The Latest on Systemic Agents for Psoriasis: A Q&A With Jashin J. Wu, MD, FAAD

The pharmacologic pipeline continues to produce strong options for systemic treatment of psoriasis. Practical Dermatology® spoke with Editorial Board member Jashin J. Wu, MD, FAAD, Founder and CEO of the Dermatology Research and Education Foundation, to discuss the latest treatment considerations with these agents.

What have been the most important recent developments in the treatment of psoriasis?

Dr. Jashin Wu: The Cochrane Database of Systemic Reviews analyzed a number of systemic agents for treating psoriasis, and they ranked the most effective: infliximab, bimekizumab, ixekizumab, and risankizumab.¹ My two favorites are risankizumab and bimekizumab; in my opinion, they are the most effective agents, period. Bimekizumab is the most effective. Risankizumab offers an advantage based on its dosage—every 12 weeks, for maintenance, compared with every 4 to 8 weeks for bimekizumab, depending on the dosing regimen you choose (for patients weighing ≥ 120 kg, you can consider a dose of 320 mg every 4 weeks after Week 16). Bimekizumab is not yet approved by the US Food and Drug Administration (FDA) for psoriatic arthritis, though I expect it to be soon. Those are clearly the best two agents for psoriasis systemically. 

Is there anything in the pipeline that you’re excited about?

Dr. Wu: There are some oral agents that are blocking interleukin-17 and interleukin-23. Obviously, we have biologics that target those cytokines, but it is worth looking at these agents in an oral fashion. Janssen has an interleukin-23 inhibitor that is an oral agent. They presented the phase 2 data at the World Congress of Dermatology in Singapore last year. It was very impressive, so it is now in phase 3. I am guessing it may be the most effective oral agent once it is approved. Takeda has a tyrosine kinase 2 inhibitor that is similar to deucravacitinib; they presented phase 2b data at the American Academy of Dermatology (AAD) Annual Meeting in March 2023, and it looked impressive, so that is also in phase 3 studies. 

How does the understanding of genetics and immunology impact the ability to treat psoriasis? 

Dr. Wu: It is important, and there is still more to learn. We know which genes cause psoriasis, but there is no way to actually block those genes from expressing psoriasis yet. That is probably years away. However, some personalized medicine advances have emerged in the last few years. Mindera offers a swab that basically determines which class of biologic for psoriasis may be the most effective for that particular patient. It will say, for example: The positive predictive value for interleukin-23 inhibitors for this patient is 95%, for TNF inhibitors it is 50%, and for the interleukin-17 blockers it is 80%. You would then recommend the interleukin-23 blockers. 

Do you recommend any combination therapies with systemic agents?

Dr. Wu: Currently, for severe psoriasis, a monotherapy is typically all that is needed. However, that may not be enough for all patients. If a patient has some minor breakthroughs, I recommend non-steroidal cream, such as roflumilast or tapinarof. For scalp psoriasis, you can certainly recommend roflumilast foam. For a more severe case, you may want to change the monotherapy biologic or just add something like methotrexate or apremilast. 

How important is patient awareness of the fact that there are so many strong biologic options?

Dr. Wu: It is definitely important. When I started my residency, we just had etanercept, infliximab, and adalimumab. Patients may have become frustrated with those limited options and given up. Years later, they may not be aware of all these newer, amazing agents that can help them a lot. However, that is probably less common now, especially with so much direct-to-consumer advertising. Most patients have seen and heard commercials for these psoriasis agents, so there is probably more awareness now than ever before, but some patients still probably are not on what they should be on. In some cases, perhaps the patient is aware of the options, but the dermatologist is hesitant about prescribing biologics and recommends creams instead. That is a major disservice to patients. The dermatologist’s awareness of the safety of these agents might be the most important key now. 

Are there any particular misconceptions about safety issues that you would want to dispel? 

Dr. Wu: Many people think systemic agents are dangerous. The data show, especially for the new agents, that they are not. If anything, there may be more danger in not using them. Studies conducted by myself and others have indicated that treating psoriasis may actually improve comorbidities of psoriasis, such as cardiovascular disease.

What are some other important comorbidities to be particularly aware of? 

Dr. Wu: Psoriatic arthritis is the most common one and probably the most important one because about one-third of psoriasis patients will have psoriatic arthritis. Cardiovascular disease is certainly up there as well—there is a risk of hypertension, dyslipidemia, and diabetes, and then the risks of heart attack, stroke, and cardiovascular death are increased. Of course, psychiatric comorbidities are important as well. These patients definitely have a higher risk of depression, anxiety, and suicidal ideation. 

What do you recommend for patients with more mild psoriasis?

Dr. Wu: With the availability of roflumilast and tapinarof, both of which are non-steroidal agents, I propose that they should be used as the first line for mild psoriasis. They are almost as effective as class I steroids, and they are significantly safer and simpler. You do not need to tell the patient to use a steroid twice a day for two weeks, something else for two weeks, and then go back to the steroid. You do not need to give them a foam for the scalp, a cream for the body, and a lotion for the groin area. That is too much, and patients get confused. They may use the same steroid everywhere, which can be harmful. With roflumilast and tapinarof, however, we can just give them one agent and tell them to use it once a day. It is so simple and easy. 

1. Sbidian E, Chaimani A, Garcia-Doval I, Doney L, Dressler C, Hua C, Hughes C, Naldi L, Afach S, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2022 May 23;5(5):CD011535. doi: 10.1002/14651858.CD011535.pub5.

Reference

Engel PV, Smith B, Javadi SS, Wu JJ. It is time to consider a new topical algorithm for psoriasis. J Am Acad Dermatol. 2024 Feb;90(2):e84-e85. doi: 10.1016/j.jaad.2023.07.1048.