BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine 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.2ObjectivesTo assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials.MethodsThe 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], aspartate 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.ResultsIn 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.Table 1.Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16PsA Phase 2PsO Phase 3aCTCAE TermGradePlacebo (n=66)n (%)DEUC 6 mg QD (n=70)n (%)DEUC 12 mg QD (n=67)n (%)Placebo (n=419)n (%)DEUC 6 mg QD (n=842)n (%)Apremilast 30 mg BID (n=422)n (%)BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16Lymphocyte count decreased340000001 (1.4)00000001 (0.2)0001 (0.1)00000Neutrophil count decreased34000000000000001 (0.2)01 (0.1) 01 (0.1)00000Platelet count decreased34000000000000000000000000Anaemia340N/A0N/A0N/A0N/A0N/A0 N/A0N/A0N/A0N/A0 N/A0N/A1 (0.2) N/AAlanine aminotransferase increased34000 000000 0000 0000000000 0Aspartate aminotransferase increased34000000000 01 (1.6)0000 00 01 (0.1)0001 (0.2) 0CPK increased34001 (1.5) 0000 00001 (1.6)1 (0.2) 03 (0.7) 1 (0.2)1 (0.1) 05 (0.6) 6 (0.7)1 (0.2)02 (0.5) 1 (0.2)Cholesterol high3400000000000 00 00 00 00 00000Hypertriglyceridemia34000 01 (1.4) 1 (1.4)2 (2.9) 1 (1.4)1 (1.6) 04 (6.0) 02 (0.5) 1 (0.2)6 (1.5) 04 (0.5)1 (0.1)12 (1.5)2 (0.2)3 (0.7) 08 (2.0) 0aPOETYK PSO-1 and PSO-2 pooled data.BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week.ConclusionDEUC 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.