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Deucravacitinib: TYK2 Inhibitor for Psoriasis

Deucravacitinib is an oral medication approved for the treatment of moderate to severe plaque psoriasis in adults. It selectively inhibits the enzyme tyrosine kinase 2 (TYK2).

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Things worth knowing about "Deucravacitinib"

Deucravacitinib is an oral medication approved for the treatment of moderate to severe plaque psoriasis in adults. It selectively inhibits the enzyme tyrosine kinase 2 (TYK2).

What is Deucravacitinib?

Deucravacitinib is a prescription medication approved for the treatment of moderate to severe plaque psoriasis in adults. It belongs to a novel class of drugs known as TYK2 inhibitors and is taken once daily as an oral tablet. In the United States, it is marketed under the brand name Sotyktu and received approval from the U.S. Food and Drug Administration (FDA) in 2022. In the European Union, it was approved by the European Medicines Agency (EMA).

Indication

Deucravacitinib is indicated for the treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy. It is suitable for patients who have had an inadequate response to, or are intolerant of, other systemic therapies, including biologics.

Mechanism of Action

Deucravacitinib works by selectively and allosterically inhibiting the enzyme tyrosine kinase 2 (TYK2). TYK2 is a member of the Janus kinase (JAK) family and plays a key role in transmitting signals from certain cytokines, particularly:

Interleukin-12 (IL-12)
Interleukin-23 (IL-23)
Type I interferons

These signaling molecules are central drivers of the excessive immune response that causes skin inflammation and the characteristic scaling seen in psoriasis. By blocking TYK2, deucravacitinib interrupts these signaling pathways and reduces skin inflammation.

Unlike other JAK inhibitors (e.g., tofacitinib, baricitinib), deucravacitinib does not bind to the active catalytic site of the enzyme but rather to a regulatory domain (pseudokinase domain). This allosteric binding gives the drug greater selectivity for TYK2 and is intended to reduce the risk of off-target side effects associated with the inhibition of other JAK enzymes.

Dosage and Administration

The recommended dose is 6 mg once daily as an oral tablet, taken with or without food. No dose adjustment is generally required. Deucravacitinib is not approved for use in children and adolescents under 18 years of age.

Side Effects

Like all medications, deucravacitinib can cause side effects. The most common side effects observed in clinical trials include:

Upper respiratory tract infections (e.g., common cold, nasopharyngitis)
Folliculitis (inflammation of hair follicles)
Elevated cholesterol levels (hypercholesterolaemia)
Diarrhoea
Skin rash
Acne
Oral herpes (herpes simplex)

Rare but potentially serious risks include infections, including opportunistic infections such as tuberculosis. Patients should be tested for latent tuberculosis before starting therapy and should inform their doctor if they develop signs of a severe infection.

Contraindications and Interactions

Deucravacitinib should not be used in:

Patients with known hypersensitivity to the active substance or any excipients
Patients with active tuberculosis or other serious active infections
Pregnant or breastfeeding women (unless the benefit-risk ratio has been carefully assessed)

Relevant interactions have been reported with potent CYP3A4 inducers (e.g., rifampicin), which can accelerate the breakdown of deucravacitinib and reduce its efficacy. Concurrent use with other immunosuppressants or biologics is not recommended.

Clinical Studies

The approval is based on the results of the Phase III studies POETYK PSO-1 and POETYK PSO-2. In these studies, deucravacitinib demonstrated superior efficacy compared to placebo and to apremilast (another oral psoriasis medication), as measured by skin improvement at 16 weeks. A significant proportion of patients achieved a PASI 75 response (at least 75% improvement in psoriasis severity).

References

Armstrong AW et al. - Trial of Deucravacitinib versus Placebo and Apremilast in Plaque Psoriasis. New England Journal of Medicine, 2023.
European Medicines Agency (EMA) - Sotyktu (deucravacitinib): Summary of Product Characteristics. EMA, 2023. Available at: www.ema.europa.eu
U.S. Food and Drug Administration (FDA) - Sotyktu (deucravacitinib) Prescribing Information. FDA, 2022. Available at: www.fda.gov

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