Deucravacitinib in moderate to severe plaque psoriasis: liver transaminase results from the phase 3 POETYK PSO program

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the phase 3 POETYK PSO-1 and PSO-2 trials, deucravacitinib treatment did not result in clinically meaningful changes across multiple laboratory parameters, including liver transaminases and bilirubin. The current analysis assessed changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the pooled POETYK PSO-1 and PSO-2 population over 16 weeks. Methods: In POETYK PSO-1 and PSO-2, patients with moderate to severe plaque psoriasis were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Patients randomized to placebo crossed over to deucravacitinib at Week 16 in both trials. This analysis uses data from POETYK PSO-1 and PSO-2 pooled by treatment group from Weeks 0-16. ALT and AST were evaluated as mean levels over time, shifts from baseline in Common Terminology Criteria for Adverse Events (CTCAE version 5.0) severity grade, and fold-increase from upper limit of normal (ULN). Patient-level data were evaluated for those who experienced an elevation ≥3´ ULN for ALT or AST in the first 16 weeks of treatment. Results: The pooled POETYK PSO-1 and PSO-2 population included placebo (n=419), deucravacitinib (n=842), and apremilast (n=422). ALT and AST results were available for 413, 833, and 419 patients, respectively. Mean levels of ALT and AST did not change over 16 weeks in any treatment arm. Shifts upwards ≥2 CTCAE grades from baseline in ALT and AST over Weeks 0-16 occurred at a low frequency overall; rates were comparable in patients treated with deucravacitinib (ALT, 0.4%; AST, 0.5%), apremilast (ALT, 0.5%; AST, 0.5%), and placebo (both ALT and AST, 0%). In addition, ALT and AST elevations ≥3´ ULN were infrequent (ALT: placebo 1.2%, deucravacitinib 1.1%, apremilast 0.5%; AST: placebo 0.5%, deucravacitinib 1.6%, apremilast 0.7%). Almost all ALT or AST elevations ≥3´ the ULN between baseline and Week 16 were transient and/or could be traced to underlying liver conditions or concomitant medications. Conclusion: Treatment with deucravacitinib, apremilast, or placebo led to increases in ALT or AST levels from baseline over 16 weeks in a few patients; the increases that did occur were potentially related to underlying liver dysfunction, alcohol use, or use of concomitant medications.