Psoriasis Podcast

Biologics in Psoriasis: A Spectacular Run

Steven R. Feldman, MD, PhD; Craig Leonardi, MD


August 03, 2022

This transcript has been edited for clarity.

Steven R. Feldman, MD: Welcome to Medscape InDiscussion on psoriasis. I'm your host, Dr Steve Feldman. Today, we'll be discussing biologic therapy options for psoriasis with one of the pioneers of the field. Although in private practice, our guest published more than 100 research articles in journals such as the Journal of the American Academy of Dermatology, British Journal of Dermatology, JAMA, The New England Journal of Medicine, and The Lancet. I don't know anyone who has contributed more to our understanding of how to treat psoriasis with biologics. It's a pleasure to present Dr Craig Leonardi. Welcome, Craig.

Craig Leonardi, MD: Thank you for that kind introduction and those kind words.

Feldman: You have such a great sense of humor. Do you want to start with some funny story that relates to psoriasis?

Leonardi: Well, I have one story. It involves the global launch of the biologic drug ustekinumab at the World Congress of Dermatology in Buenos Aires. I think the space was about the size of four football fields. I've never seen anything like it. And I'm already starting to sweat because this is the biggest audience I've ever addressed. And the space is full. It's bumper to bumper. I get up on the stage and I'm walking over to the podium and the first thing I notice is this rat's nest of wires behind the podium. It's like you're on a skateboard, but it's on wires and nothing is solid. I'm worried that I'm going to fall over. I have no idea how this is going to turn out. And then a voice from behind me said kind of loudly, "The mouse doesn't work." I had a vagal reaction. My mouth went instantly dry and I figured, okay, I'm going to have to just work my way through the slide deck. They did get their drug approved, so that was a good thing. But that's a harrowing moment in front of so many people.

Feldman: So many people — because at the time, biologics were new and exciting, and now they are such a part of our psoriasis management that it's probably hard to get two or three people to come out to hear a talk about them. We've been using them, what, 20 years? More, maybe.

Leonardi: Twenty years. Yeah. And it's been a spectacular run. Now, when I describe the phenomenon of these drugs being launched into dermatology, I say that dermatologists were sitting around behind their desks with their feet up and then, kaboom — a bunch of stuff fell out of the sky and landed in our laps. It changed a lot of things in our specialty; we pay a lot more attention to statistics and scientific design and all those good things. It was some hard science and lots of fun.

Feldman: So now, when would you think about using a biologic for somebody with moderate to severe psoriasis?

Leonardi: That's a patient who deserves our best drugs. My mission is to put as many patients as I can on these drugs. I have adopted that attitude for quite a while, and it'll offend some people who feel there's not enough consideration and due diligence to the economics of the whole thing. But when it comes to efficacy and safety, these drugs are unsurpassed.

Feldman: Are there any danger issues we should be thinking about when prescribing them?

Leonardi: I have quite a few patients with internal malignancies who are now on biologics for treating their psoriasis. It doesn't always work out, but I've had some great conversations with a survivor and their family, and some of the nicest comments ever made to me were about taking care of them. They said, "Nobody else would touch [treating the psoriasis]. And you made a huge difference in the quality of his life for the last 4 years." That's an intense thing to hear.

Feldman: Especially when we can fix suffering the way we can. So for the patient with cancer, I'm thinking I would lean toward an IL-23 drug first maybe, or an IL-17, and not give them a tumor necrosis factor (TNF) inhibitor.

Leonardi: I think you're absolutely right. TNF antagonists are a bit noisy when it comes to safety. We'd like to avoid all of that if we can.

Feldman: I think it's all relative. When I was just using methotrexate and cyclosporine, I did not think TNF inhibitors were noisy for safety. Now that I have IL-17 and IL-23 drugs, I think they're relatively noisy.

Leonardi: That's right. And that's a natural evolution in our specialty. It's just spectacular.

Feldman: So if I had a patient who I suspected had inflammatory bowel disease, then I might think a TNF inhibitor or an IL-23 drug would be a better choice than an IL-17 drug.

Leonardi: Yeah. I have patients who have inflammatory bowel diseases, but they've also cycled through all the available biologic drugs, and some of them multiple times. I put them on an IL-17 antagonist with the full knowledge and understanding that there's some additional risk. I've got three or four patients like this and it's going well.

Feldman: I'm not so worried about patients who fail treatments anymore because I've got 12 different treatments. But after they fail four, five, or six drugs, I start to wonder if I should have them on methotrexate, too. I don't like methotrexate, but the rheumatologists have been using it for rheumatoid arthritis with TNF inhibitors for a long time. Are you using biologics with methotrexate for patients who tend to develop antibodies?

Leonardi: Yeah, I definitely do that. And at any one time, I've got a couple of hundred patients on methotrexate just for that kind of problem.

Feldman: You know, I think sometimes companies will investigate their drug for a particular niche, whether it be the scalp or the palm and soles. Do you think there are niches where a particular biologic should be used?

Leonardi: Once you're in the class of drugs, I think they're all working roughly the same. I really don't think that drug X is going to be superior in treating scalp psoriasis, and it's going to be bad in treating nail psoriasis.

Feldman: So for the patient who has bad psoriasis, you're going to give them a biologic, but what if they also have joint pain? Do you modify your choice of the biologic?

Leonardi: Yes. I always try to get a TNF antagonist on board with methotrexate. It's something the rheumatology folks have taught me, and I'm willing to go down that path.

Feldman: Yeah, I think the IL-17 drugs are also approved for preventing the progression of diseases affecting joints.

Leonardi: Well, this is really interesting because when you look at the performance of the IL-17 drugs, there were a few trials where they're kind of head to head with a TNF antagonist; for example, adalimumab and ixekizumab. When you put those two next to each other, they're functioning at about the same level in terms of efficacy definitely, and safety.

Feldman: For the joints — it's a similar efficacy for the joints?

Leonardi: [Yes], or using it on the joints.

Feldman: When you have somebody who has really bad psoriasis, they're suffering, they've got extensive lesions, they're red, they're cracked, and they're sore. What do you think of the idea of starting with the safest thing first — maybe a little topical therapy? Try a couple of different topicals first, and then we'll move up to something maybe a little bit stronger, maybe an oral, or maybe some phototherapy before we jump into the more effective agent. What do you think about that as a general philosophy?

Leonardi: You're spending a lot of time and effort and not gaining much for the patient. It's the patient on the end of that. They're waiting for a new treatment, especially in this day and age. I don't like spending any time. I just don't like doing that. I don't want to wait. I want to see the results. And for example, Steve, using an old-school drug, triamcinolone, 0.1% cream — I give them a pound jar of it, and I say to just use it. Just use it, and we'll modify your use of it in another couple of weeks when your other treatments start to catch up.

Feldman: As a general rule, this idea of go slow and be safe first — it's actually a different philosophy that may be much better for patients suffering from psoriasis: Go big. Get the disease under control fast, and then you can always taper down on therapy later.

Leonardi: Absolutely. I'm with you all the way on that sentiment.

Feldman: Well, you taught me that.

Leonardi: For the doctor who doesn't have as much experience as you do — and that's everybody — the dermatologist who is not frequently prescribing biologics, or even the family physician who's not using biologics for psoriasis frequently, what would you suggest they do?

Leonardi: They have to learn how to do this. Unfortunately, it's difficult to run training sessions and educational sessions.

Feldman: I think the rate-limiting step is whether they have a nurse who knows how to get the prior authorization done. If they've got that, should they start patients on a biologic or should they refer to somebody like you or me? Get the patient started and then maybe they can do the follow-ups?

Leonardi: There's a story I have about a doctor who came over to my practice to hang out for the day. I was really impressed that this doctor was having a hard time learning how to treat patients and getting them onboarded. So he came over from 2 hours away. He hung out all day long and then said, "You guys are doing this very differently." I asked how it was different. He said that what he used to do is give patients a prescription and tell them to go see their pharmacist and their insurance agent. He said "insurance agent." He said that. I said, "Wow, was there a car accident along the way? What happened?" You know, those were his thoughts about how to do it. He's never going to be able to experience lots of patients who are on these drugs. But he's aware of them, and he tried, and that's good.

Feldman: You know, I went to one meeting where a top psoriasis specialist was talking about how he monitors patients on biologics. This was pretty early on, so he may have changed. I remember him saying that whenever he put anybody on a drug that affects their immune system, he did a panel of laboratory work, including a CBC, complete metabolic profile, urinalysis, chest x-ray, ANA, CRP, lipid panel, hepatitis panel and an HIV test, and he repeated them at appropriate intervals. And he said I should, too, because I might find something. If you do all that laboratory work, you are undoubtedly going to get false positive tests. What kind of monitoring do you do for these patients?

Leonardi: A little bit more initially, because I don't know the medical history of a lot of patients. We take the history, but then there are other things. So we get a hepatitis B, hepatitis C, HIV test, and also a tuberculosis (TB) test, a complete metabolic profile, and a CBC. All I'm doing with these labs is sniffing for some trouble. That's all. And the next set of labs is going to be in a year, and it's going to be a CBC, a TB test as mandated by our insurance industry, and a metabolic profile. And that's it. I tell my patients that we're going to be doing these tests. I say that if they have a positive result on any of them, we really want to know about it as soon as possible and resolve the result.

Feldman: Fair enough. At some point, either a new medication or a new biologic may not work for everybody. It may not work from the beginning, or it may stop working. When do you decide to switch?

Leonardi: I think a drug should have a pretty decent run. I would say that's at least 3 months. A lot of times, I’ll start combining methotrexate with a drug that's got an inadequate response. And I might go for another month. They're already on a second drug at that time, and then at that point, we'll pull the trigger and move the patient on to a drug with a different mechanism of action.

Feldman: Do you see any barriers to the use of biologics, financially, or just to how patients use them?

Leonardi: Yeah. Let me tell you a sad story. This happened just this week. I had a patient who had worked his way through the prior authorization procedure, and he was up and running on ixekizumab for about 4 months. And then he started to notice that the bill was going up almost exponentially, and the guy was scared out of his mind that they were going to come for the money. So he stopped coming, and he stopped receiving the drug, and he didn't tell anybody because he was scared. It's an incredibly sad story. And we had to tell him, "No, no, if you have a problem, you come here. Come to the office because we've already seen this problem probably three dozen times, and we'll work to get it sorted out. But you have got to let us know."

Feldman: So well said. I can remember patients saying they didn't come in because they've been uninsured. I say, "You're uninsured? That makes you the easiest patient. Great. No insurance company telling me what to do." Any last things you want to pass on to our listeners?

Leonardi: I'll just say, as we wrap up, that what's going on in dermatology with psoriasis is very real. These are real drugs with amazing results. There has never been a time when dermatology was so much in the in the sunlight. Our patients are getting the best treatments, and we're plugged in with wild therapies that are safe, easy to use, and clinically relevant.

Feldman: Craig, I'm going to summarize what I think are key takeaways for our listeners. First of all, as you've eloquently said, our patients with moderate to severe psoriasis are suffering terribly. They deserve to be treated and to get the disease under really good control. We've got these IL-17 and IL-23 drugs that are safer than the TNF inhibitors, which were safer than the oral therapies we used to use. You've got to be able to get patients on them, so you have to run through the prior authorization process. The amount of laboratory monitoring you can do sort of depends on your comfort level. For the follow-ups, you really don't have to do a lot. The insurers make you do an annual TB test. If you want to do a CBC or something after that, you could. If the drug stops working or starts to slow in how it's working, you might add methotrexate, but if it completely stops, it's time to move on to something else. And you don't have to leave people untreated; if their first biologic is stopped, you could start that next one right away and then give it, you know, for 3 months to see if it's working. If it's not working, it's time to move on yet again to something else.

Feldman: Craig, thank you so much for sharing your wisdom with us. I'm Dr Steve Feldman, and this has been Medscape InDiscussion on psoriasis.


Joint AAD-NPF Guidelines of Care for the Management and Treatment of Psoriasis With Biologics

Efficacy and Safety of Biologics for Psoriasis and Psoriatic Arthritis and Their Impact on Comorbidities: A Literature Review

Biologic Treatments of Psoriasis: An Update for the Clinician

Biologic Treatment for Psoriasis in Cancer Patients: Should They Still Be Considered Forbidden?

Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis With Comorbid Conditions and Special Populations: A Review

Inflammatory Bowel Disease in Patients With Psoriasis Treated With Interleukin-17 Inhibitors

Are Biologics Combined With Methotrexate Better Than Biologics Monotherapy in Psoriasis and Psoriatic Arthritis: A Meta-analysis of Randomized Controlled Trials

Comparing the Efficacy and Tolerability of Biologic Therapies in Psoriasis: An Updated Network Meta-analysis

Scalp Psoriasis: A Literature Review of Effective Therapies and Updated Recommendations for Practical Management

Nail Psoriasis: Treatment Options and Management Strategies in Special Patient Populations

Comparative Persistence on Methotrexate and TNF Inhibitors in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Interleukin-17 and Interleukin-23: A Narrative Review of Mechanisms of Action in Psoriasis and Associated Comorbidities

Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients With Active Psoriatic Arthritis and Moderate-to-Severe Psoriasis: 52-Week Results From the Randomised Spirit-H2H Trial

Joint AAD–NPF Guidelines of Care for the Management and Treatment of Psoriasis With Topical Therapy and Alternative Medicine Modalities for Psoriasis Severity Measures

A Survey of Community Dermatologists Reveals the Unnecessary Impact of Trial-and-Error Behavior on the Psoriasis Biologic Treatment Paradigm

Monitoring Biologic Therapy in Psoriasis: A Primer

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