Bristol-Myers Squibb recently announced that the US Food and Drug Administration (FDA) has approved Sotyktu (deucravacitinib) for the treatment of active psoriatic arthritis (PsA) in adults. This approval expands the drug's indications; the FDA first approved it in 2022 for the treatment of adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy or phototherapy.
Psoriatic arthritis (PsA) is a chronic, immune-mediated, heterogeneous disease with a variety of musculoskeletal and cutaneous manifestations, including inflammatory arthritis, enthesitis (inflammation at the attachment points of tendons or ligaments to bone), dactylitis (swelling of the joints of the fingers and toes), and psoriatic skin and nail lesions. Up to 30% of psoriasis patients will develop PsA. In addition to the physical dysfunction, pain, and fatigue caused by PsA, the disease can significantly impact a patient's mental and physical health. Patients with PsA also have a higher risk of developing serious comorbidities. Sotyktu is an oral, once-daily therapy and the first approved selective tyrosine kinase 2 (TYK2) inhibitor for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. It is designed to selectively target TYK2, thereby modulating the signaling of interleukin (IL)-23, IL-12, and type I interferon (IFN), key cytokines in the pathogenesis of plaque psoriasis and psoriatic arthritis. Sotyktu achieves high selectivity by binding to the regulatory domain of TYK2, thereby allosterically inhibiting TYK2 and modulating its downstream functions.
In vitro studies have shown that Sotyktu is highly selective for TYK2 at physiologically relevant concentrations and does not inhibit JAK1, JAK2, or JAK3. The exact mechanism between TYK2 enzyme inhibition and therapeutic efficacy remains unclear.
The FDA approval was based on positive results from the pivotal Phase 3 clinical trials POETYK PsA-1 (NCT04908202) and POETYK PsA-2 (NCT04908189). These two trials evaluated the efficacy and safety of once-daily administration of 6 mg Sotyktu in adult patients with active psoriatic arthritis.
These two randomized, double-blind, placebo-controlled trials enrolled more than 1200 patients. The POETYK PsA-1 study included 670 patients who had not received prior biologic disease-modifying antirheumatic drugs (bDMARDs), while the POETYK PsA-2 study included 624 patients who had not received bDMARDs or had previously received TNF-α inhibitors.
All participants met the CASPAR diagnostic criteria, having at least three swollen joints and three tender joints, and had active or confirmed plaque psoriasis.
In both trials, Sotyktu treatment significantly improved disease activity compared to placebo. The primary endpoint was defined as the proportion of patients achieving the American College of Rheumatology 20 (ACR20) criteria for remission at week 16, and key secondary endpoints including minimum disease activity (MDA) remission.
In addition to improvements in joint disease activity, patients receiving Sotyktu also showed improvements in health-related quality of life. In clinical trials, compared to placebo, the therapy improved the SF-36 Comprehensive Physical Function Score at week 16, with improvements across multiple domains including physical function, physical limitations, body pain, and overall health.
The overall safety profile of Sotyktu observed in patients with active psoriatic arthritis was substantially consistent with that in patients with plaque psoriasis. The most common adverse events (occurring ≥1% in the Sotyktu group and higher than in the placebo group) included: upper respiratory tract infection, elevated serum creatine phosphokinase, herpes simplex, oral ulcers, folliculitis, and acne. Sotyktu is associated with the following warnings and precautions: hypersensitivity reactions, infections, tuberculosis, malignancies (including lymphoma), rhabdomyolysis and elevated creatine phosphokinase (CPK), abnormal laboratory tests, immunization, and potential risks associated with JAK suppression.
