<p>Plaque psoriasis therapeutics have expanded from primarily topical agents to a rich mix of biologics and oral therapies. This article offers a physician assistant’s perspective on navigating today’s treatments for moderate to severe plaque psoriasis, emphasizing clear screening, patient-fit dosing, and an awareness of emerging treatment strategies.</p> <p><br></p> <p><em>Following the 6th Annual Elevate-Derm Fall Conference, featured expert Douglas DiRuggiero, DMSc, MHS, PA-C, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Mr DiRuggiero are presented here</em><em>.</em></p>

It is an exciting time in the therapeutic world of plaque psoriasis. When I started my dermatology career in 2000, we were using topical steroids, coal tar, anthralin, phototherapy, methotrexate, and cyclosporine. The first biologic for moderate to severe plaque psoriasis became available in 2004, and that launched a treatment renaissance that continues today. In fact, every year from 2013 to 2020, we had a new systemic therapy approved by the US Food and Drug Administration (FDA) for plaque psoriasis. It can be daunting to be a new clinician entering the psoriasis world, as there are a lot of pharmaceuticals out there now.

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We currently have 12 biologics that are FDA approved for moderate to severe plaque psoriasis. Four are TNF inhibitors; 3 can be self-administered and 1 (infliximab) is an intravenous medication that requires an infusion center for administration. TNF inhibitors do carry boxed warnings regarding risks of infections and malignancy. They also have some strong warnings and precautions to consider. I have not actually prescribed a TNF inhibitor for plaque psoriasis in several years because, once IL-17 and IL-23 inhibitors became available, we had biologic options that were cleaner, had more convenient dosing schedules, and had the same efficacy as TNF inhibitors or higher.

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We now have 4 IL-17 inhibitors that are approved by the FDA for moderate to severe plaque psoriasis. The first to be approved was secukinumab in 2015, followed by ixekizumab and then brodalumab. The newest IL-17 inhibitor is bimekizumab. These medications are phenomenally good at getting patients’ plaque psoriasis clear and keeping them clear for long periods.

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We also have 3 IL-23 inhibitors and 1 IL-12/23 inhibitor (ustekinumab). The first IL-23 inhibitor to come to market for plaque psoriasis was guselkumab, followed by tildrakizumab and then risankizumab. IL-23 inhibitors introduce a more convenient dosing schedule; for example, guselkumab is dosed every 8 weeks, and risankizumab and tildrakizumab are dosed every 12 weeks. Guselkumab and risankizumab are also indicated for the treatment of psoriatic arthritis. If I have a really strong joint concern with a patient, guselkumab may be my first choice, as the recent APEX study data that came out last summer showed that guselkumab inhibits radiographic structural damage progression.

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So, when you sit down with a patient who has plaque psoriasis and is interested in biologic therapy, you must ask several questions to find the best therapy for them. For example, do you have a history of infections? Do you have a history of malignancy? Have you ever been told that you have optic neuritis, Guillain-Barré syndrome, or any other type of demyelinating disease? Have you ever been told that you have congestive heart failure? If the answer to any of these questions is yes, you are not heading toward using a TNF inhibitor. If the patient has a history of inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis, then we tend to avoid IL-17 inhibitors. For patients with a history of IBD, you may consider an IL-23 inhibitor; some drugs in this class have FDA approval for both psoriatic disease and IBD.

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Finally, we also have 2 nonbiologic oral medications for moderate to severe plaque psoriasis. One is the PDE4 inhibitor apremilast, which was approved by the FDA in 2014. The efficacy of apremilast is less than that of biologic therapy, but it is the only oral pill that I can initiate in the office with no laboratory monitoring requirements. Also, apremilast is the only systemic therapy indicated for mild, moderate, and severe disease, as well as the only plaque psoriasis medication that is indicated in patients down to age 6, for both psoriatic arthritis and plaque psoriasis. It is important to ask and warn patients about depression with apremilast because precautions are in the label.

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The second oral medication for plaque psoriasis is deucravacitinib, which is a TYK2 inhibitor that is indicated for moderate to severe disease in adults. Head-to-head efficacy data against apremilast showed that deucravacitinib is superior to apremilast but not as strong as the biologics. Deucravacitinib is only dosed once daily, whereas apremilast is dosed twice daily. While it does require some laboratory monitoring, deucravacitinib does not have boxed warnings like the other recently FDA-approved JAK inhibitors.

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There are ongoing trials that are evaluating combining some of the already-approved biologics. Trials that are combining medications that work outside of the cell (eg, IL-17 and IL-23 inhibitors) with medications that work inside of the cell (eg, JAK and TYK2 inhibitors) are certainly exciting to anticipate. Immediate excitement surrounds a new oral peptide tablet, icotrokinra, which is an IL-23 receptor blocker. The data for this “non-JAK, nonbiologic” oral therapy are interesting because we are seeing Psoriasis Area and Severity Index (PASI) 90 scores that are close to some of the biologics. Icotrokinra has not been FDA approved, but it is coming very soon, and this agent will be a good oral option for our patients with psoriasis.