Deucravacitinib

• Plaque Psoriasis
• Moderate to Severe Psoriasis
• Oral Psoriasis Treatment
• TYK2 Inhibitor Therapy

Deucravacitinib is a selective tyrosine kinase 2 (TYK2) inhibitor used for the treatment of moderate to severe plaque psoriasis. This first-in-class oral medication offers a novel mechanism targeting the TYK2 pathway with selectivity that spares other JAK family kinases.

Mechanism of Action

Deucravacitinib selectively inhibits tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family that mediates signaling from IL-23, IL-12, and type I interferons—cytokines critically involved in psoriasis pathogenesis. Unlike other JAK inhibitors that block the ATP-binding site, deucravacitinib binds to the regulatory (pseudokinase) domain of TYK2, which stabilizes the enzyme in an inactive conformation. This allosteric mechanism provides high selectivity for TYK2 over other JAK family members (JAK1, JAK2, JAK3), potentially avoiding the immunosuppression and hematologic effects associated with broader JAK inhibition. By blocking TYK2 signaling, deucravacitinib reduces the inflammatory cascade driving psoriatic skin lesions.

Available Formulations

Deucravacitinib is available as oral tablets in 6 mg strength. The tablets can be taken with or without food. The medication should be stored at room temperature.

Medical Uses

Deucravacitinib is FDA-approved for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Clinical trials (POETYK PSO-1 and PSO-2) demonstrated superior efficacy compared to placebo and apremilast, with high rates of PASI 75 and static Physician's Global Assessment (sPGA) responses. The medication provides a new oral option for patients who prefer not to use or cannot use injectable biologics.

Dosing Guidelines

The recommended dose is 6 mg taken orally once daily. The medication can be taken with or without food at approximately the same time each day. No dose titration is required. Treatment should be discontinued if adequate response is not achieved after 24 weeks. If a dose is missed, it should be taken as soon as remembered unless it is close to the time for the next dose.

Important Safety Information

Deucravacitinib can increase the risk of infections, including serious infections. Treatment should not be started during an active infection. Patients should be monitored for signs and symptoms of infection during and after treatment. The medication can cause elevations in triglycerides and creatine phosphokinase (CPK); lipids and CPK should be monitored. Rhabdomyolysis has been reported. Patients should complete all recommended vaccinations before starting therapy; live vaccines should be avoided during treatment.

Drug Interactions

No specific drug interaction studies have been completed, but deucravacitinib is primarily metabolized by CYP1A2 with contributions from CYP2B6 and CYP3A4. Strong CYP1A2 inhibitors may increase deucravacitinib exposure, though dose adjustment recommendations are not established. Concurrent use with other immunosuppressive biologics or potent immunosuppressants has not been studied and is not recommended. Use with live vaccines should be avoided.

Special Populations

There are no adequate data on deucravacitinib use in pregnant women. Animal studies showed adverse developmental effects at high doses. Females of reproductive potential should consider pregnancy planning and prevention. It is unknown whether deucravacitinib is excreted in human breast milk. Safety and efficacy have not been established in pediatric patients. Clinical trials included patients 65 years and older; no overall differences in safety or efficacy were observed. No dose adjustment is needed for mild to moderate renal impairment or mild hepatic impairment; the medication has not been studied in severe renal impairment, end-stage renal disease, or moderate to severe hepatic impairment.