Background/Purpose: Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates IL-23, IL-12, and IFNα/β signaling. Deucravacitinib is a novel, oral selective inhibitor of TYK2 acting via the TYK2 regulatory domain. In a Phase 2 trial in patients with active PsA, the primary endpoint, ACR 20 response at Week (Wk) 16, was met and deucravacitinib was well tolerated versus placebo (PBO).¹ This analysis further evaluated improvements in musculoskeletal disease manifestations in patients in the Phase 2 PsA trial.

Methods: This Phase 2 trial (NCT03881059) enrolled patients who had a PsA diagnosis for ≥6 months, fulfilled Classification Criteria for Psoriatic Arthritis, had active disease (≥3 tender joints, ≥3 swollen joints, CRP ≥3 mg/L), and had at least 1 active skin lesion. Patients either failed or were intolerant to ≥1 NSAID, corticosteroid, conventional synthetic DMARD, and/or 1 TNF inhibitor (TNFi; ≤30%). Patients were randomized 1:1:1 to deucravacitinib 6 mg QD or 12 mg QD or PBO, and stratified by TNFi status (experienced vs naive) and body weight (< 90 vs ≥90 kg). The current prespecified subgroup analysis assessed the likelihood of achieving ACR 20 response at Wk 16 based on study stratification factors. A post hoc analysis evaluated mean change from baseline (BL) to Wk 16 in ACR components (tender joint count, swollen joint count, Physician’s Global Assessment of PsA, Patients’ Global Assessment of disease activity, Patients’ Global Assessment of pain, high-sensitivity CRP [hCRP], and HAQ-DI score). Analyses were descriptive using data as observed.

Results: Of 203 patients randomized, 180 (89%) completed 16 wks of treatment (deucravacitinib 6 mg QD, 63/70 [90%]; deucravacitinib 12 mg QD, 59/67 [88%]; PBO, 58/66 [88%]). Demographic and BL disease characteristics were similar across groups. Mean age was 49.8 years and median PsA duration since diagnosis was 4.5 years. Patients treated with deucravacitinib were numerically more likely to achieve ACR 20 response at Wk 16 compared with PBO-treated patients regardless of TNFi experience or body weight, although some of these groups were small (Figure). Improvements for deucravacitinib 6 mg and 12 mg QD versus PBO were observed in all ACR components (Table), with apparent separation occurring as early as Wk 4 on, for example, HAQ-DI (mean change from BL, -0.2 vs -0.2 vs -0.1, respectively) and hCRP (mean change from BL, -7.4 vs -5.2 vs 0.3, respectively), and maintained through Wk 16. No serious adverse events, including serious infections, herpes zoster infection, opportunistic infections, malignancies, or thromboembolic events, were reported in any deucravacitinib treatment group.

Conclusion: Analyses confirmed the efficacy of deucravacitinib versus PBO across TNFi and body weight subgroups. With deucravacitinib treatment, improvements were displayed in all ACR components.

Reference: 1. Mease PJ et al. Presented at the 2020 ACR Convergence, American College of Rheumatology; Nov 5-9, 2020.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-deucravacitinib-an-oral-selective-tyrosine-kinase-2-inhibitor-in-musculoskeletal-manifestations-of-active-psa-in-a-phase-2-randomized-double-blind-placebo-controlled-trial/