Philip J. Mease, MD

Validating Deucravacitinib’s Anticipated Expansion to Psoriatic Arthritis, with Philip Mease, MD

The psoriatic arthritis (PsA) field is looking forward to the potential addition of a new mechanism of action to the treatment landscape – deucravacitinib, an oral, selective TYK2 inhibitor already approved for people with psoriasis.

Based off of positive data from the phase 3 POETYK PsA-1 trial, the latest findings from which were presented at the

 European Alliance of Associations for Rheumatology (EULAR) Congress

 in June in Barcelona, Spain, Bristol Myers Squibb submitted and the FDA accepted the supplemental New Drug Application (sNDA) for the PsA indication with a Prescription Drug User Fee Act (PDUFA) goal date of March 6, 2026.

As presented at EULAR, POETYK PsA-1 met its primary endpoint of achieving ACR20 response at week 16 compared to placebo (54.2% vs 34.1%; 

<.0001) in adults with active PsA who were not previously treated with a biologic disease-modifying anti-rheumatic drug (bDMARD).The trial also met key secondary end points including Psoriasis Area and Severity Index (PASI) 75 response (51.9% vs 7.1%; 

 <.0001), Health Assessment Questionnaire-Disability Index (HAQ-DI) score (-.39 vs -.22; 

 <.0001), 36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) score (6.06 vs 3.71; 

 <.0001) and Minimal Disease Activity (MDA) response (19.0% vs 10.2%; 

 spoke with study investigator Philip Mease, MD, director of rheumatology research at Providence Swedish Medical Center and clinical professor at the University of Washington School of Medicine, Seattle, to learn more about how the new data add to the field’s knowledge of deucravacitinib’s safety and efficacy for people with PsA and the potential the therapy may have in improving disease outcomes.

“It appears to have a more pristine safety profile, even [more so] than some of the JAK1 or JAK3 inhibitors. I think that patients will appreciate having a safe drug that can be used, especially early on, in PsA,” Mease said.

Relevant disclosures include AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Genentech, Janssen, Novartis, Pfizer Inc, Sun and UCB.

Kunzmann K. FDA Approves Deucravacitinib for Adults with Plaque Psoriasis. HCPLive. September 12, 2022. 

https://www.hcplive.com/view/fda-approves-deucravacitinib-adults-plaque-psoriasis

Bristol Myers Squibb’s Supplemental New Drug Application (sNDA) for Sotyktu (deucravacitinib) for the Treatment of Adults with Active Psoriatic Arthritis Accepted for Review Across Four Regions Globally. News release. Bristol Myers Squibb. July 21, 2025. 

https://news.bms.com/news/details/2025/Bristol-Myers-Squibbs-Supplemental-New-Drug-Application-sNDA-for-Sotyktu-deucravacitinib-for-the-Treatment-of-Adults-with-Active-Psoriatic-Arthritis-Accepted-for-Review-Across-Four-Regions-Globally/default.aspx

Bristol Myers Squibb Presents Late-Breaking Data from Pivotal Phase 3 POETYK PsA-1 Trial Demonstrating Superiority of Sotyktu (deucravacitinib) Compared with Placebo in Adults with Psoriatic Arthritis. News release. Bristol Myers Squibb. June 11, 2025.

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Key Takeaways on Inhibiting Structural Damage in Psoriatic Arthritis

In the management of psoriatic arthritis, preventing structural damage and long-term disability is a crucial goal. However, formal treatment guidelines typically emphasize the elimination of active inflammation rather than structural damage inhibition as a primary target. The current treat-to-target approach focuses on controlling swollen joints, reducing inflammatory markers, and managing clinical symptoms. Incorporating advanced imaging techniques such as ultrasound to detect synovitis and enthesitis could provide more sensitive and earlier indicators of disease activity, potentially improving patient outcomes by guiding timely therapeutic adjustments before irreversible damage occurs.

Structural damage assessment is recognized as important but is often considered a secondary domain within clinical trials and treatment strategies. This is partly due to the slow and gradual progression of joint damage in psoriatic arthritis, which can make it difficult to measure within the time frame and size of typical early-phase studies. Although larger and longer trials attempt to evaluate radiographic progression, challenges remain in interpreting these outcomes due to minimal change in placebo groups and ethical constraints on prolonged placebo use. Nonetheless, there is an expectation that structural damage should be evaluated as part of the overall clinical development and management of the disease, albeit not necessarily as a routine treat-to-target end point.

The current era offers unprecedented therapeutic options for psoriatic arthritis, with many treatments providing both efficacy and improved safety profiles. This has transformed patient care, moving away from older, less targeted therapies toward more precise and tolerable interventions. The continued evolution of treatment strategies calls for better surrogate outcome measures, such as imaging-based markers of inflammation and early damage, to be recognized by regulatory agencies. Early identification and intervention remain key to preventing irreversible joint damage, highlighting the importance of educating health care providers and patients alike about timely diagnosis and treatment initiation.

Experts discuss the evolving management of psoriatic arthritis, emphasizing that while current treat-to-target guidelines prioritize controlling inflammation over structural damage, integrating advanced imaging for earlier detection and advocating for structural damage assessment as a key outcome could enhance long-term patient outcomes amid expanding therapeutic options.

Differentiating Between IL-23 Inhibitors in Psoriatic Disease

From a clinical and mechanistic standpoint, both medications target the IL-23 p19 subunit but differ structurally, which may influence their clinical effects. One is fully human with a wild-type Fc backbone that can bind to CD64, a high-affinity receptor found on myeloid cells producing IL-23. This binding potentially allows the drug to localize directly to inflamed sites, enhancing its ability to neutralize IL-23 where it is most active. The other drug is humanized with an Fc region mutation designed to silence immune recognition, which might reduce immune system engagement but may limit its ability to concentrate at inflammation sites. These differences could explain variations in clinical efficacy, such as stronger effects on structural damage or symptom improvement seen in some study data.

Clinically, these mechanistic distinctions translate into potential practical benefits. For example, one medication’s dosing flexibility—with options to shorten intervals for heavier or biologically experienced patients—may help manage breakthrough symptoms more effectively. Although head-to-head trials are lacking, numerical trends suggest subtle differences in outcomes such as ACR scores and fatigue, with radiographic inhibition being a key differentiator. Meanwhile, the other agent’s radiographic data have not shown statistical significance, partly due to minimal disease progression in the trial population, leaving some uncertainty about its effectiveness in preventing joint damage.

Assessing structural progression in psoriatic arthritis is inherently challenging because changes are slow and may not appear in placebo groups over typical trial durations. Moreover, evolving ethical standards limit the length of placebo-controlled phases, complicating data collection. In this context, innovative imaging tools such as ultrasound—which can detect erosions earlier and more sensitively—may offer valuable surrogate end points to better evaluate treatment effects on joint damage moving forward.

Experts discuss the structural and mechanistic differences between 2 IL-23 p19 inhibitors, exploring how variations in Fc region design may influence their localization to inflamed sites and clinical efficacy—particularly in preventing structural damage—and highlight challenges in assessing progression in psoriatic arthritis trials, suggesting that advanced imaging such as ultrasound could improve future evaluations.

Guselkumab and Structural Damage Inhibition in Psoriatic Arthritis: Insights from the APEX Trial

Recent advances in clinical research have provided critical clarity around the ability of IL-23 inhibitors to inhibit structural damage in psoriatic arthritis, a key concern for clinicians considering long-term outcomes. Early trials such as DISCOVER-2 initially suggested promise, but the approved every-8-week dose of one agent narrowly missed statistical significance in halting radiographic progression. This uncertainty led to the development of a larger, more targeted study—the APEX trial—which focused on bio-naive patients with evidence of existing joint damage. Results showed that both dosing regimens significantly inhibited structural progression, providing much-needed reassurance for clinicians.

For years, many prescribers hesitated to consider IL-23 inhibitors first line for joint disease, despite their clear effectiveness in skin clearance. With the APEX data now confirming structural protection, clinicians can confidently consider these agents even for patients with more aggressive or erosive disease. This is particularly impactful given that IL-23 inhibitors offer notable advantages in safety and dosing convenience. The ability to protect joints while minimizing serious adverse effect concerns and maintaining a low-frequency dosing schedule has the potential to shift prescribing patterns, especially for patients prioritizing long-term joint function and quality of life.

The favorable safety profile of IL-23 inhibitors also streamlines patient counseling. Discussions can often be shorter and more reassuring, as concerns commonly associated with other biologic classes—such as TB reactivation, depression, or cancer risk—are not prominent in the IL-23 data. Although some safety protocols such as TB testing remain in place for insurance reasons, clinical experts increasingly see these agents as both effective and low risk. As dermatologists and rheumatologists gain more confidence from robust evidence, the role of IL-23 inhibitors as a legitimate first-line option for both skin and joint involvement is expected to grow substantially.

Experts discuss recent clinical evidence confirming that IL-23 inhibitors effectively inhibit structural damage in psoriatic arthritis—particularly highlighted by the APEX trial’s findings in bio-naive patients—reinforcing their emerging role as a safe, convenient, and increasingly preferred first-line treatment for both joint and skin manifestations.

Philip J. Mease, MD

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