FDA Approves Deucravacitinib as First TYK2 Inhibitor for Psoriatic Arthritis

The therapeutic landscape for psoriatic disease continues to evolve with the recent approval of a novel oral agent targeting a distinct immune pathway. The US FDA has approved deucravacitinib (Sotyktu; Bristol Myers Squibb) for the treatment of adults with active psoriatic arthritis (PsA), marking the first approval of a tyrosine kinase 2 (TYK2) inhibitor for this indication.¹ The drug is developed by Bristol Myers Squibb and had previously been approved in 2022 for adults with moderate to severe plaque psoriasis.²

The new indication reflects growing interest in TYK2 as a therapeutic target across psoriatic disease. Unlike traditional Janus kinase (JAK) inhibitors that broadly affect multiple pathways, deucravacitinib selectively inhibits TYK2, a signaling kinase involved in the activity of several cytokines implicated in psoriasis and PsA, including interleukin-23, interleukin-12, and type I interferons. By binding to the regulatory domain of TYK2 rather than the catalytic domain shared across JAK family kinases, the drug exerts allosteric inhibition and achieves a high degree of selectivity in vitro. This selectivity has been proposed as a way to preserve efficacy while potentially reducing off-target effects associated with broader JAK inhibition, although long-term clinical data will ultimately determine how this translates in practice.

Trial Data Supporting Approval

The approval is based on results from 2 phase 3 randomized trials—POETYK PsA-1 and POETYK PsA-2—which evaluated deucravacitinib 6 mg once daily in adults with active PsA. Both trials were multicenter, double-blind, placebo-controlled studies with a 16-week placebo-controlled phase followed by continued treatment through 52 weeks.

POETYK PsA-1 enrolled 670 patients who were naïve to biologic disease-modifying antirheumatic drugs (bDMARDs). POETYK PsA-2 included 624 patients who were either bDMARD-naïve or had previously received a tumor necrosis factor inhibitor. Participants met CASPAR criteria for PsA and had at least three swollen and three tender joints as well as active or previously documented plaque psoriasis.

In both trials, the primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% improvement response (ACR20) at week 16.

Results demonstrated statistically significant improvements compared with placebo. In POETYK PsA-1, 54% of patients receiving deucravacitinib achieved ACR20 compared with 34% of patients receiving placebo. In POETYK PsA-2, ACR20 responses were observed in 54% of patients receiving deucravacitinib versus 39% in the placebo group.

Higher thresholds of response were also reported. ACR50 responses occurred in 24% versus 14% of patients in PsA-1 and 29% versus 16% in PsA-2 (deucravacitinib vs placebo). ACR70 responses were achieved by 12% versus 5% and 10% versus 5%, respectively.

Minimal disease activity (MDA)—a composite endpoint encompassing joint counts, skin involvement, pain, patient global assessment, function, and enthesitis—was also improved. At week 16, MDA responses were observed in 19% of deucravacitinib-treated patients compared with 10% of placebo in PsA-1, and 26% versus 15% in PsA-2.

Impact on Quality of Life

“PsA is a chronic, progressive autoimmune condition that often involves both the joints and skin. Patients often have trouble moving and staying active and can experience pain in the joints, and tendons, or ligaments,” said Philip J. Mease, MD, director of rheumatology research, Providence Swedish Medical Center, and clinical professor, University of Washington School of Medicine. “New oral, effective first-line treatments are needed. In clinical trials, health-related quality of life was assessed by the 36-Item Short Form Health Survey (SF-36). Patients treated with Sotyktu showed improvements in SF-36 Physical Component Summary (PCS) score at Week 16 compared to placebo (key secondary endpoint).¹ There were also improvements in all four SF-36 PCS domain scale scores: physical functioning, role-physical, bodily-pain, and general health.¹ By aiding in symptom management, Sotyktu could make a meaningful difference for patients.”

In the trials, patients treated with deucravacitinib showed improvements in the Physical Component Summary score of the 36-Item Short Form Health Survey (SF-36) at week 16 compared with placebo. Improvements were also seen across domains related to physical functioning, role limitations due to physical health, bodily pain, and general health.

Psoriatic arthritis is a chronic inflammatory condition affecting joints, entheses, skin, and nails. Up to 30% of patients with psoriasis eventually develop PsA, and the disease is associated with reduced mobility, chronic pain, fatigue, and increased risk of comorbidities. Because both skin and musculoskeletal manifestations contribute to disease burden, therapies that address both components remain a focus of clinical development.

Safety Profile

The safety findings in PsA were generally consistent with those previously observed in plaque psoriasis trials of deucravacitinib. The most common adverse reactions occurring in at least 1% of patients and more frequently than placebo included upper respiratory infections, increased blood creatine phosphokinase (CPK), herpes simplex infections, mouth ulcers, folliculitis, and acne.

Warnings and precautions include hypersensitivity reactions, infections including tuberculosis, malignancy including lymphoma, rhabdomyolysis with elevated CPK levels, and laboratory abnormalities. As with other immune-modulating therapies, clinicians are advised to consider vaccination status and infection risk before initiating treatment.

Expanding the Oral Treatment Landscape

For many clinicians managing psoriatic disease, the availability of additional oral options may influence treatment discussions—particularly for patients who prefer non-injectable therapies or who have contraindications to biologics.

Advocacy groups have also highlighted the importance of expanding treatment choices. The Arthritis Foundation noted that additional oral therapies could help address persistent unmet needs among patients living with the joint and skin manifestations of PsA.

With the approval of deucravacitinib for PsA, TYK2 inhibition now enters the rheumatologic treatment landscape after first establishing a role in dermatology. Ongoing long-term studies and open-label extension trials—some extending to 156 weeks—are expected to further clarify the durability of response and long-term safety profile of this targeted pathway.

For clinicians treating psoriatic disease, the decision to incorporate TYK2 inhibition into therapeutic algorithms will likely depend on patient characteristics, prior therapy exposure, and evolving comparative data with other oral and biologic agents.

References

1. U.S. FDA approves Bristol Myers Squibb’s Sotyktu® (deucravacitinib) for the treatment of adults with active psoriatic arthritis. News release. Bristol Myers Squibb. Published March 6, 2026. Accessed March 9, 2026. https://news.bms.com/news/corporate-financial/2026/U-S--FDA-Approves-Bristol-Myers-Squibbs-Sotyktu-deucravacitinib-for-the-Treatment-of-Adults-with-Active-Psoriatic-Arthritis/default.aspx
2. U.S. Food and Drug Administration approves sotyktu™ (deucravacitinib), oral treatment for adults with moderate-to-severe plaque psoriasis. News release. Bristol Myers Squibb. Published September 9, 2022. Accessed March 9, 2026. https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-Sotyktu-deucravacitinib-Oral-Treatment-for-Adults-with-Moderate-to-Severe-Plaque-Psoriasis/default.aspx