Deucravacitinib, a selective oral TYK2 inhibitor, achieved significant and consistent improvements across all seven components of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA), according to findings from a phase 2 trial published in Rheumatology (Oxford). The post-hoc analysis highlighted a comprehensive therapeutic response, reinforcing the potential of TYK2 inhibition in addressing the multifaceted nature of PsA.
The randomized trial included 203 patients assigned to receive either placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg once daily. At baseline, while some patients met thresholds for individual MDA components, none achieved the full composite MDA criteria. Treatment with deucravacitinib over 16 weeks led to numerically greater reductions in disease activity across all MDA components compared to placebo. By week 16, a higher proportion of patients receiving deucravacitinib, regardless of dose met the criteria for each MDA component, including improvements in joint counts, skin disease, pain, patient global assessment, physical function, and enthesitis. The responses were comparable between the two deucravacitinib doses, indicating effective disease modulation at both 6 mg and 12 mg once daily.
Understanding of PsA pathophysiology has advanced markedly in recent years, with growing evidence that cytokines, particularly those signaling through tyrosine kinase 2 (TYK2), such as IL-23, play a key role in driving the disease. TYK2, a member of the Janus kinase (JAK) family, is essential for intracellular signaling of key pro-inflammatory cytokines. Unlike traditional JAK inhibitors that target the active kinase domain, deucravacitinib selectively binds to the regulatory pseudokinase domain of TYK2. This binding induces a conformational change that locks TYK2 in an inactive state, offering greater selectivity over JAK1, JAK2, and JAK3. By specifically inhibiting cytokines such as IL-12, IL-23, and type I interferons, central to the pathogenesis of psoriasis and other immune-mediated diseases, deucravacitinib offers a targeted therapeutic approach with potentially fewer adverse effects than broader immunosuppressive agents.
Deucravacitinib, the first oral selective allosteric TYK2 inhibitor approved for the treatment of psoriasis, also holds promise for a range of other immune-mediated diseases. Emerging evidence supports its potential efficacy in conditions such as psoriatic arthritis (PsA), palmoplantar pustulosis (PPP), systemic lupus erythematosus (SLE), Sjögren’s disease (SjD), and inflammatory bowel disease (IBD), highlighting its broad applicability in targeting immune pathways across diverse clinical settings.
The study findings support the notion that deucravacitinib’s mechanism of action, as a selective allosteric TYK2 inhibitor, contributes to broad clinical benefits in PsA. As longer-term data from ongoing phase 3 trials become available, further clarity is expected on the durability and scope of deucravacitinib’s impact in psoriatic arthritis. For now, these phase 2 results mark a meaningful step forward in TYK2 inhibition as a novel treatment strategy for PsA.
References
- Kavanaugh A, Coates LC, Mease PJ, Nowak M, Hippeli L, Lehman T, et al. Deucravacitinib, a selective, TYK2 inhibitor, in psoriatic arthritis: achievement of minimal disease activity components in a phase 2 trial. Rheumatology. 2025 May 1;64(5):2557–64.
- Bang CH, Park CJ, Kim YS. The Expanding Therapeutic Potential of Deucravacitinib Beyond Psoriasis: A Narrative Review. Journal of Clinical Medicine. 2025 Jan;14(5):1745.