The orally available, selective tyrosine kinase-2 inhibitor deucravacitinib met the primary and all secondary endpoints and improved quality of life in a randomized, double-blind, placebo-controlled phase 2 trial that included 180 patients with active psoriatic arthritis. The treatment was well tolerated and the safety profile was consistent with that observed in an earlier phase 2 trial.
Deucravacitinib (formerly BMS-986165) is a novel oral tyrosine kinase (TYK)2 inhibitor. It is far more selective than other drugs in this class, as it doesn’t bind to the kinase domain, but only to a regulatory domain of TYK2 outside the active site [1]. Thus, it inhibits downstream pathways important in psoriasis and psoriatic arthritis (PsA) pathophysiology, including interleukin (IL)-23 and IL-22, while limiting off-target effects observed with other kinase inhibitors.
In an earlier phase 2 dose-finding study in psoriasis, this drug showed to be significantly more effective compared with placebo: 67-75% of patients treated with ≥3 mg deucravacitinib achieved a ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at 12 weeks (vs 7% with placebo; P<0.001) with only mild-to-moderate adverse events.
In the trial presented during the meeting, the efficacy and safety of the selective TYK2-inhibitor were evaluated in patients with active PsA, results from the initial 16-week placebo-controlled phase were presented.
The 16 weeks of treatment were completed by 180 of 203 patients (89%). Baseline characteristics were comparable between all groups. An inadequate response to TNF inhibitors was observed in 15% of patients. Both deucravacitinib 6 and 12 mg demonstrated significantly greater ACR 20 responses (primary endpoint) versus placebo (52.9% and 62.7% versus 31.8%, respectively). The selective TYK2 inhibitor was also superior regarding ACR 50 and ACR 70 improvement. Significant results were observed regardless of previous TNF inhibitor exposure or body weight (<90 kg vs ≥90 kg). In addition, functional improvements (assessed in the Health Assessment Questionnaire–Disability Index) were significantly more pronounced in both deucravacitinib doses compared with placebo. Moreover, the treatment led to an increased quality of life and a resolution of enthesitis, while psoriasis-related and composite outcomes were improved versus placebo.
The treatment was generally well tolerated with a safety profile consistent with that observed in the earlier psoriasis trial. “These results suggest that deucravacitinib may be a promising treatment for patients with active PsA and support its continued clinical development for this disease,” Prof. Philip J. Mease (University of Washington, USA) concluded.
- Mease PJ, et al. Efficacy and safety of deucravacitinib (BMS-986165), an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: results from a phase 2, randomized, double-blind placebo controlled trial. L03, ACR Convergence 2020 Virtual Annual Meeting, 5-9 November 2020.
