POS1040 SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR: AS ASSESSED BY LABORATORY PARAMETERS – RESULTS FROM A PHASE 2 TRIAL IN PSORIATIC ARTHRITIS AND 2 PHASE 3 TRIALS IN PSORIASIS

Abstract

Background: Deucravacitinib (DEUC) is a novel, oral, selective, allosteric tyros‐ine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA,1 and vs PBO or apremilast in 2 Phase 3 PsO trials.2 Objectives: To assess the effects of DEUC on multiple laboratory parameters through the frst 16 weeks of treatment (PBO‐controlled) in these trials. Methods: The Phase 2 double‐blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double‐blind PsO trials, POETYK PSO‐1 and POETYK PSO‐2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspar‐tate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed. Results: In the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC‐, PBO‐, and apremilast‐treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms. Conclusion: DEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two‐thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO.