Deucravacitinib (Sotyktu) — an oral, selective tyrosine kinase 2 (TYK2) inhibitor — has received FDA approval for the treatment of adults with active psoriatic arthritis (PsA), the drug’s manufacturer Bristol Myers Squibb announced.

The drug is the first TYK2 inhibitor to be approved for treating PsA.

Deucravacitinib was first approved by the FDA in 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It has subsequently been approved for plaque psoriasis in the European Union, China, Japan, and other countries.

Approval is based on the results of the phase 3 multicenter, randomized controlled trials POETYK PsA-1 and POETYK PsA-2. POETYK PsA-1 tested deucravacitinib vs placebo in 670 adults who were naive to biologic disease-modifying anti-rheumatic drugs (bDMARDs), and POETYK PsA-2 tested deucravacitinib vs placebo in 624 adults who were naive to bDMARDs or had previously received TNF-alpha inhibitor treatment. POETYK PsA-2 also included a safety reference arm of patients randomly assigned to receive apremilast.

In both trials after 16 weeks, 54% of patients who received deucravacitinib 6 mg daily reached at least 20% improvement in American College of Rheumatology response criteria, compared with 34%-39% of those who received placebo.

A key secondary outcome, achieving minimal disease activity (MDA) at 16 weeks, was reached by 19% with deucravacitinib vs 10% with placebo (P = .0012) in POETYK PsA-1 and by 26% vs 15%, respectively, in POETYK PsA-2 (P = .0007). MDA is achieved by meeting at least five of these seven criteria: tender joint count ≤ 1, swollen joint count ≤ 1, Psoriasis Activity and Severity Index ≤ 1% or body surface area ≤ 3%, patient pain visual analog scale (VAS) ≤ 15, patient global disease activity VAS ≤ 20, Health Assessment Questionnaire Disability Index ≤ 0.5, and tender entheseal points ≤ 1.

In both trials, patients met the CASPAR (Classification for Psoriatic Arthritis) criteria for PsA, with at least three swollen and three tender joints and had an active or documented history of plaque psoriasis. After 16 weeks of treatment, all patients in both trials received active treatment with deucravacitinib through 52 weeks. 

In its press release announcing the approval of deucravacitinib, Bristol Myers Squibb said that the overall safety profile of the drug in patients with PsA was similar to what has been reported in patients with plaque psoriasis. The most common adverse reactions that occurred at rates of ≥ 1% and greater than in those who received placebo were upper respiratory infections, increased blood creatine phosphokinase, herpes simplex, mouth ulcers, folliculitis, and acne.

The company also noted that deucravacitinib is associated with the following warnings and precautions: hypersensitivity reactions, infections, tuberculosis, malignancy including lymphomas, rhabdomyolysis and elevated creatine phosphokinase, laboratory abnormalities, immunizations, and potential risks related to JAK inhibition.

According to Bristol Myers Squibb, by selectively targeting TYK2, deucravacitinib mediates the signaling of interleukin (IL)-23, IL-12, and type 1 interferons, which are key cytokines involved in the pathogenesis of plaque psoriasis and PsA. Deucravacitinib binds to the regulatory domain of TYK2 at physiologically relevant concentrations, allosterically inhibiting TYK2 and mediating its downstream functions. 

The full prescribing information for deucravacitinib is here.