Andrew Blauvelt, MD 

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 

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.

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.

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Are IL-23 inhibitors, rather than IL-17 inhibitors, the preferred biologic for psoriasis patients at risk of developing psoriatic arthritis?

Understanding Patient Preferences in Psoriasis, With Andrew Blauvelt, MD, MBA

As a wave of new oral therapies approaches regulatory review for moderate-to-severe plaque 

 (PsO), a better understanding is needed of what factors may affect patient preference toward different modalities of treatment.

caught up with Andrew Blauvelt, MD, MBA, dermatologist, Blauvelt Consulting, at the 

2026 American Academy of Dermatology (AAD) Annual Meeting

 held in Denver, Colorado, from March 27-31, to learn more about how the field is coming to better understand and support patient preferences.

In this conversation, Blauvelt pushed back on what he described as a reflexive tendency to assume that the availability of once-daily oral options will automatically translate into patient demand. The reality, he noted, is considerably more nuanced. Across several published preference studies he reviewed, the direction of patient preference varied substantially depending on disease, severity, injection characteristics, and country of origin.

In 1 study comparing patients with atopic dermatitis and psoriasis on the question of route-of-administration preference, the 2 groups diverged: atopic dermatitis patients favored oral therapy, while psoriasis patients expressed a preference for injectable treatment.

 A second psoriasis-specific study found that disease severity modulated preference within the same patient population — those with more moderate disease leaned toward pills, while patients with more severe disease preferred injections.

The implication, Blauvelt noted, is that 2 studies conducted in the same disease reached different directional conclusions depending on how the question was asked and which patients were enrolled.

Geographic context introduced additional variation. A study conducted in Japan found a clear preference for oral therapy, while a comparable study conducted in Germany yielded the opposite result, with German patients favoring injections.

 And a further study found that what mattered most was not simply whether a treatment was injectable, but what kind of injection it was: patients preferred shots when they were infrequent — monthly or less — and not painful, but shifted toward pills when injections were more frequent or associated with discomfort.

Blauvelt framed these findings as relevant context for interpreting the clinical landscape now emerging around envudeucitinib, zasocitinib, and icotrokinra, each of which offers once-daily or twice-daily oral dosing and carries efficacy data approaching or overlapping with injectable biologics in some measures. The case for oral therapy is real, he argued, but it is not universal — and the patients most likely to benefit from the shift to pills may be those with moderate disease, those averse to injections for logistical or geographic reasons, and those in clinical settings where biologic prescribing remains limited. For patients with more severe disease who are already on well-tolerated, infrequent injectable biologics, the calculus may be less straightforward than the narrative around the oral pipeline sometimes suggests.

Blauvelt’s disclosures include Abbvie, Almirall, Alumis, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis Biotherapeutics, Eli Lilly, Incyte, Janssen, LEO Pharma, Lipidio Pharma, Novartis, Oruka Therapeutics, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharma, Takeda, and UCB.

Royeck S, et al. Treatment preferences among systemic therapy-naïve patients with atopic dermatitis or psoriasis in Germany: a multicentre study. 

Komine M, et al. A discrete choice experiment on oral and injection treatment preferences among moderate-to-severe psoriasis patients in Japan. 

. 2023;50:766-777. doi:10.1111/1346-8138.16746

Bolt T, Kobayashi H, Mahlich J. Patient and physician preferences for therapy characteristics for psoriasis: a discrete choice experiment in Japan. 

. 2019;3(2):255-264. doi:10.1007/s41669-018-0104-1

Blauvelt discusses studies revealing that disease severity, injection frequency, pain, and geography all shape treatment preferences.



How Envudeucitinib May Fit Into the Evolving Oral Psoriasis Landscape, With Andrew Blauvelt, MD, MBA

 held in Denver, Colorado, from March 27-31, marked a watershed moment for the oral psoriasis treatment landscape, with late-breaking phase 3 data presented for 2 next-generation TYK2 inhibitors — envudeucitinib and zasocitinib — arriving just weeks after the FDA approval of icotrokinra (Icotyde), the first oral IL-23 receptor antagonist approved for moderate to severe plaque psoriasis. Andrew Blauvelt, MD, MBA, owner of Blauvelt Consulting, in Annapolis, Maryland, and a principal investigator on the ONWARD program, spoke about where envudeucitinib fits in the context of this rapidly expanding field. 

Blauvelt characterized envudeucitinib as a second-generation TYK2 inhibitor specifically engineered for complete 24-hour target coverage — distinct from the first approved agent in the class, deucravacitinib — and the only TYK2 inhibitor to date shown to achieve maximal inhibition over a full dosing interval in humans. The ONWARD1 and ONWARD2 trials together enrolled more than 1,700 adults with moderate to severe plaque psoriasis, randomized 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or the active comparator apremilast, with co-primary endpoints of PASI 75 and static Physician's Global Assessment (sPGA) 0/1 at week 16. Both studies met all primary and secondary endpoints with high statistical significance versus placebo (

 <.0001). At week 16, approximately 74% to 75% of envudeucitinib-treated patients achieved PASI 75 and 59% achieved sPGA 0/1. Response continued to deepen through week 24, at which point approximately 80% achieved PASI 75, approximately 65% achieved PASI 90, and more than 40% achieved PASI 100 — complete skin clearance. Envudeucitinib outperformed apremilast on all PASI endpoints at week 24 (

 <.0001), with separation from placebo on PASI 90 observed as early as week 4. The safety profile was favorable and consistent with phase 2 findings, with nasopharyngitis and upper respiratory tract infection the most common adverse events and notably no lipid signal of the type observed in earlier deucravacitinib studies.

Zasocitinib, Takeda's once-daily investigational TYK2 inhibitor, presented concurrent phase 3 data from the LATITUDE PsO 3001 and 3002 trials at the same meeting. In those studies, 71.4% and 69.2% of zasocitinib-treated patients achieved sPGA 0/1 at week 16 versus 10.7% and 12.6% with placebo (

 <.001), with PASI 75 responses observed as early as week 4 and more than 90% of week 40 responders maintaining response through week 60. Also arriving just before AAD, icotrokinra received FDA approval on March 18, 2026 as the first targeted oral peptide to precisely block the IL-23 receptor, with approval based on the phase 3 ICONIC program in approximately 2,500 patients. In the ICONIC-ADVANCE head-to-head studies, approximately 70% of patients achieved IGA 0/1 and 55% achieved PASI 90 at week 16, with icotrokinra demonstrating superiority over deucravacitinib at weeks 16 and 24.

Blauvelt placed these 3 agents in direct relation to one another, noting that the best IL-23 and IL-17 biologics likely still represent the ceiling for skin clearance. For patients prioritizing maximum efficacy, he would continue to favor those agents; however, for the many patients who prefer oral therapy and the many clinicians who remain reluctant to prescribe biologics, he characterized icotrokinra, envudeucitinib, and zasocitinib as agents that will move immediately to the top of the oral treatment hierarchy. He noted that dosing may be an early point of practical differentiation — zasocitinib and icotrokinra are once daily, while envudeucitinib is currently dosed twice daily, though Alumis has indicated plans to develop an extended-release once-daily formulation. He also raised the possibility that performance in psoriatic arthritis could ultimately drive prescribing choices among these agents if data reveal meaningful differences in joint outcomes. An NDA submission for envudeucitinib is planned for the second half of 2026.

Blauvelt A, Sofen H, Armstrong A, et al. Envudeucitinib (ESK-001) in moderate-to-severe plaque psoriasis: 24-week results from the randomized, double-blind, active comparator- and placebo-controlled, phase 3 ONWARD1 and 2 studies. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

Alumis Inc. Alumis' envudeucitinib delivers early and robust improvements in skin clearance, quality of life and psoriasis symptoms in two phase 3 trials, underscoring its potential as a leading oral therapy for plaque psoriasis. Press release. March 28, 2026. Accessed March 28, 2026. 

https://investors.alumis.com/news-releases/news-release-details/alumis-envudeucitinib-delivers-early-and-robust-improvements

Gooderham M, et al. Once-daily oral zasocitinib demonstrates rapid and reproducible skin clearance with a consistent safety profile in moderate-to-severe plaque psoriasis: results from two randomized phase 3 trials (LATITUDE-PsO-3001 and 3002). Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

Johnson & Johnson. FDA approval of ICOTYDE™ (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. Press release. March 18, 2026. Accessed March 28, 2026. 

https://www.investor.jnj.com/investor-news/news-details/2026/FDA-approval-of-ICOTYDE-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide/default.aspx

Phase 3 ONWARD data for the investigational TYK2 inhibitor envudeucitinib join a rapidly crowding oral psoriasis space.


ONWARD: Oral Envudeucitinib Demonstrates High PASI Responses in Phase 3, With Andrew Blauvelt, MD

Phase 3 data for envudeucitinib — a next-generation, highly selective oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition — have demonstrated robust skin clearance in moderate-to-severe plaque psoriasis (PsO), in new data presented at the 

 held in Denver, Colorado, from March 27-31.

To discuss the findings, we spoke with Andrew Blauvelt, MD, MBA, Owner of Blauvelt Consulting, LLC, in Annapolis, Maryland, and a principal investigator on the ONWARD program, following his late-breaking oral presentation at the meeting. The ONWARD1 and ONWARD2 trials together enrolled more than 1,700 adults with moderate-to-severe plaque psoriasis, randomized 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or the active comparator apremilast, with co-primary endpoints of PASI 75 and static Physician's Global Assessment (sPGA) 0/1 at week 16. Both studies met all primary and secondary endpoints with high statistical significance versus placebo (

At week 16, approximately 74–75% of envudeucitinib-treated patients achieved PASI 75 and 59% achieved sPGA 0/1 — substantially higher than both placebo and apremilast. Blauvelt highlighted the week 24 data as particularly noteworthy: consistent with the class behavior of TYK2 inhibitors, response deepened over time, with approximately 80% achieving PASI 75, approximately 65% achieving PASI 90, and more than 40% achieving PASI 100 — complete clearance — by week 24. Envudeucitinib outperformed apremilast on all PASI endpoints at week 24 (

 <.0001), and separation from placebo on PASI 90 was observed as early as week 4. Patient-reported quality-of-life and itch measures were consistent and clinically meaningful throughout. 

On safety, the profile was favorable and consistent with phase 2 findings — the most common adverse events were nasopharyngitis and upper respiratory tract infection, with no major cardiovascular events, no tuberculosis reactivation, no clinically relevant hematologic or metabolic laboratory abnormalities, and notably no lipid signal of the kind observed in earlier deucravacitinib studies. 

Blauvelt distinguished envudeucitinib from deucravacitinib as a second-generation TYK2 inhibitor specifically engineered for complete 24-hour target coverage — the only TYK2 inhibitor shown to achieve maximal inhibition over a full dosing interval in humans. An NDA submission is planned for the second half of 2026, with a once-daily extended-release formulation and a pediatric program both in development.

“[This was] a major reveal… phase 3 results for a new oral drug for psoriasis called envudeucitinib, next gen TYK2 inhibitor. If all goes well, if the FDA likes it… usually when phase 3 results are presented at AAD, oftentimes, we will see approval of the drug in the coming year,” Blauvelt said.

Blauvelt A, Sofen H, Armstrong A, et al. Envudeucitinib (ESK-001) in Moderate-to-Severe Plaque Psoriasis: 24-Week Results From the Randomized, Double-Blind, Active Comparator- and PlaceboControlled, Phase 3 ONWARD1 and 2 Studies. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31. 

Alumis Inc. Alumis' envudeucitinib delivers early and robust improvements in skin clearance, quality of life and psoriasis symptoms in two phase 3 trials, underscoring its potential as a leading oral therapy for plaque psoriasis. Press release. March 28, 2026. 

Blauvelt discussed highlights from the phase 3 ONWARD1 and ONWARD2 clinical trials presented at AAD 2026.

Andrew Blauvelt, MD

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