'It’s an Exciting Time for Psoriasis' Transcript

Archie: My name is Archie Franklin and joining me today for a discussion about the latest updates in psoriatic disease management and research from the American Academy of Dermatology's Annual meeting in March is Dr Mona Shahriari, Associate Clinical Professor of Dermatology at Yale University School of Medicine and Co-Founder of Central Connecticut Dermatology, where she is also the Associate Director of Clinical Trials serving as principle investigator and sub-investigator for numerous multi-center clinical studies. Dr Shahriari's clinical and research interests include inflammatory skin conditions with a focus on psoriasis and eczema, and the study of novel therapeutics. She is also a National Psoriasis Foundation Medical Board member and the senior editor of the Journal of Psoriasis and Psoriatic Arthritis, National Psoriasis Foundation, peer reviewed journal for health care providers.

Archie: Welcome Dr. Shahriari. Thank you for being on Psound Bytes™. It's always a pleasure having you on the show.

Dr. Shahriari: Thank you so much for having me.

Archie: Well, we're here today to talk about the 2025 AAD Annual meeting. You facilitated a session addressing real world therapy selection for those of us who live with psoriasis. I heard it was excellent. As part of your presentation, you mentioned the results of head-to-head studies comparing the efficacy of IL-17 and IL-23 inhibitors. My question to you is how important are head-to-head studies and can you share results of the IXORA-R, RADIANT, and Spirit H2H studies with us today?

Dr. Shahriari: Absolutely, Archie. So those are a couple of critical trials in the psoriasis space and the reality is head-to-head studies are the gold standard when it comes to comparing efficacy amongst therapeutics. So they're very important and I'm going to start with Spirit Head-to-Head because from the standpoint of longevity, that's the first study that hit the space amongst the three that you mentioned. But for quite some time we had thought TNF inhibitors were superior to IL-17's when it came to efficacy, for not only psoriasis but also psoriatic arthritis. So to better study this in the Spirit Head-to-Head trial, we did a head-to-head between ixekizumab and adalimumab and they were looking at a novel endpoint. The simultaneous achievement of PASI 100 and ACR50 at Week 24 and what we found was IXE was superior to adalimumab when it came to that joint endpoint of PASI 100 and ACR 50 achievement. But some skeptics may say, well, we know IXE is strong in the skin. How did it do in just the joints? Well, when you take the skin out of the equation, IXE offered joint improvement that rivaled that of adalimumab. So really the take home point from this study was that in the types of patients that I see in clinical practice as a dermatologist who have primarily plaque psoriasis with some joint involvement, you can confidently pick IXE over adalimumab. Now to shift gears a little bit, we knew that the IL-17’s as a class were fast. But when the IL-23’s hit the space, we really didn't know which class was faster. So to better study that IXORA-R was designed, which was a head to head between ixekizumab and guselkumab. And this was actually the first time that an IL-17 challenged an IL-23 to a dual, because historically it was the other way around. And what we were looking at was PASI 100 at week 12 and what we saw was IXE was superior to Gus in the proportion of patients getting to PASI 100 at week 12 with superiority as early as week two. But Gus did catch up by week 24. So what this study really showed us is that in patients in which the speed of response is important, you need to cool down the psoriasis yesterday. You should really reach for IXE over Gus. And lastly, when Bimekizumab hit the space we had this thought process that are all IL-17’s the same? So does it really matter that bime is targeting both IL-17A and F while Secukinumab,  ixekizumab, target only IL-17A. Well, we really didn't know. So to answer this question, the Be RADIANT trial was conducted and that was a head to head between bimekizumab and secukinumab. What we found was bime was superior to secukinumab in the proportion of patients getting to PASI 100 at week 16 with superiority as early as week 4. And what this showed us was that blocking both IL 17A and F does matter to our patients. You get a greater and a faster response and it did help distinguish bimekizumab from its siblings in the IL-17 space. But with great power comes great responsibility, and there was a trade-off. So what we saw in terms of efficacy with bime, we did see also a higher rate of oral candidiasis in these patients in comparison to the patients that were on secukinumab. So this is something that we need to keep in mind when counseling and monitoring patients in the real world.

Archie: But you would say there are good treatments for some of those adverse events, is that correct?

Dr. Shahriari: That is correct. So in the real world, I love to use either topical or oral antifungals, and for the instances where the candidiasis (whether it was oral, genital) has popped up. I've seen very good resolution with no more than a seven day course of an oral antifungal or a topical antifungal.

Archie: That's good to know. In another portion of your presentation, you address treatments for high impact areas such as the scalp, the palms of the hands, and the soles of the feet. What treatment options are better suited for such areas, and does any treatment work faster or better than others? Are there any special considerations such as side effects to keep in mind when choosing a treatment for high impact areas?

Dr. Shahriari: So these high impact areas are really getting a lot of buzz nowadays because what we found is they're particularly challenging to treat, especially with topicals. But also, they're particularly debilitating for patients from a psychosocial as well as a quality of life standpoint. So I tend to have a low threshold to consider systemic therapy in these patients anyways. Now when it comes to scalp psoriasis, which is one of the high impact sites that you mentioned, using both clinical trial data and real world data, we discussed how I pick an IL-17 as my first line agent, followed by an IL-23, followed by either an oral deucravacitinib or an oral JAK inhibitor. Obviously when selecting a therapy, it's important to ensure that it's going to be safe for the patient. So, for example, if I have a patient with uncontrolled inflammatory bowel disease, I'm not going to go to an IL-17. I'm going to start them with an IL-23 in that instance. So, the art of therapy selection really takes the whole patient into account. And one thing to note, when it comes to scalp psoriasis, only guselkumab, secukinumab, and apremilast have scalp psoriasis data in their FDA label. So in patients with lower BSA like less than 10% where insurance approval may be an issue, you can utilize the language in the label for these three drugs to potentially get approval. Now you also mentioned palmar plantar psoriasis. And In my talk I did discuss the hyperkeratotic variety and I do feel there are two groups of patients when we're dealing with the palms and soles. Those that have predominantly palm and sole disease and very little psoriasis elsewhere, and those with moderate to severe plaque psoriasis all over and some palm and sole involvement. I really feel the former is different in terms of its cytokine milieu and tends to be harder to treat and doesn't respond as well to traditional therapy. So for my patients with predominantly palmar plantar hyperkeratosis, we discuss how I actually pick a JAK inhibitor as my first line agent. We have lots of real world data that's come out about the efficacy of this class in these individuals. It works fast. It works well. My second line is an IL-17 or an IL-23, and when we looked at the trial data and real world data, there wasn't much difference between these two biologic groups. And sometimes when I'm really reaching for a Hail Mary, I might even combine a biologic with methotrexate or apremilast if monotherapy is not enough.

Archie: That's terrific to know because so many of my colleagues with psoriasis have struggled with palmar plantar psoriasis. So those are great things that I hope they take away from this podcast today. Other high impact sites were also addressed, such as genital psoriasis and nail psoriasis, which are considered difficult to treat. What's the most effective way to treat such areas and do you have any new treatment strategies to share? 

Dr. Shahriari: Absolutely 'cause those are two other areas that I think we both agree that can have a high impact on patients. When it comes to nail psoriasis, I personally like the IL-17’s as a first line with Bimekizumab really being my preferred and then my next line is going to be a TNF inhibitor, so more of a second line agent. But it's really important to also screen these patients for psoriatic arthritis because nail psoriasis is actually an independent risk factor for psoriatic arthritis and I always want to ensure that whatever therapy I choose protects the joints. Now, genital psoriasis is another one that you mentioned, and it's a condition with the low BSA, but a significant impact on patients from a psychosocial standpoint and even the ability to have intimate relationships. And given that limited BSA, sometimes topicals can be an option. I actually like topical tapinarof or roflumilast, especially in these areas for patients that aren't ready to go to a systemic. But in general, I do have that low threshold to go to a systemic agent and IL-17’s are my first line in particular ixekizumab since it does have the genital psoriasis on the label. But the bottom line is really in patients with psoriasis in low BSA but high impact areas, we as clinicians need to understand that the skin doesn't tell the whole story. There is a multidimensional burden of disease beyond what we can see that impacts our patients and we need to keep that in mind and have a low threshold to escalate therapy to more advanced therapeutics in an appropriate fashion.

Archie: Thanks so much for that cause I've met again colleagues going into their clinician for mainly nail psoriatic disease and it wasn't till three years later they finally got diagnosed realizing it was psoriasis and psoriatic arthritis. But the challenges they were losing their nails and things were so difficult for them. It's so glad to hear that there's a great sequencing, if you will, to be able to handle that particular disease. A type of psoriasis that is difficult to treat is generalized pustular psoriasis or GPP. I've heard spesolimab, an IL-36 inhibitor, is the only FDA approved treatment for GPP. Why is GPP so difficult to treat, and are there any other treatments in development for GPP?

Dr. Shahriari: So Archie, you're absolutely right. GPP is a different beast in this psoriasis realm. For starters, from a pathophys standpoint, we're used to plaque psoriasis, which is largely driven by IL-17 and IL-23 pathways. But GPP is actually driven by dysregulation of the IL-36 pathway and that's why traditional biologics don't tend to be as effective. These patients are also sicker. They can sometimes present with fever, malaise, leukocytosis, elevated, inflammatory markers. They can go from zero to 60 pretty rapidly, making it a derm emergency in some instances. And they can also have chronic comorbidities like cardiovascular disease, psoriatic arthritis and even diabetes. And it can be really tough to treat because the flares are unpredictable. They're also recurrent and they can be very severe, making long term management complicated. And like I mentioned before, traditional biologics may not work as well or they may not work quickly enough to calm down the flare. And all of this is going to lead to impaired quality of life in our patients that are living with this unpredictable disease. When it comes to therapy, spesolimab has really been a game changer in this space with patients seeing significant improvement in their flares within a week of starting therapy. There are other therapies in development for not only flare management but also maintenance regimens with promising data like imsidolimab. Cyclosporine still remains a reliable traditional systemic that's used for acute flares or bridge therapy. But nowadays, with the advent of spesolimab, long term use is not something I do because of safety concerns. So I tend to favor the biologic agent over the oral cyclosporine.

Archie: Is it difficult as far as the challenge of diagnosis too? I could easily see this kind of disease looking like maybe mycosis fungoides or some type of cutaneous lymphoma or something like that?

Dr. Shahriari: Well, it has many different faces, so one of the I think top things that gets diagnosed as is a type of drug rash called AGEP. And many times these patients because they present to an emergency room setting depending on the ER if you don't have dermatology on board, if they don't proceed with a biopsy, these patients can be misdiagnosed and remain undiagnosed for years to come. I still remember a patient of mine that was misdiagnosed. I got a call. I decided to start the patient on cyclosporine. Now this is before we had spesolimab, and the rheumatologist that was actually also consulting on the patient said “no, this is not GPP. The dermatologist is wrong and stop the cyclosporine”. So the patient continued to flare. So then a week later, they consulted me again and I'm like you guys didn't start the cyclosporine? And so I came back and I'm like alright, we need to take ownership of this as dermatology. And when we started the cyclosporine the patient cleared up really rapidly and this is the perfect example of a time that not only was there that misdiagnosis but there was a correct diagnosis and other people because they didn't agree, they took that away from the patient.

Archie: That's so challenging. I mean, I know you have to deal with that I'm sure regularly as you work as a team with your clinicians and things like that. Speaking of team I know you have a colleague, Dr. Bruce Strober, who's the President of the International Psoriasis Council and he discussed the GUIDE study, which highlighted the use of guselkumab, an IL-23 inhibitor as the early intervention for onset of psoriasis. Can you please share some of the results of the GUIDE study and how efficacious guselkumab is in possibly delaying psoriasis?

Dr. Shahriari: The GUIDE study is actually really exciting development in the field of psoriasis therapy because our researchers want to see what happens if you treat patients early. When their psoriasis is still relatively limited, could you alter the disease course? That was really the premise of the study. And this was thinking of disease modification and is that even possible for these patients? And what we found was that in patients with shorter disease duration two years or less who received Gus, they had higher rates of skin clearance like PASI 90, PASI 100 and it makes us wonder if early IL-23 blockade can influence that immune memory that's responsible for disease persistence and flares and what we’re still studying is can this even prevent disease progression to psoriatic arthritis. So the key take home point is that we need to do a better job of diagnosing our psoriasis patients early and commencing therapy so we can optimize outcomes for our patients.

Archie: You mentioned the resident memory cells that were impacted here and they are actually helping and reduce future flares. Or do you think they do actually help that in this particular point?

Dr. Shahriari: I think it does because the longer we have those cycles of inflammation happening, the more of those memory cells that are gonna accumulate in the same area. And that's why we tend to get flares back always in the same area. But over time, as we are potentially impacting the ability of these T cells to launch a reaction, we can have less memory T cells that are waiting there basically in wait for the trigger that brings on the psoriasis and so if a trigger does happen, these patients are less likely to develop a full blown reaction.

Archie: That's terrific. Very interesting too. The GUIDE study was around the use of IL-23's. Are they looking at some of the others as far as early intervention with the IL-17’s or those kind of things?

Dr. Shahriari: So I think what a big push has been currently is we really want to do disease modification and help treat our patients earlier. Are there specific studies in the works? Not that I know of, but they are thinking about coming up with studies that can really look at this early intervention cause some of those drugs that you're mentioning, they are still undergoing their pivotal phase three trials. And so we still don't know for sure if they're going to go down the road of those sorts of studies through the actual company.

Archie: So given that, would you say that IL-23 is the master cytokine associated with psoriatic disease?

Dr. Shahriari: Yeah. Now whether IL-23 is the master cytokine, it's something that we can definitely debate. But what's indisputable is that IL-23 does play a key role in the development of the signs and symptoms of plaque psoriasis, and in particular it plays a role in that TH17 differentiation and expansion and leads to IL-17 production, which then goes to the joints, goes to the skin, and leads to the signs and symptoms of psoriatic disease. And that's why I think targeting IL-23 is really effective at reducing or even eradicating the signs and symptoms of psoriasis.

Archie: In keeping with discussion of the treatment for psoriasis were any new pathways or upcoming treatments presented? I know there's an oral IL-23 in development, icotrokinra, and another TYK2 inhibitor. Any additional treatments you mentioned that offer more personalized and targeted approach?

Dr. Shahriari: Yeah. So there's a lot of excitement around icotrokinra, the oral IL-23. Now this medication, dare I say, looks like it has biologic like efficacy and a favorable safety profile. And it's a sign that the gap between the biologics and orals with respect to efficacy is starting to narrow.  So our patients can finally have a choice in terms of picking the drug that's most convenient for their lifestyle. And that's going to differ from patient to patient but it'll be nice to be able to give patients this option and really personalize the approach to therapy.

Archie: There was a data presentation for several TYK2 inhibitors. Does this therapeutic class of medication offer a more specialized or targeted approach?

Dr. Shahriari: So I have to say the TYK’s were the talk of the town and there were two next generation TYK2 inhibitors on this horizon for the treatment of plaque psoriasis with Zasocitinib and ESK-001 that are looking very promising in terms of their efficacy and safety. And I'm really eagerly waiting on phase 3 data to get a better feel for how these drugs will compare with our currently approved FDA oral therapies. But also these oral agents through efficacy in psoriatic arthritis is something I'm curious about as a dermatologist, cause again my goal in life is to make sure I'm protecting the joints and ensuring that there is no advanced progression over time. Now in that TYK class, there was one more with very early results out of China that looked extremely promising. We're talking high levels of biologic efficacy in a pill, but there's only so much you can gather from a phase 2 study. I find most drugs, their phase 3, which is larger numbers, isn't as good as their phase 2. But I'm optimistic about what this new class will bring. And again, having oral options that are comparable in terms of efficacy to biologics, is really going to allow patients to pick their own adventure, so to speak.

Archie: Yeah, I understand. And if TYK’s were the talk of the town, I'm sure their hot topic had to be, at least for the last few years, has to do with the GLP-1 medications, 'cause we know obesity and the associated inflammation can impact the severity of psoriasis and response to treatment. In your opinion, how helpful do you believe the GLP-1 medications could be as an adjunct therapy for people with psoriasis? And when do you consider the use of such therapies?

Dr. Shahriari: So I completely agree with you. The GLP-1’s have the potential to do a lot of good for patients with inflammatory skin disease and not just psoriasis. We're talking about the whole space. But I'm going to focus on psoriasis here since that's our conversation. But just some background information. The GLP receptor agonist, they’re a class of meds that were originally developed for Type 2 diabetes. But now they're being widely used for weight management, and the examples are semaglutide, tirzepatide being 2 examples of drugs that are out there in the sphere. And when it comes to treating inflammatory skin disease, we have to remember, adipose tissue isn't just fat. It's metabolically active and it secretes pro-inflammatory cytokines that may worsen psoriasis severity. Obesity is linked to poor response to biologics. We know this, in particular our TNF inhibitors. And we know that weight loss, even the most modest weight loss can improve psoriasis severity and increase biologic efficacy. So with GLP-1's we have the potential to get a sustained medically supervised weight loss at levels that are hard to achieve with lifestyle modification on its own. On top of that, the GLP-1’s can have anti-inflammatory effects and even offer a protective effect when it comes to cardiovascular risk, making them a great adjunct to patients who have plaque psoriasis, given the associated comorbidities of the disease. And really, in my opinion the GLP-1’s can be helpful in those select patients with psoriasis whose BMI might be 30 or 27 or higher with comorbidities or difficult to control psoriasis, or those that are showing suboptimal response to biologic therapy. And I've actually started prescribing these in my clinical practice. And if you don't feel comfortable, that's OK you can have a PCP or an endocrinologist prescribe it as well. But I do think this is a great adjunct and for patients, they need to really be asking their doctors about this because it can definitely change their management as a whole.

Archie: I appreciate that knowledge because I've always had some obesity issues, but I'll use this time to talk about a colleague who's been on GLP-1’s and has lost over 120 lbs and is just feeling a lot better and  very successful. So

Dr. Shahriari: Wow.

Archie: So glad to hear there's something like that going on. I noticed there were a few sessions I should say, addressing cardiovascular disease and psoriasis. Can you provide an update regarding the impact of cardiovascular disease in relation to psoriasis?

Dr. Shahriari: Of course. And I think this is something that we've been talking about for a lot of years, and we know the systemic inflammation in psoriasis does drive cardio metabolic risk. Dr. Joel Gelfand has really been a trendsetter in this space with his long standing research that's emphasized that for every 10% increase in body surface area affected by the psoriasis, there's a 20% increase in the risk of major adverse cardiovascular events. So it really makes sense. The higher the inflammatory burden, the higher the cardiovascular risk. And interestingly severe psoriasis is comparable in risk level to traditional risk factors like diabetes when it comes to cardiovascular disease. This is why it's so important to be screening patients for their cardiometabolic risk factors in derm clinics. In my clinic I always ensure my patients have a primary care - they're getting their blood pressures, liver function tests, lipids, sugars, kidney function, all checked yearly. And as derms, we need to keep the whole patient in mind and remember the impact of psoriasis goes beyond what we see on the skin and we need to take that holistic approach to therapy to optimize outcomes for patients.

Archie: Thanks so much for that. Depression, another comorbidity of psoriasis, was addressed by Dr. April Armstrong, a member of the National Psoriasis Foundation Medical Board and the former chair. Dr. Armstrong presented data about treatments for psoriasis that show a notable reduction in depression scores. Can you please address the study and how important is this as far as the research goes?

Dr. Shahriari: Well, this is very important because the unique thing about the skin is a lot of patients with skin disease, they can see their disease. So they do have a significant psychosocial impact, whether it's depression, anxiety that comes from just seeing the disease that they're living with, not being able to cover it up. It's different than having high blood pressure or diabetes, which you can't necessarily see, but you're kind of struggling with on the inside. And the data that Dr. Armstrong presented really showed that patients that are undergoing treatment, through IL-17, IL-23 inhibitors, do report a notable decrease in their depression scores that indicates these drugs have benefits beyond just skin clearance. And this data underscores the importance of including a mental health screen as part of any psoriasis patient’s visit. I usually tell my patients that “having psoriasis can sometimes make us feel down or anxious. Do you ever feel like that?” It can be more unassuming to ask it that way and really welcome an open conversation. But screening for depression can really help guide treatment decisions. And in someone who's struggling with the mental health burden of disease, I do have a lower threshold to go to a systemic and clear the disease more quickly because I do think that's going to improve what they see on their skin and then their overall mental health.

Archie: It's great to hear your clinic is leading edge and making sure that gets done. And so from a patient's perspective, the 2025 AAD highlights a promising future managing the symptoms of comorbidities of psoriatic disease. What was the most exciting topic for you at AAD’s Annual meeting in 2025?

Dr. Shahriari:  Well, as an inflammatory skin disease enthusiast, it's hard to pick just one highlight from AAD 2025 'cause there was just such an explosion of groundbreaking data. But what really stood out was the shift toward early intervention, disrupting that immune memory and dialing in on pathway precision. Because now it's an exciting time. We're not just managing chronic disease. We're reimagining its trajectory. If we treat early, can we modify the disease and prevent progression? Can we change the immune system's memory so the next time a trigger comes about, your immune system isn't going to just jump on it? Maybe it'll take a second for it to process the insult. And also, can we find the perfect drug for each patient? Kind of like a Match.com for patient care. So there's a lot coming down the pipeline that I think is going to be very exciting.

Archie: Do you think that'll include some of the companion testing to make sure we know. I love the pathway precision discussion that you bring about there. I think that’s far more realistic than maybe the idea of sequencing. And do you think we’ll ever get close to where we can get data from a companion test?

Dr. Shahriari: I think that's the dream and we're definitely working on that. I have some my colleagues down at Yale that are looking at pathway precision for atopic dermatitis. The reality is everyone's immune system and their cytokine storm is different. So none of our tests are perfect and ready for prime time yet. But I think with time we're getting better at understanding the underlying pathophys of these different diseases. So that then we can better understand which cytokine storms are playing a role in each patient so that we can pick “you know what, this is the class of drugs you start with. This is going to be your number two” and that will take some of the guesswork out of this process because sometimes it is trial and error.

Archie: That's great. I mean, although maybe not a cure, but certainly continuing to improve treatment is an awesome opportunity at least for me as a patient, and I'm sure you as a clinician to be part of. Thank you, Dr. Shahriari, for providing such interesting highlights from the recent AAD meeting. It's exciting to hear about the latest research and advances being made on behalf of people like me who have psoriasis. Do you have any final comments that you'd like to share with our listeners today?

Dr. Shahriari: So I just wanna say it's an exciting time to have psoriasis. I'm lucky that in my career we had the biologics, but if you think about 20, 25 years ago, we didn't have a lot of options to treat psoriasis with and now we have a toolbox with several more drugs on the horizon. And my hope is that with so many new options and us taking a step towards personalized medicine, matching each patient with their perfect therapeutic, patients can start to live their best life. Free from the constant reminder of their psoriatic disease.

Archie: A day, I look forward to. Thank you so much for your time and look forward to speaking with you again and maybe seeing you at a meeting somewhere.

Dr. Shahriari: Thank you so much. It's been a pleasure Archie.

Archie: Thank you again Dr. Shahriari for discussing what the future holds and the exciting directions research is exploring. The new treatment options sound exciting. For our listeners, you can stay up to date on the latest information by subscribing to the National Psoriasis Foundation Online e-newsletter Advance at psoriasis.org/subscribe. If the content in today's episode will be of interest to someone you know, please share the episode link. And finally, thank you for listening to Psound Bytes™.