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Steven R. Feldman, MD, PhD: Welcome to Medscape InDiscussion: Psoriasis. I'm your host, Dr Steve Feldman. In this fourth episode of our second season, we'll focus on oral psoriasis treatments. Who benefits most from taking oral agents? And what are the advantages and disadvantages, if any? Our guest is the current president of the Society of Dermatology Nurse Practitioners and a member of the National Psoriasis Foundation's Emeritus Medical Advisory Board. She's a practicing dermatology nurse practitioner who has published and coauthored articles on the management of patients with psoriatic disease. Welcome, Lakshi Aldridge.
Lakshi M. Aldredge, MSN, ANP-BC, DCNP: Thank you. Dr Feldman. I'm delighted to be here.
Feldman: Lakshi, how did you decide to focus on dermatology as a specialty?
Aldredge: I've worked at the Portland VA in Oregon for the past 32 years. When I started in dermatology, I was fortunate to work with many residents and one of my mentors, Dr Andrew Blauvelt, who is passionate about caring for patients with psoriasis. Under his tutelage, I fell in love with psoriatic disease and the patients who suffer from this horrible disease. From that point forward, I decided that would be my path, and I've enjoyed caring for patients with psoriasis and psoriatic arthritis, as well as the evolution of treatment options we have had for the past 22 years.
Feldman: What a great way to start — with Dr Andy Blauvelt. If I wanted to know something about psoriasis, he'd be somebody I'd go to.
Aldredge: I was very fortunate, yes.
Feldman: Yes. And you've been doing this for 20-something years?
Aldredge: Yes. I do not want to age myself, but back in the day, we were just beginning to introduce the biologic therapies. We've come such a long way, and I'm excited to talk with you more about some of our newer treatment options.
Feldman: You're a nurse practitioner. You have so much experience managing patients with psoriasis. I assume you're at least as good at it as I am. What generally is the role of a nurse practitioner in managing patients with psoriasis or other conditions?
Aldredge: That's a great question, and I'm often asked what the role is of nurse practitioners and even physician assistants who are in the dermatology clinic managing psoriasis. We are part of the dermatology care team. There are many different settings where psoriasis patients are seen and treated. It may be in a private practice clinic, it may be in a university setting, or it may be in a public health clinic. In all these settings, there's a wide variety of what we call "derm teams." It may be a physician-led team. It may include a nurse practitioner or a physician assistant. I embrace and endorse the concept that the most successful management of any dermatology patient — especially those with complex, chronic cutaneous disorders — is best managed by a derm team. For me, by working in an environment in which I became comfortable under the guidance of a collaborating physician and another expert in psoriasis, I gained confidence. The physician allowed me to practice independently as I gained confidence and felt comfortable caring for patients, and he was able to see my management technique. But as I said, it's been a 20-year journey. Every nurse practitioner and physician assistant is different. We have a need in the field of dermatology to have providers seeing patients. We know there's a great access issue. In the management of psoriasis, a team-based approach benefits the patient the most, and nurse practitioners are an important and integral part of that team. Certainly, with the right teaching, the right understanding, and the right confidence, nurse practitioners can comfortably care for patients once they gain that education.
Feldman: I imagine the rules vary from state to state, but maybe some states allow nurse practitioners to basically practice independently. Even in situations in which physician extenders are part of the team, it seems like a lot of the time nurse practitioners are practicing, for all practical purposes, nearly if not completely independently. That doesn't bother me because in my experience, the physician extenders with whom I've worked have been fabulous professionals. What's your sense about the concern some physicians have with the independence of nurse practitioners?
Aldredge: On the forefront of the American Medical Association and certainly the American Academy of Dermatology is this concept of nonphysicians caring for patients and setting up independent practices. In almost all states now, nurse practitioners can practice independently based on their scope of training, education, and competencies. In the state of Oregon, we have practiced independently for many years; in fact, we were one of the first states. What's important to understand is that the role of nurse practitioners has evolved from the military and a need for care, and it expanded to rural communities where patients had a difficult time getting into medical clinics or coming into the city. So, it was born out of a need for patients to receive medical care. There are few nurse practitioners who truly practice independently in the United States. Most of those nurse practitioners gained their education and training in formal training programs.
We have three dermatology nurse practitioner fellowship training programs that are 1-year long. They have also studied as nurses for 4 years and then as nurse practitioners for an additional 3-4 years. That's eight-plus years, plus then an additional year of training within the dermatology specialty. So, there is a rich amount of education behind dermatology nurse practitioners. But most nurse practitioners are practicing within a collaborative practice under a team model. What is important to understand is that with chronic conditions such as psoriasis and atopic dermatitis, in the United States today, most of these patients are being cared for by nurse practitioners and physician assistants regardless of whether they're practicing independently. By far, the majority are within a collaborative practice in a setting with physicians, nurses, Mohs surgeons, and other nurse practitioners and physician assistants as well. That's a model that works well. But I know that in communities of need, such as rural areas, it's difficult to recruit dermatologists to those areas. Nurse practitioners have filled an important and integral need in these places.
Feldman: Excellent. Let's move on to the topic of the day, which is the use of oral agents. Which patients with psoriasis are eligible for oral treatment?
Aldredge: This is a critical question, and I think it was Dr Krueger who taught me that we moved away from treating patients according to their severity, right? Traditionally, we had patients with mild, moderate, and severe disease. The idea was to treat patients with mild and localized disease with topicals. If they had moderate disease, you would consider oral agents. If they had more severe disease, we would move right to the biologics. But that paradigm has shifted. It involves looking at whether the patient sitting in front of you is a candidate — if they have localized disease and topicals are appropriate, or if they need to move to systemic treatment regardless of the body surface area involved.
When we look at the systemic management of psoriasis, we have oral agents and we have the biologic therapies. Within that oral spectrum, we have the traditional oral agents, such as methotrexate, cyclosporine, and acitretin. Now, we have some new additions to that armamentarium, including the TYK2 (tyrosine kinase 2) inhibitor that has come along and the PDE4 (phosphodiesterase-4) inhibitor that's been around for a while, which really do increase the palette from which we can draw. When I'm looking at a patient who is a candidate for systemic therapy and thinking about the oral agents, there are a couple of considerations. First, what are the patient's comorbidities that may affect my selection choice? Unfortunately, we also must think about their financial situation. Do they have insurance coverage? If not, that may take certain medications off the table for me. I will tell you, especially working within the VA system, methotrexate has been a go-to treatment for a very long time. It works well, and it's a great starting point for a lot of patients. But I believe in very individualized therapy. So before, when we would have an algorithm, you would start a patient on topical therapy, perhaps phototherapy, and then go to methotrexate. Those are step therapies that have gone by the wayside. The patient sitting in front of you has specific needs. They're also very sophisticated, thanks to direct-to-consumer advertising, about their knowledge of therapies available and what they want that will fit in with their lifestyle.
Feldman: It seems like lumping these things together as oral agents has certain limitations since methotrexate is so different from, say, apremilast. What are some of the things you think about when you're starting these oral agents?
Aldredge: Absolutely. Cyclosporine has been around forever. In fact, it's one of the first ways we identified that psoriasis was an immune-mediated disease. We use cyclosporine as a rescue agent for patients with severe disease who may be experiencing a significant flare or who may be transitioning to another systemic therapy, such as a biologic. Methotrexate is an agent I sometimes use for underinsured individuals. The consideration with methotrexate, though, especially if it's a young person, is thinking about family planning. If they're thinking about becoming pregnant, this is an important consideration with both methotrexate and acitretin. Also, we need to think about their other comorbidities. Do they have a history of liver disease? Do they have metabolic syndrome? Are they more obese? Do they have kidney issues? A lot of patients may not qualify for methotrexate based on comorbidities. Another major consideration is whether they use alcohol on a significant basis.
Feldman: Let me ask you something else about methotrexate. It sounds like we're heavily focused on patients' livers when we're talking about methotrexate because you mentioned their alcohol use. It just made me wonder, is there a role for liver biopsy anymore in those methotrexate-treated patients?
Aldredge: No. That has gone by the wayside. I might send them for a consult for a Fibroscan, which is becoming one of the typical imaging studies we use to assess liver disease. I don't have patients on methotrexate for that long, though. When I've consulted with my liver colleagues, and when a patient's liver functions are okay and they are stable, they don't feel a need to do any further imaging. They haven't done biopsies for years now.
Feldman: Excellent. You mentioned cost. When I really wanted to help somebody in terms of low cost, I would prescribe liquid methotrexate, which was even less expensive than the pills. But I feel as if I haven't done that in so long because the support from companies to get people biologics has been so good. It's sometimes almost easier to get a patient a biologic than it is to make them pay for methotrexate.
Aldredge: And you do have to do liver enzymes. I do a CBC and some baseline testing. Then when a patient first starts therapy, I may bring them back in 6 weeks to recheck their liver and then every 3 months for some time before I feel comfortable that they're stable. Unfortunately, these lab tests cost money, and sometimes patients must pay out of pocket. So, cost is a consideration.
Feldman: Okay. The next drug you mentioned was acitretin.
Aldredge: Yes. Acitretin has been around a long time, but with both methotrexate and acitretin, it takes a long time to see efficacy. If we ramp patients up with it, they can have significant side effects. I have the best luck with acitretin for my palmoplantar psoriasis patients, along with UV-B light therapy. It's not highly efficacious for widespread plaque disease. The side effects I worry about are dry skin and dry eyes — so, tolerability for patients. Again, you have to think about checking triglycerides and lipids, along with liver enzymes. It can be a little bit more cumbersome, but for some patients it's a great option. I've had patients who have been on it for years. It has worked well for them. So, acitretin is still on my menu as I introduce options of oral therapies for patients.
Feldman: Except for women of childbearing potential.
Aldredge: Correct. Along with methotrexate, that is a big concern.
Feldman: Yes. I have trainees who weren't familiar with acitretin, and I can make them real comfortable with it quickly just by telling them that isotretinoin is prescribed to acne patients all the time. The side effect profile is almost identical. The laboratory monitoring is basically the same. If you could do one, you certainly could do the other.
Aldredge: Absolutely.
Feldman: And then we have some newer oral agents.
Aldredge: Yes. The PDE4 inhibitor apremilast has been around for some years now, and it really changed our menu as far as oral therapies. When apremilast was introduced to us, it gave us an option of a very novel mechanism of action and it was incredibly safe. No lab monitoring was required, and it didn't seem to have any pregnancy contraindications for our younger patients. The only issues with apremilast, of course, are the potential side effects of gastrointestinal upset — diarrhea, cramping, nausea, and vomiting. So, when starting this medication, it's necessary to ramp up. It is twice-a-day dosing, which can be cumbersome for some patients, and especially our younger folks living their very busy lives. But it is highly efficacious as far as the oral agents we were using and a great option for patients, especially those with some of the comorbidities I mentioned.
Really, the only other consideration with apremilast is if you have a patient with renal compromise, you may think about going from twice-a-day dosing to once-a-day dosing, but it is otherwise generally well tolerated. For most patients, the gastrointestinal symptoms seem to improve over time, so it could become very well tolerated for some patients. In some individuals it was highly efficacious, with patients reaching clear or near-clear disease. But for the most part, what I continue to see is that it seems to be tolerated for a while, and then patients come to me and say, "Hey, what's new? I feel like I could get a little bit better clearance. I still don't want to be on a biologic, but are there any other new oral therapies?" It also has been a godsend for my patients who may have some other significant comorbidities. They may be going through cancer therapy or surgery. They have a lot of other diseases for which they're taking a lot of medications, and they don't want to be on a biologic. Apremilast is a safe choice that's quite convenient.
Feldman: I get the sense that you hit a home run with oral apremilast maybe one in 10 times. I think most patients have some improvement. I don't think of it as being highly efficacious like some of the biologic options I have. One of the side effects can be weight loss. Most patients, if I tell them, "Unfortunately, one of the side effects is weight loss," they're like, "Oh, that's great. I'd love to lose weight." Have you seen any patients who had excessive weight loss to the point where you considered it an adverse event?
Aldredge: No, I really have not seen that. But I will tell you, for my elderly patients in whom I would worry about more weight loss, it may not be my first option. In my past prescriptions, though, I have never taken a patient off apremilast because of significant weight loss. Have you found that to be the case?
Feldman: Just once. I would have sworn she had cancer from the severity of her weight loss, and then I realized, "Wait a minute, you're on apremilast; let's take you off." And her weight went right back up. We have one even newer agent, deucravacitinib. How are you using it?
Aldredge: When deucravacitinib first came on the scene, we were talking about the concept of a Janus kinase (JAK) inhibitor in the dermatology space, and it was sort of terrifying to everybody, I think. We had learned from our rheumatology colleagues that while this is an efficacious drug in the rheumatology setting, it did come with a baggage of scary side effects. So, when we were thinking about how this is going to work with our more severe psoriasis patients who are more likely to develop some comorbidities, we were worried about giving them a drug that could potentially cause other problems. What we have been pleasantly surprised to see is that the safety profile of this drug is highly efficacious — probably along the lines of tumor necrosis factor–alpha inhibitor biologic therapy — with long-term efficacy but, more importantly, a nice safety profile. Those worrisome side effects we saw with JAK inhibition in our rheumatology patients we are just not seeing in in our dermatology patients.
Mind you, TYK2 is a very specified JAK inhibitor with TYK2 inhibition, which looks very different from the other JAK products we've seen. It has a nice long-term efficacy and a nice safety profile. It seems to be well tolerated by patients. It has once-a-day dosing, which is nice and convenient. However, I think providers are going to have a hard time having the conversation with their patients about the potential side effects if they haven't prescribed it yet. There's no black box warning with this drug. There is recommended lab monitoring that initially should be done, which is also the case with biologics. Deucravacitinib is really a wonderful option as far as a non-PDE4 inhibitor. It's a change from methotrexate and acitretin, with efficacy achieved within a relatively short period of time. And PASI 75 (a 75% or greater reduction in Psoriasis Area and Severity Index scores from baseline) numbers are equivalent to PASI 75 numbers with a biologic.
Feldman: Yes. I think there's a signal for herpes virus infection. Are you getting people up to date on their shingles vaccination before starting this drug?
Aldredge: We recommend that vaccine for all patients. I haven't seen herpes infections and haven't heard about any significant cases of this. But I do think it's important, and I have this conversation with all my patients before starting any systemic therapy, making certain they're up to date on all their immunizations.
Feldman: Let's summarize what we discussed today. Psoriasis management is a team sport, and physician extenders are playing a large and growing role in the management of patients with psoriasis. When we see patients with psoriasis, we could think of it as two diseases — a mild form where patients can get by with just topical therapy, and more extensive or severe involvement where topicals alone are not going to do the trick. While we've had tremendous improvements in psoriasis management with the development of new biologics, we also have new oral agents. So, oral options may be very helpful and especially for patients who are too fearful to consider a biologic therapy. Lakshi, thank you so much for educating our listeners.
Aldredge: Thank you. Dr Feldman, It was a pleasure to speak with you today.
Feldman: Thanks for joining our discussion with our guest, Lakshi Aldridge. There's much more ahead in the coming episodes. In fact, next time, we're going to have Andy Blauvelt discussing biologics vs biosimilars. Be sure to check out the Medscape app and share, save, and subscribe if you enjoyed this episode or look forward to the next one. I'm Dr Steve Feldman for Medscape InDiscussion.
Listen to additional seasons of this podcast.
Resources
Workforce Characteristics of Dermatology Nurse Practitioners
TYK 2 Inhibitors for the Treatment of Dermatologic Conditions: The Evolution of JAK Inhibitors
Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases
Apremilast in Psoriasis and Beyond: Big Hopes on a Small Molecule
Fibroscan (Transient Elastography) for the Measurement of Liver Fibrosis
Deucravacitinib for the Treatment of Psoriatic Disease
Basic Mechanisms of JAK Inhibition
Tumor Necrosis Factor Inhibitors
The Impact of PASI 75 and PASI 90 on Quality of Life in Moderate to Severe Psoriasis Patients
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Cite this: Oral Psoriasis Drugs: What Are NPs Prescribing? - Medscape - Jun 28, 2023.
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