Deucravacitinib

What is deucravacitinib?

Deucravacitinib is an oral, selective tyrosine kinase 2 (TYK2) inhibitor for the systemic treatment of moderate to severe
plaque psoriasis and other immune-mediated diseases.

What is deucravacitinib used for?

Deucravacitinib (SOTYKTU™) was first approved in September 2022 by the US Food and Drug Administration (FDA) and subsequently in the European Union (EU) for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Deucravacitinib was later approved in Japan for treatment of plaque psoriasis, generalised pustular psoriasis, and erythrodermic psoriasis.

Chronic plaque psoriasis 

Chronic plaque psoriasis 

Thick scale overlying plaques of psoriasis on the leg 

Further clinical trials are underway to explore the efficacy of deucravacitinib for treatment of other immune-mediated diseases such as:

• Crohn disease and ulcerative colitis
• Cutaneous lupus erythematosus
• Discoid lupus erythematosus
• Systemic lupus erythematosus (SLE)
• Psoriatic arthritis
• Sjögren syndrome.

How does deucravacitinib work?

Deucravacitinib is the first in a new class of oral, selective tyrosine kinase 2 (TYK2) inhibitors.

TYK2 is an intracellular enzyme and part of the Janus kinase (JAK) family. The JAK family is essential for cytokine signalling.

While JAK inhibitors competitively bind to the catalytic domain, which is highly conserved across the JAK family, deucravacitinib allosterically binds the regulatory domain unique to TYK2, thus driving its selectivity for TYK2 without inhibiting JAK1/2/3 at clinically relevant doses.

The precise mechanism of action explaining the link between TYK2 inhibition and therapeutic effectiveness of deucravacitinib is currently unknown.

It is postulated that TYK2 pairs with other Janus kinase enzymes to mediate signalling of various pro-inflammatory cytokines eg, interleukin-23 (IL-23), IL-12, and Type I interferons (IFNα/β).

What are the precautions and contraindications with deucravacitinib?

Precautions

• Pregnancy and breastfeeding — currently no safety information available; benefits of use during pregnancy or lactation should be balanced against potential risks
• Concurrent treatment with other potent immunosuppressants (eg, azathioprine, cyclosporine, tacrolimus) — safety of deucravacitinib in combination with such agents has not been evaluated; concurrent use is not recommended by the manufacturer
• History of recurrent infections or underlying conditions that predispose to infection
• Exposure to tuberculosis
• History of serious or opportunistic infections
• Known malignancy
• Administration of live vaccines during treatment (see: Immunisation in immunosuppressed dermatology patients)

Contraindications

• Hypersensitivity to deucravacitinib or its excipients
• Clinically important active infections eg, tuberculosis (TB) or hepatitis B or C.
• Severe hepatic impairment (Child-Pugh C)

Deucravacitinib administration and monitoring

Deucravacitinib is a systemic therapy taken as a once-daily oral tablet.

Monitoring:

• Monitor for signs of infection before initiating and during treatment
• Pretreatment screening for hepatitis B and C, and latent tuberculosis
• Serum triglycerides periodically
• Liver function tests (LFTs) at baseline and periodically in patients with known or suspected liver disease
• Creatine kinase (if myopathy suspected).

What are the benefits of deucravacitinib?

• Convenient administration: Oral medication taken at any time of day, with or without food.
• Favourable safety profile: Demonstrated favourable safety profile compared to traditional JAK inhibitors, likely due to its selectivity for TYK2.
• Benefits may be seen as early as one week into treatment (however, may not be significant).
• Moderate-severe plaque psoriasis: Demonstrated superior efficacy in adults compared to apremilast and placebo.
  • The POETIC PSO-2 phase III study found 53% deucravacitinib, 40% apremilast, and 9% placebo of patients showed a ≥75% reduction in their Psoriasis Area and Severity Index (PASI) score after 16 weeks.
• Scalp and fingernail psoriasis: Evidence from phase III trials supports the use of deucravacitnib scalp psoriasis and fingernail psoriasis.
• Real-world effectiveness: A real-world study (Northern America) demonstrated the effectiveness of 6 months of continuous treatment in improving skin clearance for plaque psoriasis, as measured by BSA (9.8 to 3.7) and PASI (6.5 to 2.3)

What are the disadvantages of deucravacitinib?

• Risk of severe infections and malignancy as it is an immunomodulator
• Risk of elevation of liver enzymes and triglycerides
• Links to increased risk of rhabdomyolysis
• Relatively expensive, though subsidies are granted in some countries
• Typically takes 4 weeks after initiating treatment to see significant improvements; may take up to 24 weeks to achieve maximal therapeutic efficacy
• Tolerance and efficacy largely dependent on individual patient response

What are the side effects and risks of deucravacitinib?

Clinical trials extending up to 52 weeks have shown that deucravacitinib is generally well tolerated.

Common side effects:

• Nasopharyngitis
• Upper respiratory tract infections
• Headache.

Mucocutaneous side effects:

• Herpes simplex (HSV) infection
• Folliculitis
• Acne
• Aphthous ulcers.

Uncommon side effects:

• Hypertriglyceridemia
• Raised liver enzymes.

Serious adverse events:

• Hepatotoxicity
• Rhabdomyolysis
• Hypersensitivity reaction
• Malignancy
• Serious infections such as tuberculosis.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and [British National Formulary for Children ](http://bnfc.nice.org.uk/ (BNFC).