Selective TYK2 Inhibitor (Allosteric — Regulatory Domain Binding) Pregnancy: Avoid — insufficient human data; animal reproductive toxicity studies required before use in pregnancy.

Deucravacitinib (TYK2 Inhibitor — Psoriatic Arthritis/Psoriasis)

Brand names: Sotyktu

Adult dose

Dose: 6 mg oral once daily

Route: Oral

Frequency: Once daily

Max: 6 mg/day

Selective allosteric TYK2 inhibitor — binds to TYK2 regulatory (pseudokinase) domain, not the catalytic domain, providing exquisite selectivity (100-1000× more selective for TYK2 vs JAK1/2/3). Inhibits IL-12, IL-23, and type I IFN signalling. MHRA approved for plaque psoriasis (2023). Phase 3 POETYK PsA trial for psoriatic arthritis completed (positive data expected 2024).

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment required for mild-moderate renal impairment. Severe impairment: no specific guidance.

Hepatic

No dose adjustment for mild-moderate hepatic impairment. Severe: avoid (limited data).

Clinical pearls

POETYK PSO-1/PSO-2 trials (Armstrong et al. NEJM 2023): deucravacitinib 6 mg vs placebo and apremilast — PASI 75 at 16 weeks: 58.4% vs 12.7% (placebo) and 34.4% (apremilast). Superior to apremilast across all endpoints; well-tolerated
Safety advantage vs JAK inhibitors: deucravacitinib's allosteric mechanism (regulatory domain binding) means NO ATP-competitive binding — unlike JAK1/2/3 inhibitors (tofacitinib, baricitinib, upadacitinib). FDA did not apply JAK-class black box warnings (VTE, MACE, malignancy) to deucravacitinib due to distinct mechanism. No clinical signal of VTE or cardiovascular events in POETYK trials
TYK2 pathway selectivity: TYK2 mediates IL-12 and IL-23 signalling (key psoriasis cytokines) plus type I IFN — deucravacitinib's selectivity means targeted immunosuppression without the broad JAK inhibition (which also hits EPO, growth hormone, prolactin receptor signalling)

Contraindications

Active TB (screen before starting)
Severe hepatic impairment
Pregnancy (insufficient data — use contraception)

Side effects

Upper respiratory tract infections (nasopharyngitis, sinusitis)
Oral herpes (cold sores — TYK2 inhibition reduces type I IFN antiviral defence)
Elevated LFTs (mild, usually transient)
Acne-like folliculitis
No significant thrombosis or CV signal (distinguishes from JAK inhibitors — FDA/MHRA did not add JAK-class black box warnings to deucravacitinib)

Interactions

Strong CYP1A2 inhibitors (fluvoxamine — increases deucravacitinib levels; use with caution)
CYP1A2 inducers (smoking, rifampicin — reduce deucravacitinib levels)

Monitoring

TB screening (IGRA or Mantoux) before initiation
LFTs (baseline and periodically)
Skin response (PASI, IGA scores at 16 and 24 weeks)
Herpes simplex recurrence
Infection signs

Reference: BNFc; BNF 90; Armstrong et al. NEJM 2023 (POETYK PSO-1/PSO-2); MHRA Approval Sotyktu 2023; NICE Appraisal pending; Phase 3 POETYK PsA trial (ongoing). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways