generous in sharing your insights and your pearls. I probably speak for many that we could probably talk for another hour and learn so much more from you. Thank you so much, but our time has come to a close. This has really been an excellent discussion. We hope you found the information to be valuable to your clinical practice. Thank you all for taking time to watch this 

The Changing Treatment Landscape of Plaque Psoriasis

EP 1: Role of Genetics & Pathogenesis of Plaque Psoriasis

EP 2: Plaque Psoriasis: Clinical Presentation & Impact on Patients

EP 3: Plaque Psoriasis: Current Standard of Care

EP 4: Biologic Therapies for Plaque Psoriasis

EP 5: Biologic Therapies for Plaque Psoriasis: Safety

EP 7: IL-23 Inhibitors for Plaque Psoriasis Treatment

EP 8: Biologic Therapies for Plaque Psoriasis: Treatment Selection

EP 9: Biologic Treatment for Plaque Psoriasis: Switching Therapy

EP 10: Biologic Therapies for Plaque Psoriasis: Treatment Limitations

EP 11: Treating Plaque Psoriasis: What’s Next?

EP 13: Managing Plaque Psoriasis: Expert Advice