Dermatologist James Song Talks about Managing Psoriasis with IL-23 Inhibitors | Fall Clinical 2025

The use of interleukin (IL)-23 inhibitors plays an important role in treating patients with psoriasis, as well as in treating other autoimmune diseases. But the use of biologics was complicated by the lack of a definition for failing topical treatments. That is until now.

Last month, the International Psoriasis Council (IPC) published a new article in the Journal of the American Academy of Dermatology to clear up that confusion. E. James Song, M.D., spoke at the 2025 Fall Clinical Dermatology conference in Las Vegas about the new criteria. Song is a dermatologist and co-chief medical officer and director of clinical research at Frontier Dermatology.

IL-23 is a cytokine that plays a crucial role in maintaining and activating Th17 cells, a subset of helper T cells. In autoimmune diseases such as psoriasis, IL-23 becomes overactive and causes Th17 cells to produce excessive amounts of inflammatory substances.

IL-23 inhibitors are a class of biologic medications; they attach to IL-23 and prevent it from activating Th17 cells. This reduces inflammation and can be used with less frequent dosing than biologics that target IL-17. Several IL-23 biologics are on the market to treat psoriasis, including Skyrizi (risankizumab), Tremfya (guselkumab) and Ilumya (tildrakizumab).

In an interview with Dermatology Times, a sister publication of Managed Healthcare Executive, Song provided an overview of managing patients with psoriasis with IL-23 inhibitors, as well as a brief look at the psoriasis pipeline.

Q: What are the criteria for treating patients with psoriasis with systemic therapies?

A: To get around some of the limitations with using body surface area as the only measure of disease severity, the IPC, under the guidance of Dr. Bruce Strober, recommended that we recategorize disease severity and move away from mild, moderate and severe based on body surface area alone. The recommendation was to simply put patients into two different buckets: a topical patient or a systemic patient.

To qualify for systemic treatment, patients need to meet just one of three criteria. You have greater than 10% body surface area, or you have a high-impact area that’s affected, like the scalp or genital skin, for example, or you fail a topical therapy. But it’s the third criterion that wasn’t as well defined because topical failure can mean a lot of different things. Is it because you didn’t get better? Is it because you don’t like the vehicle? Is it because you just had a hard time being compliant?

The IPC recently published its definition of a topical treatment failure. According to these guidelines, if you’ve tried two consecutive four-week courses of a topical therapy, and you fail to get to a body surface area of 1% or less, or a PGA [physician global assessment] of clear or almost clear, then you should be deemed a topical failure. We also give special considerations for patients who may rate their disease as being more moderate or severe, even if a clinician calls it mild, or patients who might have a high symptom burden, or patients who are having to overly rely on potent or ultra-potent topical cortical steroids.

Q: Is there any new data on IL-23 inhibitors?

A: We presented new data on using IL-23 inhibitors like risankizumab and guselkumab in patients who have high-impact areas that are involved but have relatively low body surface area [measurement]. What we saw consistently with both medications is that we’re getting very high levels of clearance across these different high-impact areas, which should give you confidence in using these therapies in patients who might have a low body surface area involved but still have some of these high-impact areas affected.

Q: What did you see in terms of drug persistence with IL-23 inhibitors?

A: Drug persistence, or what we call drug survivability, is a great surrogate for how well a drug works, how well it’s tolerated, and the safety, but also for the insurance coverage and compliance piece. It’s a good measure of all of these things combined in one, and we have various different ways that we can do real-world drug persistence studies, whether that's coming from historical or claims data.

We reviewed several of the larger studies that have been done in the space. What we have seen very consistently is that patients discontinue their first biologic for all sorts of different reasons, and that number could be fairly high; anywhere from 20% to 40% of patients will stop because of inadequate efficacy, safety, tolerability, or sometimes because of insurance reasons.

What all these data sets have shown is that the IL-23 class, whether it's risankizumab or guselkumab, has the highest levels of drug persistence over the course of three years. If you start one of these two medications, you are far more likely to stay on those two medications than any other medication that we have for psoriasis. And that’s important, because when we think about disease remission, not only do we want to get patients to completely clear, but we want to maintain clear for as long as we can. The durability piece is going to be very, very important. We see that the IL-23 class is very good in this area.

Q: Is there anything in the psoriasis pipeline that you are looking forward to?

A: 2026 is going to really be an exciting year for us, one that really marks the era of oral therapies and psoriasis. Despite having several oral therapies for psoriasis, none have matched the efficacy and the safety of some of our newer biologics.

That might change in 2026 because we now have three novel oral therapies. One is an oral peptide that blocks the IL-23 receptor, and the other two are second-generation TYK2 inhibitors that bind to that allosteric domain with much higher potency and much higher affinity. We’ve seen this translate potentially to not just better levels of efficacy but also a rapid onset, as well as a very good safety profile. We are positioned in 2026 to now give our patients the flexibility of a pill or a shot.