General Information

Sotyktu (deucravacitinib) is a tyrosine kinase 2 (TYK2) inhibitor.

Sotyktu is specifically indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Sotyktu is supplied as a tablet for oral administration. 

• Evaluate patients for active and latent tuberculosis (TB) infection prior to initiating treatment. If positive, start treatment for TB prior to Sotyktu administration.
• Update immunizations according to current immunization guidelines

The recommended dosage of Sotyktu is 6 mg taken orally once daily, with or without food.

• Do not crush, cut, or chew the tablets

Mechanism of Action

Sotyktu (deucravacitinib) is a selective, allosteric inhibitor of tyrosine kinase 2 (TYK2). TYK2 is a member of the Janus kinase (JAK) family. Sotyktu binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme. This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of Signal Transducers and Activators of Transcription (STATs) as shown in cell-based assays. Janus kinases function as pairs of homo- or heterodimers in the JAK-STAT pathways. TYK2 pairs with JAK1 to mediate multiple cytokine pathways and also pairs with JAK2 to transmit signals as shown in cell-based assays. The precise mechanism linking inhibition of TYK2 enzyme to therapeutic effectiveness in the treatment of adults with moderate-to-severe plaque psoriasis is not currently known.

Side Effects

Adverse effects associated with the use of Sotyktu may include, but are not limited to, the following:

• upper respiratory infections
• blood creatine phosphokinase increased
• herpes simplex
• mouth ulcers
• folliculitis
• acne

Clinical Trial Results

The FDA approval was based on the phase 3 POETYK PSO-1 and POETYK PSO-2 trials which evaluated the safety and efficacy of Sotyktu (6 mg once daily) compared to placebo and Otezla (apremilast) (30 mg twice daily) in patients with moderate-to-severe plaque psoriasis. Both were multi-national, multi-center, randomized, double-blind, placebo- and active comparator-controlled 52-week Phase 3 studies. POETYK PSO-2 included a randomized withdrawal and retreatment period after Week 24. In total, 664 patients were enrolled in POETYK PSO-1 and 1,020 patients were enrolled in POETYK PSO-2.

The co-primary endpoints of both POETYK PSO-1 and POETYK PSO-2 were the percentage of patients who achieved Psoriasis Area and Severity Index 75 (PASI75) and the percentage of patients who achieved static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) at Week 16 versus placebo.

In POETYK PSO-1 the rates were PASI75: Sotyktu (58%), placebo (13%) and Otezla (35%) and sPGA 0/1: Soyyktu (54%), placebo (7%) and Otezla (32%). In POETYK PSO-2 the rates were PASI75: Sotyktu (53%), placebo (9%) and Otezla (40%) and sPGA 0/1: Soyyktu (50%), placebo (9%) and Otezla (34%).

Key secondary endpoints. which included the percentage of patients who achieved PASI 75, PASI 90 and sPGA 0/1 compared to Otezla at Week 16 and Week 24, also demonstrated superiority over placebo and Otezla.

Responses persisted through Week 52, as 82% (187/228) of patients who achieved PASI 75 with Sotyktu at Week 24 maintained their response at Week 52 in POETYK PSO-1. In POETYK PSO-2, 80% (119/148) of patients who continued on Sotyktu maintained PASI 75 response compared to 31% (47/150) of patients who were withdrawn from Sotyktu.