Conversations in Plaque Psoriasis

The psoriasis drug landscape and pipeline are diverse and consist of both oral and injectable therapies that target a wide variety of pathways. 

In an interview with MD /alert, Andrew Blauvelt, MD, director of the Oregon Medical Research Center, spoke about the future of mirikizumab for psoriasis, as well as other options coming down the pipeline.  

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What’s next for mirikizumab? 

We've now had the two major phase 3 studies published. This is the second one. And it shows it's an excellent drug. I believe and it's now public that Eli Lilly has taken a stance that they will not go forward actually for approval for mirikizumab, in moderate-to-severe plaque psoriasis. What they have decided to do is go forward in inflammatory bowel disease. We know that other IL-23 blockers as well kind of work in inflammatory bowel disease; it's another condition where they work well. The company is pursuing approval of this drug for IBD patients but not for psoriasis patients.  

Perhaps because there's already three IL-23 blockers on the market. This would be comparable efficacy to the other three, it would not be over and above what we see with for example guselkumab or with risankizumab. We see numbers here that are comparable to those two drugs. So, it didn't beat the other IL-23 blockers, it was comparable. The other reason possibly is that the company has a major IL-17 blocker on the market, ixekizumab, and perhaps they didn't want to compete with their own drug ixekizumab by having now an IL 23 blocker, mirikizumab. 

There's always, for me, a need for new drugs on the market. Not everybody responds to everything. There's great choices now. IL-23 blockers are great, in my opinion; it's a terrific class of drugs. We have solid evidence now that this drug is terrific. It would have been a nice addition in my mind, and so I was a little disappointed as well. 

What does the treatment landscape look like currently for psoriasis? 

I'm a big advocate of IL-17 and IL-23 blockers for the treatment of moderate-to-severe plaque psoriasis. It's based upon data. It's based upon efficacy and safety data. If you look at the combination of efficacy and safety, those two classes of drugs clearly are better than TNF blockers. They're clearly better than any oral option for psoriasis. If we talk just terms of efficacy and safety, which to me are the most important features of drugs, IL-17 or 23 blockers—my message to private practitioners, if you haven't yet gone into biologics after 20 years for psoriasis, or if you're stuck on TNF blockers, please go over into 17 or 23 blockers. They're much better for patients and much safer for patients. Great efficacy, great safety, great convenience.  

Now, what's in the future? Of those two classes, the highest performers, if you will, that we have right now would be risankizumab and guselkumab in the IL-23 space and then ixekizumab and brodalumab in the IL-17 space. If you pick out the two best, if you will, there's been many meta-analyses that go with what I just said. It's not just my opinion, this is based upon data that those four drugs are the best of the best, those two 17s and those two 23s. We have coming likely soon another 17 blocker, bimikizumab, which to me has the best efficacy that we've seen to date for any psoriasis drug. There we have PASI100 numbers in the 70% range for bimikizumab, and that's an IL-17A and IL-17F blocker. If you're interested in the very best of the best, you would be interested in this new drug that's likely to come out, bimikizumab. 

Disclosures: Blauvelt declared financial ties to drugmakers. See full study for details. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

In the phase 3 OASIS-1 trial, mirikizumab, an IL-23 blocker, was superior to placebo through week 52. According to data published in the British Journal of Dermatology, 60% of patients on mirikizumab achieved completely clear skin (PASI100) at 1 year. 

Andrew Blauvelt, director of the Oregon Medical Research Center, spoke with MD /alert about the OASIS-1 trial results and the future of IL-17 and IL-23 blockers in psoriasis. Despite the manufacturer not pursuing regulatory approval, the lessons learned from the success of mirikizumab will be helpful to future drug development in the field of dermatology. 

How was the OASIS-1 trial conducted? 

The initial 16 weeks was pretty straightforward. It was actually 4:1 distribution of patients, where for every 5 patients, 4 of them were on mirikizumab—we call it miri for short—and 1 out of 5 were on placebo. Then, at the week 16 time point, a variety of different doses were studied, and randomized withdrawal was assessed as well. The initial dosing was 250 mg of drug every 4 weeks. Then, from week 16 to week 52, we had patients going into one of three groups, we had them going to a maintenance dose of 250 mg every 8 weeks, or 125 mg every 8 weeks, or placebo. From week 16 to week 52, we were able to assess two different maintenance doses. After that every 4-week dosing, then we went to every 8-week dosing and assessed those two doses. We also assessed the effect of the initial 16-week therapy and how long it lasted with that randomized withdrawal group. 

What were the key findings of the OASIS-1 trial? 

Well, we always like to talk about the primary endpoint first; the primary endpoint was achievement of clear or almost clear on the PGA score, SPGA. For the week 16 number for mirikizumab, that was around 69% versus about 6% of patients on placebo—69% of patients achieving clear or almost clear skin after 16 weeks of mirikizumab. That's the first finding. The other main finding is when we look at the two maintenance doses, and then over time, we actually see the majority 82-85% of patients are maintaining clear almost clear skin on either maintenance dose. Both maintenance doses, 125 mg and 250 mg every 8 weeks, showed pretty much equal efficacy in maintaining clear or almost clear skin at week 52.   

Then the other main data point is the randomized withdrawal group. Here we actually saw about 50% of patients losing that clear, almost clear skin, but it was all the way out, it was 6 to 8 months later when we saw patients recurring who had been switched over to placebo. So, a pretty long time before they had recurrent disease on average. That's kind of what we've been seeing as well with other IL-23 blockers. They're sort of the best class of drugs in terms of keeping psoriasis in check for longer periods of time after the drug is stopped compared to other types of drugs.   

I always personally like to talk about PASI100, completely clear skin. It's a number that patients are interested in too, they want completely clear skin. Lots more talking about PASI100. That number is about 60% at the 1-year time point, which is a very high number. Sixty percent of patients—6 out of 10—achieving completely clear skin at the 1-year time point with either maintenance dose. So again, that's a really significant number as well in this trial.  

What do you want fellow clinicians to know about mirikizumab in psoriasis? 

To me, this drug further supports several concepts. One, IL-23 blockade in psoriasis is incredible. It's a great target. To me, it's probably the best target that we have in terms of giving us the combination of efficacy with essentially no safety signals. You get some, a few, safety signals with IL-17 blockers that you don't see in IL-23 blockers. If you talk about the safest drugs combined with high efficacy and they're dosed infrequently, it's hitting 23 blockers such as mirikizumab—and this again, this study supports all of that—are hitting on all those three cylinders: efficacy, safety and convenience. This data just shows that even further. 

Disclosures: Blauvelt declared financial ties to drugmakers. See full study for details. The study was supported by Eli Lilly. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

An international survey of 180 participants worldwide reached consensus on 20 out of 21 items to give guidance on the use of methotrexate for adults and children with psoriasis.  

Among the most popular items agreed upon during the process was the idea that the dose of methotrexate could be decreased to the lowest effective amount according to treatment goals. It was also broadly agreed that folic acid should be supplemented in all patients, and that methotrexate should be tried, and the dosage increased if needed for at least three to four months to determine efficacy. However, most participants disagreed with the idea that the dosage of folic acid should be increased when increasing the methotrexate dose.  

Astrid M. van Huizen, MD, from the University of Amsterdam, discussed the survey results with MD /alert. 

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What was the idea behind this work? 

The idea was, we found out there's a lot of differences in the methotrexate dosing regimen dermatologists are prescribing for their psoriasis patients. You can read more about it in the study from the Lancet, it was a survey from 2015. And then we thought, well, we think methotrexate is still a very important drug, even in the era of biological treatments. It's relatively affordable, globally available. And we thought we might optimize the psoriasis treatment if we can uniform the methotrexate dosing regimen. So that was the idea. 

What were your findings? 

We found out that it was possible to reach consensus on 20 out of 21 proposals and for improving the methotrexate dose regimen. And you can think about different aspects like whether you should use a test dose, a starting dose, whether you can increase the dose, should you administer it in the oral form or subcutaneously, and whether you can use folic acids. And we made special sub-classifications for elderly patients and children. 

How are providers approaching the use of methotrexate currently? 

A lot of it is based on habits because, well, methotrexate is available for over 50 years right now. So everyone is doing what you're used to doing. And we think that with our consensus statement, we can uniform it, and yeah, different dermatologists can use it in their guidelines as well. So it's some kind of awareness actually to create this uniform dosing regimen. 

In rheumatology, they are more used to it. We aren't brave enough to use a high dose in dermatology. I think so. Yeah. A lot of dermatology is used to the drug, but we are careful, actually. 

How have the newer medications affected the use of methotrexate? 

I think that it really depends on in which country you were asking that question. In the Netherlands, it's usually patients have to use two conventional systemic treatments like methotrexate, cyclosporine, things like that. In other countries, it's more common to get to the biologic quite often. In Africa and other countries throughout the world, in non-western countries, biological treatments are not available at all. So then, methotrexate is very important for them. So it depends, actually. 

What should providers know about this work? 

We don't think a test dose is needed, according to our consensus statement. The starting dose can be 15 mg a week, and folic acid should be supplemented, but 5 mg a week is enough. It does not depend on the dosing of methotrexate you are prescribing. And we think more research is needed for the subpopulations like elderly and other vulnerable patients, children, because we still think that's quite varying in practice, and there's not enough evidence to do a good recommendation about that population. 

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Disclosures: van Huizen declared financial ties to drugmakers. See full study for details.  

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty Images

Extension results from the IXORA-PEDS trial showed ixekizumab provided long-term benefits for young patients with plaque psoriasis beyond what was seen in the initial trial, according to results published in JAMA Dermatology.  

The extension trial included 139 patients through 108 weeks showing improvement in Psoriasis Area and Severity Index and static Physician’s Global Assessment scores. Through this period, 91.7% achieved PASI 75, 79% achieved PASI 90, and 55.1% achieved PASI 100. 

In addition, 78.3% achieved an sPGA score of 0 or 1, while 52.4% achieved an sPGA score of 0.  

Amy Paller, MD, MS, chair of dermatology at the Northwestern University Feinberg School of Medicine, discussed the trial results with MD/ alert.  

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Why was the extension study conducted and did it show any significantly different results? 

We do extensions to try to see if the results that we’re seeing earlier are sustained, especially in the case of a biologic, and they were. But, we also have a chance to look for any new safety signals—there were none—and to be able to look at some of the changes that may take a little longer than just a few months: for example, nails and palmoplantar involvement. That was enabled in this trial. 

The results were sustained with no new signals of safety problems. We also found out that the majority will achieve clearance of nails that was 68.1%, and palmoplantar improvement with clearance was seen in 90%. 

What does this mean for patient care? 

The use of this biologic, and probably others as well for a longer period of time, will achieve changes in nail psoriasis, changes in palmoplantar psoriasis that can take longer, as we continue to follow it out. That encourages us to keep our patients on these to be able to see some of these more difficult-to-achieve effects. 

Did the extension trial show any concerning safety results?

There may be some children who might be hesitant to use the ixekizumab because it’s an IL-17 inhibitor. There’s still an unknown about whether there’s truly any increase in risk of developing Crohn’s disease. Until that is worked out—keeping in mind, of course, that this is the age where we see Crohn’s disease develop, and there’s already an increased risk when one has psoriasis—it’s probably prudent not to start someone who has Crohn’s disease or perhaps even a strong family history of Crohn’s disease on the IL-17 inhibitors. 

What should providers know about this research? 

The most important thing is the concept that these newer biologics are incredibly effective. They’re effective not just short term but long term, including for these tougher-to-achieve clearances, like the nails, palms, and soles. 

In this particular study, there was a big eye on Crohn’s disease and its potential development over a longer period of time. There was one patient in the early months who developed Crohn’s on the ixekizumab, and not the placebo; then, over a 1-year period of extension, there were 3 more who at that point were on open-label and developed Crohn’s. In the subsequent year, there wasn’t a single patient who developed Crohn’s on the ixekizumab. I think that’s important information, which is more reassuring for us than what we saw with the original open-label phase. 

With such positive results, where can this research go from here? 

I don’t know that you can get too much better. Obviously, everybody wants PASI100 and 100% clearance of all areas. But, I don’t think there’s a lot of room for greater achievement. In the future, I think the next step is something, perhaps, that’s not a shot. Because, if you have something oral, it’s certainly more welcomed by many patients, particularly by pediatric patients. However, right now, I think most will take this infrequent injection to get the results that are seen. 

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Disclosures: Paller declared financial ties to drugmakers. See full study for details. 

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty Images

Artificial intelligence is becoming more popular in dermatology and other medical fields. Still, while providers are learning more about the technology, there remains a place for human experience and expertise, according to a study published in the Journal of Drugs in Dermatology.  

An online survey completed by 54 respondents found that 60% were slightly familiar with artificial intelligence, though 81.1% said they had not incorporated it into their practice. In addition, only 27.8% said they believed AI was superior to human experience sometimes, while 94.4% said they would use it in certain situations.  

Vishal Patel, MD, FAAD, FACMS, an assistant professor of dermatology and oncology at the George Washington University School of Medicine and director of cutaneous oncology at the George Washington Cancer Center, spoke with MD /alert about the research.  

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How is AI used in dermatology? 

AI is used in all varieties of ways in our lives. In medicine as a whole, electronic medical records utilize AI. Research data, gathering, and pulling uses AI. In dermatology, specifically, just from the fact that we are an image-based specialty, visual inspection, image capture, photography, and then assessment of that. There are many applications of AI. You can think about monitoring of skin lesions using AI to help calculate or detect differences. We utilize that.  

Now there's a lot of research and work being done in pigmented lesions or lesions that could become melanomas to be able to utilize technology to help us more accurately identify suspicious lesions. It's been utilized and is being studied in pathology and helping to better, more accurately make diagnoses in pathology. And then there's now even genetic material, genetic data around patients, around biopsies, that utilize AI algorithms to help understand what that information really means as it relates to the patient. 

Is there data supporting the benefits of AI over providers alone? 

There’s a lot of evidence around the benefits of AI. Rather than making it a separate dichotomy of man versus machine, we should really think about it as a way to augment intelligence, not necessarily artificial, but augmented intelligence, that this is just a tool to make us smarter and better at our jobs. I'm in no way somebody who believes that AI is going to replace clinicians. But rather, I think it's going to help reduce medical errors and help us provide more accurate and personalized care to patients.  

There has been studies done to compare, for example, unknown diagnoses, skin lesions, and the accuracy of physicians versus a machine that's trained on diagnosis of those lesions. And many, if not most of them, show that the AI algorithms can be superior. But there are definite caveats to that. That training is only as good as that specific question you're looking at. That it significantly improves when you combine the two when you combine a physician's expertise and the machine's algorithm. And that it shouldn't be looked through a vacuum to say that this can just then be applied widely. And I think that's kind of what we also wanted to see with the study, what are people's understandings of what it is and what it can do? 

How would you like to see AI used in the future of dermatology? 

We’re just starting to scratch the surface of its applications, and there are many people who are utilizing it but not as a specialty as a whole. I do think that there’s significant evidence that shows that dermatologists, our clinical suspicion, is not as good as we’d like it to be.  

Or, sorry, our clinical accuracy is not as good as we believe it to be. As clinicians, as dermatologists, when it comes to say identifying a melanoma, or other skin cancers or even non-malignant lesions. We utilize a lot of biopsies to confirm that we have an approach of maybe over biopsying in order to identify those actual suspicious lesions. And I think that's where AI is going to really help not only the dermatologist not miss lesions that they think are benign, and they might miss them, but also to cut down on overtreatment, over-biopsying of lesions that otherwise that the technology can help provide some more data points for the clinician to then understand it. That's probably my most exciting technological advancement that we'll see in our career is to be more efficient and more accurate. And this technology will help with that. 

Is there a challenge getting providers to use the new technology or having patients trust the new technology in their care? 

I think certainly that we have for the last decade or so as this technology has come to the forefront seen a lot of resistance, as people, clinicians believe that this somehow threatens their expertise or what they do. And that has been a lot of our initial work is to, including with this survey, to capture what those concerns are, and kind of debunk and inform people what the technology does.  

On the patient side, we see the opposite. I think people utilize technology and see this as an asset to their care to personalize care as well as more accurate care. I haven't seen that kind of resistance. But on the clinician side, a little bit more so maybe.  

And interestingly, in our survey, we hypothesized we might see that in clinicians who are older who may not have as much experience or comfort level with technology than with the younger generation, those that are just coming out of training, much less resistance and much more of a welcoming approach.  

I do think that there is one large caveat, which is that this technology is not really perfected yet. There is rightfully so a lot of criticism towards it and how we train the technology and the machine learning to be inclusive of all skin types deserves a lot of that training. The images that we have are very bias towards, say patients with lighter skin because that has been traditionally cataloged historically, for decades. And so, a lot of work needs to be done to make sure that we have addressed so that it can be used widely. And clinicians who may not understand that nuance are not utilizing it in an inappropriate way. 

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Disclosures: Study authors declared financial ties to drugmakers. See full study for details.

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty Images

A systemic review and meta-analysis found patients with psoriasis have an increased risk for colorectal cancer, according to results published in the Journal of the American Academy of Dermatology.  

Yun Fu, MD, from the Chang Gung Memorial Hospital in Taiwan, and colleagues evaluated nine cohort studies including more than 10 million patients. The researchers observed a 1.16-fold increased risk for colorectal cancer for patients with psoriasis compared to a control group of individuals without psoriasis.  

Paolo Boffetta, MD, MPH, Associate Director for Population Services at Stony Brook Cancer Center and a professor at Stony Brook University, spoke with MD /alert about the study and what dermatologists should be doing to protect their patients. 

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What was your impression of this study establishing a link between psoriasis and colorectal cancer? 

Basically, all the studies were quite consistent in showing this effect. However, this effect is not very large. It is only about 15-16% higher than the average person with all the other factors, age, etc. So, although there seems to be an association, which has been, as I said, observed, in these several different studies, the magnitude of the risk is modest. 

The first results were published in 1999. My study was the second one published in 2001. So more than 20 years ago now. These two studies found the association. However, you know, this was a bit unexpected. So at that time, we couldn’t really conclude that we knew for granted that the association was clear. There can be many reasons why there are small increases or decreases in the results of individual studies. But then, after my paper in 2001, there has been another six studies, and they all confirmed the early results that I found, and also the very first data found. So now, the evidence 20 years later is much stronger. And we can conclude that there is an association, although as I said, it’s not strong. And it’s probable we could also say it’s not psoriasis causing colorectal cancer, but there are probably physiological or pathological mechanisms we commonly see. So the diseases are, or they seem to be really associated one to the other. 

Do we know what causes this connection? 

We don’t know too much. We have a few hypotheses. One hypothesis is the role of inflammation and inflammatory markers that are centrally very important in psoriasis. But they are also important in the process of cancer development in various organs, in particular in the colorectal. So it’s possible that a number of immunological factors including some particular type of immunological cells. And the product of the sense they’re called cytokines may be active in stimulating the proliferation, the growth, both at the level of the skin, where psoriasis occurs, and at the level of the colon, or the rectum. That’s one hypothesis. So some inflammatory and even biological mechanisms that are common in common between the two diseases. However, we don’t know exactly which of these factors may be at play here.  

And then the second hypothesis is called the microbiome. So, the population of bacteria that are present in all organs, but in particular in the gut, in the colorectum, and in the skin, may also play a role. And this may be modified. So it’s possible that the development of psoriasis modified the population of bacteria that may, in fact, also be in the colorectum, or vice versa. So they may produce different metabolites and different factors that may, again, be involved in the development of the comorbidities.  

Should dermatologists encourage patients to be screened for colorectal cancer? 

It’s very important that psoriasis patients do attend screening programs, and possibly they have a different schedule, like maybe a screening every five years, and not every ten years, as is the case recommendation for the general population average of the general population.  

And then there are other ways to reduce the risk of colorectal cancer, primary prevention. Which mainly is reduce body fat, so reduce weight and avoid overweight and obesity, increased physical activity, and have a healthy diet with whole-grain fruits, vegetables, and maybe a reduced amount of red meat. So all these are advices that are good for the population at large. But it may be particularly important for people who have at least a slight increase, as I said before. 

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Disclosures: No authors declared financial ties to drugmakers. 

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty Images

Patients with psoriasis are at an increased risk for developing venous thromboembolism and peripheral vascular disease, according to a study recently published in JAMA. 

MD /alert spoke with Joel Gelfand, MD, MSCE, James J. Leyden Professor of Dermatology and Epidemiology at the University of Pennsylvania, about his clinical experience managing cardiovascular risk factors in patients with psoriatic disease. Dr. Gelfand highlighted the importance of early and consistent screening, especially in the primary care setting, for patients with psoriatic disease. 

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Can you explain the clinical significance of increased risk of venous thromboembolism and peripheral vascular disease being associated with psoriasis? 

I think that when we think about a study that's looking at the incidence of venous thromboembolism and pulmonary embolism, and people with psoriatic disease, we should really interpret it in the context of all the data out there for other thrombotic complications, including cardiovascular events, and stroke, as well as cardiovascular mortality. Looking at one thing in isolation,  may seem to be a pretty rare finding for the patient, perhaps not something to be too concerned about, but when we look at the variety of different cardiovascular events that patients with psoriasis are more prone to, particularly as the disease gets more severe, that then does culminate in terms of more significant risks to patients over their lifetime.  

What that really translates to for clinical practice is number one is patients with psoriasis should be aware that they appear to be more prone to developing cardiovascular complications, whether it be venous thromboembolic disease, myocardial infarction, or stroke, and that this risk seems to be more important or more significant, the more severe their skin disease is. The important thing to know is that we feel that controlling traditional cardiovascular risk factors is part of the solution to lowering this risk and having better health outcomes for the patient.  

We know from a variety of lines of research that people with psoriasis tend to be under screened for additional cardiovascular risk factors like their blood pressure, testing for diabetes, testing for cholesterol. The first step in this process is making sure the patient's traditional risk factors have been identified and managed appropriately. By doing that, we think we will probably resolve a fair amount of the excess risk patients are experiencing. Then, an open question is whether or not successfully treating psoriasis over the long term will result in a lowering of these complications that we see, and there the jury is still out. 

Can you explain the connection between psoriasis and cardiovascular disease? 

This is a great question. So one is, there's a variety of different ways of which it's hypothesized that psoriasis promotes cardiovascular disease. For example, the platelets of people with psoriasis tend to be more sticky. That means they're more likely to clot and that of course, can cause thrombotic complications. Psoriasis also seems to promote chronic inflammation in blood vessels. This type of chronic inflammation, then processes cholesterol that builds up in vessels into atherosclerosis and puts it at risk for plaque rupture, and then cardiovascular events. Then finally, there's some degree of shared genetic risk factors as well. We're looking at a multifactorial problem that's going on for patients with psoriatic disease.  

The second part of the question is really why are people with psoriatic disease under screened for traditional cardiovascular risk factors like blood pressure, diabetes, and cholesterol, and sometimes we think is sort of the pattern by which people with psoriasis get medical care in the United States, a large percentage of patients with psoriasis actually don't see a primary care doctor, a lot of them are just seeing a rheumatologist or dermatologist for the management of their chronic disease. Therefore, these screenings are not being done in a specialty care setting.  

The second part of this is that when someone lives with a chronic disease, that could become burdensome and a little bit overwhelming, and a lot of times other health issues don't have the same degree of priority. It really is incumbent upon us to educate patients about this issue, institute these simple screenings for them or encourage them to see a primary care doctor for the screenings, and then make sure these factors are treated appropriately. This could really improve the patient's health and wellbeing long term. 

What are some next steps to further understand the effect of increased cardiovascular risk on patients with psoriatic disease? 

I think the key question is whether or not appropriate and successful management of psoriatic disease over the long term will result in a bending of this comorbidity arc, if you will, will patients have fewer cardiovascular events and strokes and things of that nature, maybe a lowering the risk of diabetes, if we control the inflammation in their skin, and then the joints if the joints are affected. Those studies are very difficult to do. Traditionally, cardiovascular trials are very large, you may have several thousand patients, followed for an average of about five years, randomized to treatment versus placebo. That type of study is very difficult to do in people with psoriasis. We're not going to put them on a placebo for five years for their psoriatic disease. There are certainly some emerging data from my group and from other research labs in looking at randomized placebo-controlled trials of the effects of our therapies on a variety of cardiovascular pathways, whether it be their lipid metabolism, markers of inflammation related to cardiovascular disease, or imaging of cardiovascular disease. The findings are kind of nuanced, but in general, many of our therapies do seem to have some impacts that seem promising for lowering the risk of cardiovascular disease. Ultimately, patients don't really care about lowering a biomarker or an imaging marker, we really need to know about events. That's the area of research that's most needed at this point in time. 

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Disclosures: Gelfand reports consulting roles with Abbvie, BMS, Boehringer Ingelheim, Celldex, FIDE, GSK, Happify, Lilly, Leo, Janssen Biologics, Neumentum, Novartis Corp, Pfizer, UCB, Neuroderm, Regeneron, Trevi, and Mindera Dx, as well as honoraria and research grants. Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. 

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

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The approval of biologics for pediatric psoriasis patients has improved the quality of life of these young patients and given providers treatment options with better safety profiles than some of the previous choices in their armamentarium.  

A systemic review and meta-analysis of five randomized clinical trials published in Pediatric Dermatology found the odds ratio of achieving a 75% improvement in Psoriasis Area and Severity Index (PASI) score at initial follow-up, typically after 12 to 16 weeks of treatment, was 12.37. The odds ratio of an adverse event was 0.95 at initial follow-up for patients treated with biologics compared to placebo or non-biologics.  

Amy Paller, MD, MS, the chair of dermatology at Northwestern University Feinberg School of Medicine, told MD /alert that these medications’ impact in real-world settings reinforces their value for providers.  

What is the current status of biologics for pediatric psoriasis? 

Fortunately, there’s been great progress in the availability of systemic agents to treat pediatric psoriasis. We started off many years ago publishing on the very first biologic, which was etanercept given weekly, and showing very good results for pediatric psoriasis.  

It took until I think 2016, If I remember before etanercept was even approved by the FDA, to be able to use. We still don’t have adalimumab approved by the FDA for use, even though its use has been extensive off-label for pediatric psoriasis. But now we have three others that are approved down to six years of age: Ustekinumab, ixekizumab, and secukinumab that have all been fairly recently approved by the FDA. There are many others now that are available and have in some cases been available for several years for adults with psoriasis that are in testing, and we hope will be available in the years to come as well for our children and adolescents who have psoriasis. 

How do providers choose biologics for these patients? 

There really isn’t an algorithm per se. Very much, it’s that shared decision-making between the physician and the family. There are advantages and disadvantages of each. Of course, the advantage of etanercept, if we decide to go with a biologic, is that it’s approved down to four years of age in the United States, and it’s been around the longest. But there are disadvantages because it’s not as effective as the others and it has to be given weekly.  

So for anybody who has to get an injectable, that’s not as desirable, but still several use that, in some cases, because they’ve been using it for years and it’s still working. Even with adalimumab, it’s an every two-week injection. Whereas if you go to ixekizumab and secukinumab, those are given every four weeks. If you go to ustekinumab, it’s given every three months. And there are some real advantages for families, particularly with younger children, to be giving something only every three months because it can be quite stressful to give a medication. So, the every one month and the every three months do offer advantages in terms of the infrequency of having to give the dosing.  

We’re also getting away a little bit from the TNF inhibitors, which have seemed to have the highest risk for tuberculosis susceptibility. But on the other hand, the TNF inhibitors have been wonderful for joint disease and are still the go-to for our pediatric rheumatology colleagues. So for our patients who have both psoriasis and psoriatic arthritis, and about 1% of the children, adolescents who have psoriasis also have that juvenile idiopathic arthritis subset, that is the psoriatic arthritis, the TNF inhibitors actually can offer a great advantage. They tend to be a little bit better, for example, than ustekinumab, which has the advantage of being given every three months, but just it’s probably not going to be as effective for the joints, although certainly many patients do okay with their joints with ustekinumab.  

But I will say the overall consideration that I didn’t mention is access. For some patients, insurance will only cover this one, or that one, and then that may be the one that we have to go with, especially as our first line if we’re choosing that.  

What additional work remains? 

I do really think that what I’d like to see most is, first of all, oral medications that are safe and highly effective. Ideally, those that don’t require the recurrent blood test like we have to have with methotrexate. I’d also like, frankly, to see better topicals. We know that the vast majority have mild to moderate psoriasis in the pediatric ages. The range is anywhere from about 11 to mid-20s that have moderate to severe disease depending on the results that one sees in different countries. And that means that the majority of our patients are still using topicals. And nobody really loves these topicals. You have to continue them for a while. We know that if you stop them, it comes back if they’re effective. We’re using potent topical corticosteroids to treat this. So I’m looking forward to seeing some other topicals coming out that maybe are as effective as the topical steroids that we’re using. But we can get away a little bit from steroids.  

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Disclosures: Paller declared financial ties to drugmakers. See full study for details. 

Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty Images

According to a recent study published in the New England Journal of Medicine, tapinarof, a steroid-free topical cream showed superior control of plaque psoriasis in phase 3 clinical trials when compared to placebo. 

MD /alert spoke with Mark Lebwohl, MD, dean of clinical therapeutics and professor of dermatology at the Icahn School of Medicine at Mount Sinai.  

Dr. Lebwohl highlighted the importance of steroid-free treatment options for psoriasis in order to avoid some of the frustrating and also clinically problematic common side effects that come from using steroids for this chronic condition. 

What led to the development and study of tapinarof as a new treatment for psoriasis? 

So for many years, the treatments we go to for psoriasis overwhelmingly are topical steroids. The problem with topical steroids for a chronic disease is that they have side effects. They thin the skin and end up resulting in... probably the worst side effect is stretch marks which are irreversible, but they have many other side effects as well. There's a condition called perioral dermatitis, which is like an awful acne-type rash on the face that is severe, and no matter what you do for it keeps getting worse until you stop steroids for a very long time, over a year, often.  

They also cause the atrophy of the skin so that the collagen in the skin is reduced, which is the cushioning that prevents blood vessels from breaking up, and so people get purple marks on their skin called steroid purpura and a whole host of other side effects that are caused by steroids. Again, when you use them for short periods of time, it's a non-issue, but when you use them chronically, and psoriasis is a chronic condition, that's when you start getting in trouble. The particular parts of the body where we really know not to use them like the face, armpits, groin, under the breasts, because those are thin skin to begin within, and as you use steroids they get thinner and thinner and that's when you get in trouble.  

So we had a real good reason to look for non-steroids and there are a number of non-steroids already on the market: calcipotriene, tazarotene are both approved for psoriasis. They, unfortunately, are also highly irritating specifically on those thin-skinned areas like the armpits, groin, and face. So we don't like using them in those areas because they cause irritation to many patients. So this is the first new non-steroid. There's one other in development for psoriasis that has been studied for psoriasis, for the purpose of getting it approved at the FDA. And, and since this is the publication of the phase three trials with that drug, which is called tapinarof, it is a novel mechanism of action. It is as strong as potent topical steroids without having steroid side effects. 

How was the study designed?  

So you know, the point of the trials was to get FDA approval of the drug. So we're looking for something that is effective and safe. The studies were designed to reach those conclusions. The design of the studies, if I remember right, this was a 12-week study, and the drug was applied daily. What we showed at the end of the 12 weeks is that it was indeed superior to placebo. The degree of superiority is comparable to strong steroids. In terms of safety, we wanted to show that it didn't have serious side effects. Indeed, there was one side effect that stood out, which was it was called folliculitis, but it's almost a pimple-like reaction, which happened to about as many as one out of five patients, but it was mild to moderate and it actually did not keep patients from continuing to participate in the trial, or even from going into what's called the open-label extension, where after the first 12 weeks, patients are given the opportunity to stay on the drug if they didn't clear completely. 

What were the key findings? 

So the key findings were several one was, again, highly effective, superior to placebo, comparable to strong steroids at week 12. The second point was the safety that I already discussed. The third point was that in patients who cleared completely at the end of 12 weeks they stopped the drug. Those patients continued to remain clear, for a median of 115 days. So almost four months later, after stopping the drug, they stayed clear. So it's a very remittive effect, and finally, a durable effect. The people who, who did not clear completely but still had a little residual disease, but stayed on the drug, were allowed to continue on the drug, and they continued to maintain their improvement for several months after the end of the placebo-controlled trial.  

What should clinicians take away from this research? 

Hopefully, we will have this drug available sometime in the near future, and it will be a very useful substitute to topical steroids. Psoriasis is a chronic condition, and we don't like to use topical steroids chronically. We now will have a non-steroid that doesn't have steroid side effects. You know, one of the side effects I didn't mention earlier is if you apply topical steroids chronically to the eyelid or to the around the eyes, cataracts and glaucoma are side effects. So there are many serious side effects that we want to avoid if we possibly can, and so this will be a welcome addition to the armamentarium of treatments we have against psoriasis. 

Disclosures: Lebwohl declared financial ties to drugmakers. See full study for details. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

For several years secukinumab has been a reliable treatment option for patients with plaque psoriasis. Despite its success, researchers found bimekizumab, a monoclonal antibody that inhibits both IL-17A and IL-17F, could prove more effective and as safe as secukinumab.  

Mark Lebwohl, MD, Dean of clinical therapeutics and professor of dermatology at the Icahn School of Medicine at Mount Sinai, discussed the results of a recent study that showed 61% of patients prescribed the newer medication reached PASI 100 at week 16 and 67% achieved the outcome at week 48.  

Lebwohl said that while there is an increased risk of yeast infections associated with bimekizumab, they can be addressed without interfering with the treatment process.  

What was the idea behind this research? 

Secukinumab is one of actually one of the most effective treatments we've had for the past decade for psoriasis. It blocks a molecule called IL17-A, which we know plays a major role in the treatment of psoriasis. In addition, you know, we know now that it is as safe as we thought it would be because nature has done the experiment for us. There are people born with that IL-17 who get only one side effect is yeast infections. So, it's a fairly benign drug. Works by mechanism that's pretty safe, and is very effective, and has been one of the most commonly prescribed treatments for psoriasis for the last almost decade. 

Well, bimekizumab is a molecule that blocks IL-17 A and IL-17F. So, it has that extra kick where it blocks a little more of the IL-17s and was introduced for psoriasis for that reason. And it in fact appears to significantly more effective than secukinumab.  

In addition, it's showing us data that are better than any that we have for psoriasis to date, as well as data for psoriatic arthritis, which is not yet close to approval for psoriatic arthritis. But the data we have so far makes it look like it’s more effective for psoriatic arthritis than any of the other biologics that we have. So that was the impetus for doing this study.  

This study confirmed what we thought. As one would expect, if you block IL-17A and IL-17F what we thought we would find ended was a higher rate of yeast infections. So, in the various studies that bimekizumab underwent, the frequency of yeast infections as much as 20%. So, that is the one drawback it has. But they were mostly mild to moderate, hardly ever interfere with the patient continuing on the drug, and are very easy to treat. So that’s what we saw in that study.  

Who is the best candidate to receive bimekizumab if approved? 

First of all, there are many patients who cleared completely on secukinumab. And, you know, they’re going to continue on the drug that patients who are doing well, are going to continue it. Patients who are doing okay, which is a lot of patients, there are very few patients who don’t get somewhat better. But patients who still haven’t reached the targets they want. You know, patients want to be clear or very close to clear. And they want to not be suffering with joint pains. And those patients would be good candidates for a more effective drug, even though the frequency of yeast infections is somewhat higher.  

Are there more serious adverse events to be aware of other than yeast infections? 

The yeast infections were more commonly oral, so thrush was common. Genital yeast infections can occur. They’re very easy to treat. The treatment for genital yeast infections is a single 150mg fluconazole pill. When you have it in the mouth you can either use clotrimazole troches, or you can use fluconazole as well. But usually we treat patients for longer. The guidelines that have been written suggest at least seven days, although I always say I didn't know those guidelines when I started seeing patients with oral thrush on secukinumab and ixekizumab, which also blocks out IL-17. And I would give patients three days of fluconazole and they always got better. So you know I think that these are very easy to treat infections. In terms of things that you really need a lot of experience to learn, we're finally now starting to get the data on adverse events like malignancy. And it looks favorable. None of the IL-17 blockers mention the word malignancy in their package inserts. Certainly, in animal models and people who are deficient IL-17 there’s not an increase in cancers.  

And now the data is coming out from large registries. What we are seeing is there is no increase in malignancies in patients treated with IL-17 blockers. We worry about adverse cardiovascular events. We know that psoriasis patients are susceptible to myocardial infarctions because of the inflammation associated with psoriasis. And we're now just starting to see some data suggesting that blocking IL-17 will indeed be preventive in that arena. Although that data is not, you know, completely established yet. Hopefully it will be the case.  

So, you know, there's some rare side effects that you only get reported when a drug has been on the market and for many years and using thousands of patients. And who knows if that will happen, but so far it doesn’t look like it is.  

What do these results mean for patient care? 

It does appear to have a sustained effect. In fact, the PASI 100 numbers at the primary endpoint, 16 weeks, actually increased by week 52. That, of course, is not a placebo control period. So, it’s a sustained, durable response. The other thing about the drug is it's very fast. We see three-fourths of patients achieving PASI 75 at four weeks, so it's a very rapidly acing drug. So many positives to this medication.  

What more work needs to be done in this area? 

I think there always will be a need for better drugs. There are now trials of drugs that are in pill form rather than injected. There are drugs that are given less frequently. We still can't use the cure word, meaning you know, you give a patient a treatment and their psoriasis never comes back. We have a lot of improvement in the realm of psoriatic arthritis, where we are actually not doing that well. I mean primary endpoint for many of the studies is ACR 20 with bimekizumab we see very high responses in ACR 50 and even decent ACR 70 responses. So, we have a lot of room in psoriatic arthritis for improvement. 

The FDA has approved secukinumab to treat patients over the age of 6 who have moderate to severe plaque psoriasis. 

Alan Menter, MD, Chair of Dermatology, Baylor University Medical Center, spoke with MD /alert about the impact of this approval.   

What was treatment for these patients like before this approval? 

There was very few biologics approved for children prior to Cosentyx being approved. One of its competitors, the IL-17 agent Taltz, has been approved for children previously and it’s an IL-17 agent. So it's nice to have a another quality agent like Cosentyx for children. You know childhood psoriasis is not a very common problem, but it once it happens it's very devastating for both the child and for the parents, so it's very important if the patient has moderate-to-severe psoriasis, which means over 10% of their body involved. In the old days we would use cyclosporin. But cyclosporin has many many side effects. So you can’t do it long-term, whereas Cosentyx has very good safety data for long-term use. 

What does it mean to have two biologics available to prescribe to these patients? 

You know you, we cannot predict which drug, which of the two drugs, Cosentyx or Taltz is going to be best for which person. We don't yet have a test that'll allow us to choose the correct drug for the correct person. Like we have 11 biologic drugs for adults now. We have four TNF alpha drugs. We have one IL12-23 drug ustekinumab. We have three IL-17s, and three IL-23s. The big question when we see a patient with moderate to severe psoriasis is which drug is likely to work best in which patient.  

Cosentyx and Taltz are very, very similar. They both are IL-17 inhibitors and it's nice to have a second systemic biologic drug available for children.  

How comfortable are dermatologists prescribing these medications for younger patients? 

I think that you know it depends on whether they're a pediatric dermatologist or not. There's a shortage of pediatric dermatologists worldwide. So, a lot of us who are not qualified in pediatric dermatology will treat children anyway.  

So, I would believe that once we have all the safety data in adults, it’s going to be equally safe in children, and dermatologists should feel comfortable prescribing Cosentyx for children.  

But if someone has been treating a lot of adults with Cosentyx, I think they should feel very comfortable treating children, although the dosing is going to be a little different based on the children weight, etc.  

Is there specific safety information that providers should be aware of when prescribing this medication? 

I don't think it's any different to what has been available for adults at all. In fact, if anything, the risk of side effects in the childhood population is much less than the adult population.  

Well, I mean the obviously [these] have an effect on the immune system. But the benefit of the IL-17 agents like Taltz and Cosentyx is it's attacking one pure cytokine and the rest of the immune system was left totally intact. So, the old agents were immunosuppressive. The newer agents, like Cosentyx, are not considered immunosuppressive. There's a slight increased risk of infection in all the biologic agents, but it's very low indeed.  

What are the biggest changes in the guidelines for treating pediatric patients with psoriasis? 

A huge big change has been a huge big advance over the last 10 years or even over the last five years. When we did the guidelines previously, there was no IL-17 or IL-23 drugs available whatsoever. So, in the last 10 years, we’ve had a major advance. Dermatology lagged behind rheumatology, gastroenterology in the field of biologics. All four TNF-alpha agents, Enbrel, Humira, Remicade, Cimzia were all first approved for joint disease before they were approved for skin disease. But now I think we’ve leapt ahead with all the new IL-17 and IL-23 agents.   

Is there more work to be done to help these patients? 

I think the fact that we’ve got the safety data in adults over five years for both Cosentyx and Taltz tells us that the chartered safety should be equally positive. And, you know, we now have one pediatric drug for atopic eczema, or a biologic for atopic eczema. There’s going to be a whole lot more coming. And, you know, because atopic eczema is much more common in children than childhood psoriasis is. But having now two quality IL-17 antagonists for children is really positive indeed. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

A new vehicle-controlled study found that patients with psoriasis who responded to treatment with calcipotriene/betamethasone dipropionate foam and continued with twice weekly use spent longer in remission and their risk for relapse was reduced.  

Leon Kircik, MD, clinical professor of dermatology at Icahn School of Medicine at Mount Sinai, Indiana University Medical Center, and medical director at Physicians Skin Care, DermResearch, and Skin Sciences in Louisville, Kentucky, spoke with MD /alert about the trial and what it means for patients.  

What was the idea behind the research? 

This is very exciting because this is the first time that we had a formal clinical study to look at a maintenance dose long term for psoriasis patients with a topical treatment. We always have an idea of how to manage those patients, but really never confirmed with a clinical study. So, in this study, what we did, we looked at twice weekly Enstilar foam, which is calcipotriene, betamethasone dipropionate combination up to 52 weeks and how those patients did with that twice weekly. If they were in remission, how fast it took them to get into remission and then how fast the disease flare.  

How was the study conducted? 

First, the first four weeks we did those patients, the inclusion criteria was at least mild, but they could have been moderate or severe. And then they had to have at least 2 to 3% body surface area. And then what we did was we treated them with Enstilar foam for the first four weeks. After that the responders who had at least two great improvement and they were clear, almost clear, were put on the long-term maintenance phase.  

Now, of course, those who did not respond there is no— it doesn’t make sense for them to continue since there is nothing to maintain, right? The whole purpose is to see those patients who responded to the treatment, how they will do for the next year, 52 weeks, if they continue to use the drug twice a week.  

And this type of study has been done before. But what has not been done before that it was vehicle controlled. So, it was a multicenter, vehicle-controlled study that we actually had all over, not only in the USA and Canada, but also in Europe.  

And what they did was the patients continued their treatment. Either they were divided into two groups, either the Enstilar or the vehicle foam twice a week maintenance treatment. And that’s what we wanted to see. And those who had a relapse, and relapse was defined as mild or a number 2 on a physician global assessment. And if they had a relapse, they got the rescue treatment, meaning they continued it every day. They used it every day. And if they didn’t, they continued. And they were allowed to have two relapses. Otherwise they were discontinued if they had more than two relapses during the 52 weeks. And we looked at them once a month.  

What were your findings? 

What we found out that basically patients in the active group who got the Enstilar they had 41 extra days in remission compared to the patients who were on the reactive group, meaning who were on the vehicle arm. So definitely there was some evidence of benefit to use the drug twice a week all the time rather than to have a reactive group, meaning to treat them when they flare.  

So, when you look at the number of the rebounds within two months after discontinuation of the open label, treatment was seven in the reactive group and six on the proactive group. And the relapse treatment was four for the proactive group and 17 on the reactive Group. So basically there is benefit to continue the medication twice a week on a regular basis rather than to react to each flare. Rate of relapse was reduced by 46% in the proactive group compared to the reactive.  

What does that extra 41 days mean for patients and their ability to manage their symptoms and live their lives? 

When you think about it, maybe that many days is not too much for us as people who don't have the disease. But we have to consider the quality of life, the impact of psoriasis on patient’s quality of life Patients, especially if you have an area under, for example scalp, you know those patients are miserable. They cannot wear dark colored clothing because all the white scale falls on them.  

If it's a summertime people want to wear some shorts, some short sleeves, go to the beach, or even a lot of the regular public doesn't know about those psoriasis that it's not a communicable disease. People think that it's a communicable disease. They cannot or they don't want to touch their partners. They cannot have intimate relationships. Older patients all the time, they say my grandchildren doesn't want to. They don't want to come and give me a hug or give me a kiss, right? So, the impact of psoriasis is incredible on patient’s quality of life. So even if you have one day of extra day of having a clear skin, what we call those happy days, it's very, very valuable to those patients.  

Are there safety concerns with the treatment? 

There were no signals really between the two arms: those who had the vehicle and had the real drug. And also they did the HPA axis suppression studies. That means that because there is betamethasone, which is a topical steroid, they wanted to see if the topical steroid is absorbed or it doesn’t have any negative impact internally. And that was not a problem either. So really, overall, there were not any significant safety concerns. 

Where does the research go from here? 

Well, in all honesty, this is something that we've been doing it for several years. It's not sort of a secret. But it's the first time that we sort of confirmed that what we are doing is correct and it's beneficial in a formal, vehicle controlled, multicenter, clinical study. So that's really the benefit of this study that shows that what we have been doing is not wrong, is not harmful, and it's beneficial to the patients. And hopefully it will also help on the payer side who pay for the drugs that if we are using it for a long term over a year, but it's twice a week, not every day, it’s actually beneficial in the long term as well, because it will cut the expense of treating a flare all over again rather than having the maintenance treatment.  

Disclosures: Kircik reports investigators grants and honoraria for consultant and speaking roles with Leo, the drug’s manufacturer. Kircik also reports additional pharmaceutical disclosures unrelated to the study. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

For patients with mild to moderate plaque psoriasis with 5% to 10% of Body Surface Area (BSA) involvement, treatment options remain limited to topicals or phototherapy. A new study assessed whether apremilast, which is approved to treat moderate to severe psoriasis, could be effective among patients with more mild disease.  

Kim Papp, MD, PhD, a dermatologist and president of Probity Medical Research in Ontario, spoke with MD /alert about the results from the ADVANCE trial.  

What was the idea behind this study? 

As everyone might recall, apremilast was developed for the treatment of moderate to severe plaque psoriasis. And in those studies, it demonstrated definite capacity and ability to treat the moderate to severe plaque psoriasis population. It was also seen, and is perceived to be, a very safe treatment option because there is no requirement for screening for tuberculosis, for example. There’s no need for monitoring. And that makes it a very attractive proposition both for prescribers and for patients.  

The biggest void that we have in the treatment of plaque psoriasis is really not so much the moderate to severe group where we have a number of options that are all very competent. What we are looking for and I would say in desperate need of are effective treatment options for patients who have lesser disease burden. And by less, we mean that the surface area of involvement is lower.  

So there is a range of patients and probably the majority of patients where topical therapy is not going to be efficient or effective. So patients may have say, 3% or 5% of the body covered and you'd say just on the face of it, ‘Oh well, that's easy.’ Uh, no, because it's not in one patch. It's going to be scattered either in small papules or in small plaques that could be quite widely distributed over the body surface. And that makes topical treatment very inefficient. And phototherapy, of course, is not without its own disadvantages. It may be effective. But it does have disadvantages. And so we're waiting for another option. And that's where apremilast fits into this category because our risk benefit profile is certainly, I think, very evident. We don’t have monitoring. We’re not worried about tuberculosis, we’re not worried about all these other things that may be causes for concern in patients who are treated with other systemic agents. And so this is just a nice way to fill in that gap. 

So the study was really just completed to demonstrate the safety and effectiveness in treating this population. And not surprisingly, we find that in fact apremilast is indeed adequately, suitably, appropriately, wonderfully competent at treating patients who have less burden of disease, so that range of patients with, say 5 to 10% BSA of involvement. And the side effect profile is virtually identical to what we see in patients who have more severe disease, and that's largely GI and tolerance issues. 

I would also remind everyone that because of the way the adverse effects are coded. It's through the metro code. It's actually taking a very broad funnel of complaints or quotations, adverse events and narrowing them into a very small frame of reference. So for example, when we talk about diarrhea, diarrhea constitutes, for example, a patient who may go from one bowel movement a day or one bowel movement every two days, both of which are in the range of normal, to having a bowel movement every day or two bowel movements a day. It hasn't changed the range of normal, but because there has been a change of frequency and because we as investigators, we are actually soliciting these kinds of changes, if they happen we wanted to know, that's recorded and that will eventually get codified as being diarrhea. 

Now, there are patients who truly experience diarrhea in the common sense of the word, for the most part it's not the diarrhea that people would commonly think of as being diarrhea. And similarly when we talk about nausea and vomiting, mild queasiness that may or may not be associated with taking the drug also gets recorded or funneled into this common medical term of nausea and vomiting. So one always has to not take the face value of the terms that are applied. One sometimes has to look behind the scenes to actually get a true sense of what the reality of the situation is. Nonetheless, this is a quick overall arching summary. The study was conducted to give clinicians some guidance as to the effectiveness of apremilast in treating patients with less severe plaque psoriasis. And less severe, in this instance, means patients who have less than 10% BSA of involvement and more than 5% BSA of involvement.  

What were your findings? 

We found that tolerability was the same as is the case with patients who have more severe disease and those of us who see patients daily are hopeful that we that Amgen will be successful in extending the approval so that we have a better, more efficient, effective therapeutic option for treating patients who are really in high need of effective therapy. And that group of patients who are in high need are just those who have that less severe burden of disease.  

Looking forward, where is the field of psoriasis research headed?  

Because the therapies are fairly effective and we have a number of options, there’s kind of a saturation point. I don’t think we’ve reached the end of the road. There still will be a number of explorations occurring, and certainly we’re already seeing more exploration of new pathways, such as sonelokimab, and new molecules. So, I don’t think we’ve reached the end of the road. We’re still looking for the Holy Grail because not everybody responds to any of the treatments that we have. Some people are just very resistant. We see a growing number of those cases, whether it’s a selection effect or whatever, we don’t know.  

There are also many facets to psoriasis. Psoriasis should be considered as a kind of an amalgam or composite of entities that have significant overlap. We have psoriatic arthritis, for example, and we see that for many of the agents that are effective for plaque psoriasis, they're also effective for psoriatic arthritis. However, they're not uniformly effective. So, one patient may find that in any given patient, they may have their cutaneous manifestation well controlled, but their joints not as well controlled, despite the fact that the drug their on to treat their cutaneous disease is a very confident agent for treating their joint disease, and vice versa. There are patients whose joints are marvelously controlled with the treatment, but their skin is not. And that differential response means that we’re still looking, trying to find something for those individuals. And there are a number of them where we can actually control both of those aspects in a comfortable and efficient manner.  

We have another group where we have axial disease and psoriatic axial is a little bit challenging because it’s an overall of typical quotations. Psoriatic arthropathy, which is predominantly an involvement of enthesis, so that’s where the ligaments or tendons actually insert into the bone, which appears to be the fundamental site of action of psoriatic arthritis. And then there’s another condition, which overlaps and may be somewhat related and maybe not. I’m not an expert in that area, but my clinical impression is that they’re not really related, and that’s ankylosing spondylitis. So, there has to be some considerable overlap because ankylosing spondylitis is not commonly present, typically has a specific HLA associations that are not as common or prevalent in the psoriatic population. So, it’s an interesting juxtaposition of these inflammatory arthroses. 

Having said that, there are patients who have ankylosing spondylitis as well as axial and peripheral joint involvement with classic psoriatic arthritis. And we don’t have agents that are likewise consistently effective for treating both of those aspects. So, we have molecular entities, IL-17 blockers, for example, appear to be effective, as are TNF blockers effective in treating ankylosing spondylitis and psoriatic arthritis. And yet, we have patients who are on TNF antagonists or IL-17 antagonists who have one or the other of those manifestations well controlled, but not both. And it becomes a challenge. It’s an extraordinary challenge to treat these patients because we’re always trying to balance things. Trying to get the maximal benefit without having to all of a sudden go to polypharmacy. So, there will be ongoing research and at least I would certainly support, encourage ongoing exploration to find new pathways, new molecules that will give us and give our patients a better opportunity to optimize their treatment, both to have effective and uniformly effective as well as safe therapies.  

Disclosures: Papp reports consulting, speakers bureau, steering committee and advisory board roles, and research grants and honoraria from Amgen. Papp also reports additional pharmaceutical disclosures unrelated to the study. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Treatment with sonelokimab, a novel tri-specific Nanobody targeting IL-17, resulted in clinically meaningful and statistically significant improvements among patients with psoriasis, according to a phase 2 study published in The Lancet.

Kim Papp, MD, PhD, a dermatologist and president of Probity Medical Research in Ontario, spoke with MD /alert about the novel treatment and the study findings.

What was the idea behind your research?

Sonelokimab is a novel molecule being a nanobody. So, the structure of a nanobody is you have, your active components, which in this target IL17-A and IL-17F. That particular part of the nanobody actually combines with albumen or attaches to albumin, which is then the carrier molecule if you will within the body. The nanobody is administered, it binds to the albumin, it is then carried to the site of the action where in this case unlocking effectively binds IL-17A and IL-17F. So the purpose of this study was to demonstrate both the safety and efficacy in a dose ranging study. Placebo was the control. But we also had an active comparator secukinumab.

What were your findings?

The results of this study show that at the higher doses sonelokimab was very similar to secukinumab in terms of its efficacy. And typical of IL-17 inhibition we saw with sonelokimab a dose related increase in the presentation of oral candidiasis. This is just a known consequence about IL-17 blockade and just further, if you like, exemplifies or demonstrates that in fact it is a very competent blocker.

This is an early phase study. It’s a phase 2 study so it was not designed to demonstrate superiority. Secukinumab was simply selected as a reference to gauge how effectively sonelokimab works and that was the real reason for including secukinumab as a comparator.

It will take further studies in the phase 3 development, assuming that moves forward, where one will actually be able to demonstrate non-inferiority or superiority as the case may be. But those determinations will require more studies and larger studies.

Were there surprises in your findings?

I would say there were no surprises, but it was gratifying to see that we have another opportunity to possibly take advantage of the nanobody which is about the 10th the size of a typical monoclonal antibody. Though it is yet to be determined how that a smaller molecule size may benefit a treatment. But that’s something that I’m sure will be explored in the months and years to come.

It’s very gratifying to see that we have a new opportunity, a new molecular structure, a new molecular entity, that could expand our therapeutic options. The specific benefit of having small molecules that remains to be seen. One can always speculate that there may be advantages, but we’re just very early in this process. It’s going to take a little more time and probably a lot more thought in order to really maximize the opportunity that sonelokimab could report.

In a phase 2 trial published in the New England Journal of Medicine, roflumilast, a steroid-free topical PDE4 inhibitor, led to significantly high rates of clear or almost clear skin among patients with psoriasis.

Mark Lebwohl, MD, professor in the department of dermatology and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, discusses the data from the phase 3 trial, which will be published later this year.

What were the results of the trials involving roflumilast?
The results were, you know, clearly dramatically superior to placebo, particularly with the highest dose, 0.3%, and at that dose with those results it appeared to be equivalent to some of the best steroid containing preparations we currently use to treat psoriasis.

And of course the whole advantage of Roflumilast is that it is not a steroid and has none of the steroid side effects that we are concerned about. And the phase three data usually is less effective than the phase two. They went with their top dose 0.3% in a double blind placebo controlled trial, two trials, parallel trials and and those results were actually better than the phase 2 trials.

In the phase two trial, the peak effect was at week 8 in terms of difference to placebo, but at week 12 the numbers were actually even better, particularly for areas like intertriginous areas. We don’t like using steroids on the face, the groin, the armpits, the area under the breasts. The reason that we don’t is that those areas are thin-skinned. They absorb more steward and patients will develop side effects like stretchmarks, which are irreversible in those area.

So in the in that trial, they particularly separated out those areas, and at Week 12 almost the vast majority of patients were clear or almost clear. Most of them were clear, completely clear in exactly those areas which are areas where we don't like to use steroids. So that is one of the advantages of roflumilast cream.

What are the advantages of a cream versus an injected biologic?

You know, the overwhelming majority of patients with psoriasis have limited disease and are not candidates for biologic therapy, the overwhelming majority. Now, it turns out that there are patients who have severe disease and they would do well with the biologic. But many of them still have residual disease. So, when we say patients achieve PASI 75 or PASI 90, that means 75 or 90% of their psoriasis has cleared. But they might still have 10 to 25% they then become very good candidates for topical therapy. So, essentially, topicals are used by everyone. They’re used in patients with biologics, but they will, in the majority of patients who are not candidates for biologics, topicals are the primary treatment modality that is used.

Will roflumilast address an unmet need in patient care?

Very much so. You know, most of the treatments used for steroids now are I mean used for psoriasis now are steroids. And so yet we try to get away without using steroids and that's why drugs like crisaborole are out there. There are not a lot of non-steroids for psoriasis. The two primary ones are calcipotriene and tazarotene. And actually specifically on the intertriginous areas, both of those are quite irritating. So we really needed a non-irritating topical that is not a steroid to use on intertriginous areas and I think roflumilast provides that.

Were there any safety issues in the trials?
 It was a very low rate of irritation, unlike most of the non-steroids that are out there. This had very very little irritation.

I think that right off the bat, my colleagues will not worry about prescribing this. I would say the biggest barrier is going to be access. And I think if the makers of roflumilast can make sure that dermatologists and their patients have access to the treatment it will be used a lot.

Where does the research go from here?

At this point they have to apply to the FDA for approval based on the data. I would hope it would easily get approval and once it hits the market, they've got to figure out how to make sure consumers get access to it.

There’s still a big unmet need in psoriatic arthritis. Again, drugs are coming out that will achieve that better than the drugs we currently have, but there still will be an unmet need you know. And, you know, most patients treated with biologics still have residual disease that we are not yet at a time where we can give somebody an injection and then turn around and say the psoriasis is gone. So there's still room for research in psoriasis, but I will say the systemic therapy market has is somewhat crowded and that need is it's not completely met in that market, but it's getting better and better in topical therapy. There’s still a big void.

Disclosures: Mark Lebwohl receives research funds from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc.

Dr. Lebwohl is also a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitatation of  International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica.

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

In the phase 3 BE VIVID trial, treatment with bimekizumab, an IL-17 inhibitor, resulted in statistically significant improvements in psoriasis compared with ustekinumab.

The study included 567 patients with moderate to severe plaque psoriasis across 11 countries.

Andrew Blauvelt, MD, President of the Oregon Medical Research Center, spoke with MD /alert about the trial and the safety profile of the biologic drug.

What was the idea behind this study?

The new drug here is called bimekizumab, or “bime” for short. It is a new biologic for psoriasis that is in development currently. And for all new drugs they go through the phase 1, phase, 2, phase 3 studies in order to gain FDA approval and this particular study which we also called BE VIVID was one of the pivotal phase 3 studies for bimekizumab that is then going on to be evaluated by the FDA for drug approval. And, in this particular study, the comparisons were placebo for 16 weeks and the drug ustekinumab for 52 weeks.

So, we had some patients on placebo, some on ustekinumab, and some on bimekizumab for 16 weeks.  Those on placebo for the first part then were transferred over to bimekizumab for the rest of the 52 weeks, and those originally on bime and originally on usti stayed on the drug for the entire 52 weeks. So it was to compare this new drug not only with placebo, but with a high quality biologic that's on the market, ustekinumab over the course of one year. 

What were the study findings?

As expected, we can start first with the ustekinumab data, so the primary endpoint is the time in the study where the main analysis takes place, and in this study was week 16, so the primary endpoint, week 16, and the assessment we used was something called a PASI90. And that means the percentage of people who are 90% better or more. So, what percent of people on drugs achieve that level of success?

And in the case of bimekizumab, the number was 85%, that's newer biologic. In the case of ustekinumab it was 50%. So and then we also think of another measurement as being similar to PASI90 and that's the IGA-01 score. That’s being clear or almost clear skin.

And for bimekizumab it was 84% for that measure and it was 53% for ustekinumab. So, the combination of those two measurements at Week 16 really point to the validity of the measurements. They go hand in hand with one another where 84-85% of patients are clear or almost clear with the new drug after 16 weeks and 50 to 53% of the patients treated with used to ustekinumab are clear or almost clear at Week 16. So pretty big difference is about 35% more patients responding to the newer drug. 

What did the long-term data show?

And that kind of takes me into, you know, the second part of this study, and that's the week 52 data. So, I just described to you the initial data. But what happens overtime? You know from Week 16 to Week 52, what happens? And in that is important because as I just said, you need to keep people on drugs and the question is you know, do they stay clear or do you lose the effect over time, which does happen with some drugs that we have. 

So if we look at the week 52 data, we see that PASI90 or that IG 01 it's basically still in the 80s for bimekizumab  and it's still in the 50s for ustekinumab. So that's good news, actually. That's showing that we have retained efficacy or durability of the drug over the course of one year.

What is the safety profile?

Safety is a really important part of any medicines. You know any medicine we use and in particular in psoriasis, where we've seen a lot of misperceptions, both in the patient community and in the dermatology community, and it just kind of amazes me. We still have some of these misconceptions and misperceptions out there because before we had biologic therapy we were dealing with drugs like methotrexate and cyclosporine and acitretin that has significant side effects. With methotrexate and cyclosporine, we’d have to monitor blood tests for either kidney function or liver function. And patients didn’t always tolerate those older pills.

Then we got biologics in the early 2000’s, predominately the TNF class. And they were much better than those drugs. But because of some rare possible or uncommon possible side effects with biologics in the early days, the impression stuck with a lot of people that biologics weren’t safe. And yes, the early ones, that class does have more potential issues compared to the newer biologics. But in general, even TNF blockers, in my view, are much safer than the older drugs we used to use like methotrexate and cyclosporine.

So, what we’ve seen now with these IL-17 and IL-23 blockers, of which these two drugs fall into those two categories, that’s where the new biologics fall. They’re much more targeted to the skin and they are less immunosuppressive if you will to cause, for example susceptibility to internal infections or to cause cancers. So, we really don't see those issues at all with the newer biologics IL-17 and IL-23 blockers.

And that’s exactly what we saw in this trial. We didn't see any increased signal with internal infections, with cancers, with any blood test abnormalities, over the course of a year. So that's really consistent with what we've gotten used to in the last five years with the newer drugs being a particularly safe, a very safe to me. The safest drugs we have now are IL-17 and IL-23 blockers.

Does that mean you know there's never any side effect? No, but I would say the most common thing we saw with bimekizumab was oral thrush or candidiasis. And I mentioned that at the beginning we saw it in about 15% of patients. And most of the cases were mild to moderate, and they were easily treatable. In most cases patients just continued on the drug, on bimekizumab and were able to treat the thrush. So, we didn’t consider those that we don’t consider that a major issue.

Ustekinumab, it’s been out for a long time. Really safe drug in my view. Essentially no issues to worry about. And that’s what we saw in this trial as well.

How have biologics changed psoriasis treatment in the past 20 years and what challenges remain?

If you just look at younger people training now, the TV commercials, millions of people now on biologics, it’s really been a revolution for our field. The big problems we still have are two-fold. One is access. So even though millions of people are on these drugs and the more recent ones are even better than the older ones, they’re still so expensive. And we still have payers putting barriers to the prescriptions so that dermatologists can’t always prescribe them when they do want to use them because of the barriers involved. That’s still a big issue. I see that as possibly changing if we can get cheaper biologics and drop that price or get price wars, or something where they become much more reasonable and they can become more widely used for people that need them. And the second problem, that I alluded to earlier, they’re not cures. So yes that is still a challenge for science and for the future, but I think the insights that we’ve gathered – for example the IL-17, IL-23 pathway that I mention to use is critical. It’s like an Achilles heel pathway for psoriasis. We know that if we block it well we can clear up psoriasis. So what we need to know, I think, is develop strategies to more permanently knock down that Achilles heel, that pathway, so that patients don’t have to stay on shot therapy every few months. So that’s an opportunity in the future. But if you have bad psoriasis and you’re struggling in your life, and you have proper insurance, there’s no reason why you have to life with psoriasis these days. There are so many medicines that can clear up disease in a safe manor. And that’s a big step compared to 20 years ago.


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.