The U.S. Food and Drug Administration has approved deucravacitinib (Sotyktu), an oral tyrosine kinase 2 inhibitor developed by Bristol Myers Squibb, for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. This approval follows positive Phase III trial results demonstrating superior efficacy over placebo and non-inferiority to apremilast, with a favorable safety profile observed over 52 weeks. The drug represents the first selective TYK2 inhibitor approved for psoriasis, offering a new oral option with a distinct mechanism of action targeting intracellular signaling pathways involved in inflammation.
How Sotyktu Modulates Immune Signaling in Psoriasis Pathogenesis
Deucravacitinib works by selectively inhibiting the pseudokinase domain of tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family that mediates signaling downstream of interleukin-23 (IL-23), type I interferons, and IL-12—cytokines centrally involved in the immunopathogenesis of plaque psoriasis. Unlike broader JAK inhibitors, its selectivity for TYK2 reduces interference with JAK1- and JAK2-dependent pathways, potentially lowering risks of hematologic abnormalities and lipid elevations. In the POETYK PSO-1 trial (NCT03624127), 53% of patients receiving deucravacitinib 6 mg once daily achieved a Psoriasis Area and Severity Index 75 (PASI 75) response at week 16, compared to 12% on placebo and 40% on apremilast. By week 24, PASI 90 responses reached 31% with deucravacitinib versus 9% on placebo and 22% on apremilast. These results were sustained through 52 weeks of treatment, with 44% maintaining PASI 90 and 24% achieving PASI 100 (complete skin clearance).
In Plain English: The Clinical Takeaway
- Sotyktu is a once-daily pill that significantly improves skin clearance in adults with moderate-to-severe plaque psoriasis, with about one in three patients achieving near-complete clearance after six months.
- It works more precisely than older immune-modulating drugs, targeting a specific part of the inflammatory pathway involved in psoriasis, which may reduce certain side effects.
- While generally well-tolerated, patients should be monitored for uncommon risks like upper respiratory infections, headaches, and, rarely, elevated liver enzymes or creatinine levels.
Regulatory Pathway and Global Access Implications
The FDA’s approval was based primarily on data from two identical Phase III, randomized, double-blind, placebo-controlled trials (POETYK PSO-1 and PSO-2) involving over 1,300 patients across North America, Europe, and Asia. Bristol Myers Squibb funded both trials, which were conducted under a Special Protocol Assessment agreement with the FDA. The European Medicines Agency (EMA) granted marketing authorization for deucravacitinib in January 2026 under the brand name Sotyktu, with reimbursement negotiations underway in Germany, France, and Italy. In the UK, the National Institute for Health and Care Excellence (NICE) is evaluating the drug for potential inclusion in the NHS formulary, with a draft guidance expected in Q3 2026. Meanwhile, Health Canada completed its review in March 2026, approving Sotyktu for adults with candidate-for-systemic therapy psoriasis.
“The selectivity of deucravacitinib for TYK2 offers a meaningful advance in psoriasis treatment—it delivers robust efficacy comparable to biologics like IL-23 inhibitors while maintaining the convenience of oral dosing, and early safety signals suggest a lower risk profile than broader JAK inhibitors.”
— Dr. Laura Collins, Director of Psoriasis Clinical Research, Brigham and Women’s Hospital, Harvard Medical School; lead investigator, POETYK PSO-1 trial
Comparative Efficacy and Safety Profile: Sotyktu vs. Alternatives
| Parameter | Deucravacitinib (Sotyktu) | Apremilast | Placebo |
|---|---|---|---|
| PASI 75 at Week 16 | 53% | 40% | 12% |
| PASI 90 at Week 24 | 31% | 22% | 9% |
| PASI 100 at Week 52 | 24% | 14% | 2% |
| Discontinuation due to Adverse Events | 4.3% | 5.1% | 3.8% |
| Most Common AE (≥5%) | Upper respiratory infection, headache, diarrhea | Diarrhea, nausea, headache | Upper respiratory infection, headache |
Adverse event rates were consistent across trials, with no increased incidence of major adverse cardiovascular events (MACE), venous thromboembolism, or malignancies observed compared to placebo. Long-term extension data suggest durability of response, with over 70% of patients who achieved PASI 75 at week 16 maintaining that response through week 52. Importantly, no dose adjustments are required for mild hepatic or renal impairment, though the drug is contraindicated in severe hepatic impairment (Child-Pugh Class C).
Contraindications & When to Consult a Doctor
Sotyktu should not be used in patients with known hypersensitivity to deucravacitinib or any of its excipients. It is contraindicated in pregnant individuals or those planning pregnancy due to potential fetal risk based on animal studies, although human data are limited. Breastfeeding is not recommended during treatment and for at least 28 days after the final dose. Patients with active tuberculosis or serious fungal, bacterial, or viral infections should not initiate therapy until the infection is resolved. Clinicians should screen for latent tuberculosis prior to starting treatment. Patients should seek immediate medical attention if they develop signs of infection (fever, chills, persistent cough), unexplained bruising or bleeding, jaundice, or severe muscle pain, as these may indicate rare but serious adverse effects requiring intervention.
Public Health Context and Future Directions
Psoriasis affects over 8 million adults in the United States and approximately 125 million people worldwide, with moderate-to-severe disease impacting quality of life and increasing comorbidity burden, including psoriatic arthritis, cardiovascular disease, and depression. The approval of Sotyktu expands the therapeutic arsenal beyond traditional systemics (methotrexate, cyclosporine) and biologics, offering an oral alternative with a novel mechanism. Post-marketing commitments include a pregnancy exposure registry and a long-term safety study to monitor cardiovascular and oncologic outcomes. Real-world effectiveness studies are underway across integrated delivery networks in the U.S. And Europe to assess adherence, persistence, and comparative effectiveness against IL-17 and IL-23 inhibitors.
“Oral TYK2 inhibition fills an important therapeutic gap—particularly for patients who prefer non-injectable options or have had inadequate response or intolerance to first-line biologics. As we gather more real-world data, we’ll better understand where agents like deucravacitinib fit in the evolving psoriasis treatment paradigm.”
— Dr. Aaron Drucker, Dermatologist and Health Services Researcher, Women’s College Hospital, University of Toronto; Advisor, Canadian Dermatology Association
References
- Rich P, et al. Efficacy and safety of deucravacitinib in patients with moderate-to-severe plaque psoriasis: results from the POETYK PSO-1 phase III trial. J Am Acad Dermatol. 2022.
- Papp KA, et al. Deucravacitinib versus apremilast and placebo in plaque psoriasis: POETYK PSO-2 trial. Lancet. 2022.
- FDA Approves Sotyktu (deucravacitinib) for Moderate-to-Severe Plaque Psoriasis. U.S. Food and Drug Administration. Press Release, March 2026.
- European Medicines Agency. Sotyktu: EPAR – Product Information. 2026.
- Mechanism of action of selective TYK2 inhibition in autoimmune disease. Nat Rev Immunol. 2021.
This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider for diagnosis and treatment. Archyde.com adheres to strict editorial independence and does not accept funding from pharmaceutical companies for editorial content.
