IL-23 or IL-17 for Preventing Psoriasis Progression into PsA, With Andrew Blauvelt, MD, MBA

The longstanding debate over IL-23 versus IL-17 inhibitors in moderate to severe plaque psoriasis has largely been framed around skin clearance — a competition that most experts characterize as effectively too close to call. At the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, Colorado, that debate extended to a more clinically consequential and mechanistically charged question: whether biologic class selection in psoriasis patients without current joint involvement might determine who goes on to develop psoriatic arthritis.

Andrew Blauvelt, MD, MBA, owner of Blauvelt Consulting, in Annapolis, Maryland, and a principal investigator on the ONWARD program, argued the affirmative in a formal debate at the meeting, with Richard Langley, MD, professor of dermatology at Dalhousie University in Halifax, Nova Scotia, taking the opposing view. The debate drew on an emerging body of observational evidence suggesting that treatment with IL-23 pathway inhibitors — agents targeting the IL-23p19 subunit such as guselkumab, risankizumab, and iltaekizumab — may reduce the rate of PsA development in patients with psoriasis who do not yet have joint disease.

The clinical context for the debate is well established. Up to 30% of patients with psoriasis develop PsA over their disease course, with a lag of 5 to 7 years on average between skin and joint onset — a window that, in principle, creates an opportunity for preventive intervention. IL-17 inhibitors are currently regarded by most experts as the preferred biologic for patients who already have established PsA, given their more robust joint outcome data from controlled trials. The more provocative and contested question is whether IL-23 inhibitors might have a distinct preventive role upstream of PsA onset — a hypothesis Blauvelt characterized as biologically coherent in a conversation with HCPLive.

IL-23 is an orchestrator cytokine sitting proximal to multiple downstream inflammatory cascades, including the IL-17 axis; inhibiting it theoretically disrupts the upstream regulatory signal before it can drive synovio-entheseal inflammation, rather than blocking the downstream effector cytokine once the inflammatory cascade is already established.

Several observational analyses have provided preliminary support for this hypothesis. Real-world studies of patients with psoriasis and early musculoskeletal symptoms treated with IL-23 inhibitors have reported lower rates of PsA progression compared with historical rates and with patients on other biologic classes. The ongoing PAMPA (Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort) trial, a randomized, double-blind, placebo-controlled phase 4 study, is directly testing this hypothesis prospectively, with guselkumab versus placebo in psoriasis patients at elevated PsA risk; co-primary endpoints include a power Doppler ultrasound musculoskeletal score at week 24 and the proportion of patients with new PsA at week 96. PAMPA data are not yet mature.

The central methodological objection to the existing observational evidence — and the core of Langley's opposing argument — is selection bias. In routine practice, patients with any musculoskeletal symptoms are more likely to be placed on IL-17 inhibitors, which have established joint efficacy, while patients without joint involvement are more likely to receive IL-23 inhibitors. If this prescribing pattern holds across the observational datasets, then the apparently lower PsA incidence in IL-23-treated cohorts may simply reflect the fact that those patients were less predisposed to joint disease at baseline — not that the drug prevented it. Conversely, IL-17-treated cohorts may appear to have higher PsA rates because they were enriched for patients already on a joint disease trajectory. Blauvelt acknowledged this confounding risk directly, framing it as the critical limitation of the current literature and the reason prospective randomized data from PAMPA and similar trials are needed to settle the question.

The debate did not yield a consensus — nor was it designed to — but it distilled the clinical decision point that will face dermatologists as the evidence base matures: whether, for a psoriasis patient without current joint symptoms but with risk factors for PsA progression such as nail disease, scalp involvement, high body mass index, or a family history of PsA, IL-23 inhibition should be considered not only for skin control but as a strategy to delay or prevent joint disease onset. Blauvelt's position is that the mechanistic rationale is compelling and the emerging observational data are hypothesis-generating enough to take seriously, even before prospective confirmation. Langley's counterpoint is that prescribing decisions of this magnitude require randomized evidence that does not yet exist, and that acting on biologically plausible but methodologically compromised data risks systematically misallocating treatment in a disease where IL-17 inhibitors offer established and proven joint protection.

“Anybody with any kind of musculoskeletal disease may have preferentially been put on 17 blocker, and then they may be more predisposed to develop PsA. So that's the controversy. I'm taking the stance that 23 blockers do indeed have the potential to block PsA,” Blauvelt said.

Reference

Langley RG, Blauvelt A. Debate: IL-23 versus IL-17 inhibitors — does biologic class prevent psoriatic arthritis development? Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.