Grace Wright, MD, PhD

In "BE BOLD Head-to-Head: IL-17 vs IL-23 for Psoriasis and PsA," the panel digs into the trial that broke the usual non-inferiority pattern.

BE BOLD Head-to-Head: IL-17 vs IL-23 for Psoriasis and PsA

Dr. Wright describes BE BOLD as a phase 3b head-to-head comparing bimekizumab, an IL-17A/F inhibitor, against risankizumab, an IL-23 inhibitor, in psoriatic arthritis. Skin burden was low, with baseline PASI around 3 rather than above 10, which changes how that measure performs. At week 16, roughly four months, bimekizumab reached ACR50 more often, 49% versus 38%, an 11-point split maintained through week 24.

Dr. Wright argues an 11% difference is meaningful, matching the ranges that separate drugs and ACR thresholds. On the stricter ACR50-plus-clear-skin endpoint, bimekizumab led numerically, 33.5% versus 24.4%, though not to statistical significance. Safety was comparable except for the candida infections expected with IL-17, which she frames as manageable and non-systemic. She calls it a win to finally differentiate pathways as better rather than merely non-inferior, in the same modern patient population rather than across separate trials.

Dr. Han says the design deliberately aimed for superiority, and existing skin data already show bimekizumab hitting the highest PASI 100 rates at earlier time points. He calls it the most well-rounded agent for patients bouncing between skin and joints, and credits the trial for going after risankizumab, a popular high-market-share drug, rather than a weaker comparator.

Dr. Han then discusses a 2026 retrospective analysis of a claims database suggesting IL-23s carried the lowest risk of developing psoriatic arthritis. He urges caution given methodological limits, such as billing artifacts, and the journal it landed in. He notes clinicians can reasonably start with the most effective option for both domains or defer it and switch later. He closes on candidiasis, noting most patients do not get recurrent episodes, and advises making decisions based on science rather than fear.

Our next episode, "IL-17 Inhibitor Safety in Psoriasis: Candidiasis, IBD, and Mental Health," turns to the safety profile of IL-17 inhibitors in depth, from candidiasis to inflammatory bowel disease and mental health.

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"Exploring the IL-17 vs IL-23 Debate in Psoriasis " takes up a deliberately provocative question from the moderator.

Exploring the IL-17 vs IL-23 Debate in Psoriasis

Dr. Wright says the answer is complicated. For axial psoriatic arthritis she reaches for an IL-17, a TNF, or a JAK, because the supporting data are stronger there. Peripheral, hands-and-feet disease is less complicated to treat. She insists on paying attention to the axial skeleton and distinguishing degenerative from inflammatory disease, since the nuances differ.

Dr. Wright returns to a measurement problem. Against adalimumab the joints have consistently been non-inferior rather than clearly better. She explains that ACR50 means at least 50% improvement, so a patient could be at 65% or 69% and still be counted the same. That wide span makes nuanced differences between drugs hard to detect.

Dr. Han describes a strong preference for IL-23s in many dermatology offices. Clinicians appreciate their simplicity when there are no comorbidities like inflammatory bowel disease to weigh, their less frequent dosing, and newer oral IL-23 peptides that need no lab monitoring or TB screening. He addresses claims that IL-23s are more durable or better for heavier patients with a grain of salt, noting every biologic loses efficacy at the highest weight ranges.

Dr. Han cautions against holding beliefs too strongly against newer data. He recounts a surprising finding that an IL-23 inhibitor failed in phase 2 trials for axial disease, which was counterintuitive given the shared cytokines. He contrasts that with guselkumab's modestly positive axial signal on patient-reported outcomes. His closing point is that clinicians are lucky to have strong options across the board and can now tailor first-line choices to what matters most to each patient, from onset speed to joint involvement.

The next episode in this series, "BE BOLD Head-to-Head: IL-17 vs IL-23 for Psoriasis and PsA," features Dr. Wright walking through the BE BOLD head-to-head trial in detail and what its results mean.

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.

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.

Grace Wright, MD, PhD

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