Grace Wright, MD, PhD

In "IL-17 vs IL-23: Head-to-Head Data in Psoriasis and PsA," our experts turn to the trials clinicians actually reach for when choosing a class.

L-17 vs IL-23: Head-to-Head Data in Psoriasis and PsA

Dr. Wright explains that useful comparisons require head-to-head trials in the same patient population. Most head-to-heads in psoriatic disease were done in psoriasis, with adalimumab as a frequent comparator, so many IL-17 and IL-23 agents beat adalimumab on skin. She introduces BE BOLD as a more recent trial pitting an IL-17AF agent against an IL-23 agent on joint-specific measures.

Dr. Wright stresses that comorbidity drives the real-world choice. A patient with psoriatic arthritis plus uveitis or inflammatory bowel disease may not be able to take an IL-17, even if it would serve their skin and joints best. She frames this as thinking across the domains in which psoriatic disease disrupts a patient's life, and welcomes that these agents carry approvals in Crohn's and ulcerative colitis too.

Dr. Han turns to the skin, where nearly every newer medication now sits above adalimumab, though less so on joints. He cautions that nobody runs a trial they expect to lose. He traces the steady rise in mean PASI improvement from about 70% with etanercept, to roughly 75 to 80% with adalimumab and ustekinumab, up to 90 to 95% across the IL-17 and IL-23 classes. He notes that IL-23 versus IL-17 trials often pick secukinumab, the oldest of the newer agents, and choose time points that favor the sponsor, since IL-17s tend to act faster.

Dr. Han argues speed matters to patients even if the difference is measured in weeks, since survey studies show patients value onset. He calls for more special-site comparative trials, citing secukinumab besting ustekinumab on scalp psoriasis as the kind of data clinicians need for scalp, palmoplantar, inverse, and nail disease.

Up next, in "Exploring the IL-17 vs IL-23 Debate in Psoriasis," the panel asks whether the IL-17 versus IL-23 debate is settled, and finds the answer depends heavily on the individual patient.

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This episode, "Targeting the Pathways: TNF, IL-17, and IL-23 in Psoriasis," features the panel unpacking the biology behind today's biologics.

Targeting the Pathways: TNF, IL-17, and IL-23 in Psoriasis

Dr. Wright emphasizes how complex psoriatic disease is, despite looking like just skin and joints. She runs through the targetable pathways: TNF inhibitors, IL-17 inhibitors across the class, whether IL-17A or IL-17AF, and IL-23 inhibitors. She adds agents that work below those pathways, including JAK and TYK2 inhibitors.

Dr. Wright rejects a linear view of the immune response. She describes it as a globe or sphere, where disrupting one node feeds forward and backward through a circuit. Blocking IL-17, for example, can produce feedback that dampens the IL-23 pathway, while TNF-alpha keeps its own distinct receptor and role. Her point is that clinicians must think about the specific molecules and cells in the disease they are treating. She notes that rheumatology once borrowed everything from rheumatoid arthritis, down to its outcome measures, and must now reason from the biology instead.

Dr. Han agrees the discussion was strong but offers a counterpoint for the skin. He argues psoriasis is fortunate to run through a fairly linear central pathway for most patients, flowing through IL-23, TX-17, and IL-17. He acknowledges non-IL-23 sources of IL-17 and other immune circuits exist, but maintains that blocking the central pathway resolves most psoriasis.

Dr. Han frames each successive drug class as more targeted with fewer side effects. He tells patients these therapies are not broadly immunosuppressive, since they narrowly block one overactivated branch while leaving the rest of the immune system intact. That knowledge, he says, puts psoriasis treatment far ahead of where it stood 10 or 20 years ago.

In "IL-17 vs IL-23: Head-to-Head Data in Psoriasis and PsA," Dr. Wright and Dr. Han compare how IL-17 and IL-23 inhibitors perform in the skin and joints, drawing on the head-to-head data that anchors this series.

In "Defining On-Treatment Remission in Psoriasis and PsA," the panel examines whether clear should now mean completely clear.

Defining On-Treatment Remission in Psoriasis and PsA

Dr. Han recounts his work with the National Psoriasis Foundation and its earlier treat-to-target guidelines. Some clinicians resisted them, and he was initially skeptical too. But he came to see the point. With so many effective medicines, the commitment behind systemic treatment is to let patients live a normal life without thinking about psoriasis.

Dr. Han explains the reasoning behind the target. The minimal response worth having on a measure like PASI is around 50%, which is a low bar, and 50% clear is happier but still not where a patient can be. Because current therapies can do far more, he argues clinicians should hold themselves to a higher standard. A cure does not exist yet, so full remission off treatment is not attainable. What is attainable is on-treatment remission: no psoriasis on the body, defined as 0% BSA, PASI 100, or IGA 0.

Dr. Han concedes there is no equivalent on the psoriatic arthritis side, describing patients who bounce between improving joints and flaring skin as therapies get layered on, sometimes back to a TNF. Dr. Wright agrees the field has only nudged from ACR20 to ACR50. She stresses that rheumatology must think across domains, so clear joints with active skin is not remission.

Dr. Wright introduces minimal disease activity, framed as her rule of zeros and ones across enthesitis, dactylitis, and other measures. She notes that MDA requires 5 of 7 criteria, while the stricter VLDA requires all 7. She also flags the harder problem: patients whose joints stay painful despite clear skin, forcing a distinction between residual inflammation and truly treatment-refractory disease.

The next episode in this series, "Targeting the Pathways: TNF, IL-17, and IL-23 in Psoriasis," opens the second section as Dr. Wright walks through the key biologic pathways that drive psoriatic disease.

"Breaking Down Silos: Rheum-Derm Collaboration in Psoriasis Care" takes up the question of how two specialties can stop working in isolation.

Breaking Down Silos: Rheum-Derm Collaboration in Psoriasis Care

Dr. Han describes how lucky he was early in his career to sit next door to rheumatology. He could ask a colleague to look at a patient and talk through medication choices on the spot. When he wanted to start a therapy, he could pick a rheumatologist's brain about preferences and get the patient seen quickly. He took it for granted until he realized how rare that arrangement is. Many clinicians leave residency and find themselves in a silo, which he links directly to burnout.

Dr. Han offers a concrete path forward. A dermatologist can call a local rheumatology office, introduce themselves as trying to establish a referral network, and offer something in return, such as saving a spot or squeezing in an urgent patient. Building that relationship takes a little effort, but most people are receptive, and patients benefit most of all.

Dr. Wright is an enthusiastic proponent of collaborative care. She values that the two specialties see disease differently, with rheumatologists focused on joints and dermatologists on skin, and she appreciates that difference. She believes in using the phone for more than texting. She will call a colleague or send a photo and ask directly whether a patient needs to be seen and how urgently.

Dr. Wright says sharing cases makes her a better rheumatologist at reading skin and makes her dermatology colleagues sharper at spotting joints. Staying in silos forecloses that learning. She recounts intentionally building a community of providers during her years in academia and private practice, so she could always pick up the phone and get a patient in when an emergency arose.

Our next episode, "Defining On-Treatment Remission in Psoriasis and PsA," turns to the concept driving this whole series, with Dr. Han and Dr. Wright defining what remission should mean on the skin and in the joints.

Grace Wright, MD, PhD

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