The FDA’s approval of deucravacitinib (Sotyktu; Bristol Myers Squibb) for the treatment of adults with active psoriatic arthritis (PsA), marks the first approval of a tyrosine kinase 2 (TYK2) inhibitor for this indication, reflecting growing interest in TYK2 as a therapeutic target across psoriatic disease.
A novel oral agent targeting a distinct immune pathway, deucravacitinib was previously approved in 2022 for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Its approval for PsA adds a targeted oral option for patients who prefer non-injectable therapies or are not candidates for biologics.
Selective Treatment
Plaque psoriasis, the most common form of psoriasis, is an autoimmune disease characterized by thick, red, scaly plaques and affects approximately 8 million people in the United States and 125 million worldwide.
“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,” explained Philip J. Mease, MD, director of rheumatology research, Providence Swedish Medical Center, and clinical professor at the University of Washington School of Medicine. “New oral, effective first-line treatments are needed.”
Deucravacitinib appears to meet this need. Unlike traditional Janus kinase (JAK) inhibitors, which broadly affect multiple pathways, deucravacitinib selectively inhibits TYK2, a signaling kinase involved in the activity of several cytokines implicated in psoriasis and PsA. 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 may help 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 Details
FDA approval is based on results from the phase three multicenter, randomized controlled trials POETYK PsA-1 and POETYK PsA-2. The former evaluated deucravacitinib versus placebo in 670 adults who were naive to biologic disease-modifying anti-rheumatic drugs (bDMARDs), while the latter included 624 adults who were either naive to bDMARDs or had previously received TNF-alpha inhibitors. POETYK PsA-2 also included a safety reference arm in which patients were randomized to receive apremilast.
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.
At week 16, 54% of patients receiving deucravacitinib 6 mg daily achieved at least 20% improvement in American College of Rheumatology (ACR20) response criteria, compared with 34%-39% of those receiving placebo.
Higher thresholds of response were also observed. 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 including 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.
Health-related quality of life was assessed using the 36-Item Short Form Health Survey (SF-36). Patients treated with deucravacitinib showed improvements in SF-36 Physical Component Summary (PCS) score at Week 16 compared with placebo, along with gains across all four PCS domains: physical functioning, role-physical, bodily-pain, and general health.
The safety findings in PsA were generally consistent with those previously observed in plaque psoriasis trials. 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.
Expanding Treatment Choices
For clinicians managing psoriatic disease, the availability of additional oral options may influence treatment decisions — particularly for patients who prefer non-injectable therapies or have contraindications to biologics.
Advocacy groups have also emphasized the importance of expanding treatment options. The Arthritis Foundation noted that additional oral therapies could help address persistent unmet needs among patients living with both joint and skin manifestations of PsA.
With this approval, TYK2 inhibition enters the rheumatology space 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.
The approval of deucravacitinib includes warnings and precautions such as hypersensitivity reactions, infections (including tuberculosis), malignancy (including lymphoma), rhabdomyolysis with elevated CPK levels, and laboratory abnormalities. As with other immune-modulating therapies, clinicians should consider vaccination status and infection risk prior to treatment.
For clinicians treating psoriatic disease, decisions around incorporating TYK2 inhibition into treatment algorithms will likely depend on patient characteristics, prior therapy exposure, and evolving comparative data with other oral and biologic agents.
Final Thoughts
Ongoing studies will help clarify the long-term safety and durability of response with deucravacitinib, providing clinicians and patients with important insights as TYK2 inhibition becomes an established option in psoriatic disease management.
