Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Evaluation of Creatine Phosphokinase Elevations in the Phase 3 POETYK PSO-1 and PSO-2 Trials

Abstract

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In the phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials, deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated. This pooled safety analysis of POETYK PSO-1 and PSO-2 assessed changes from baseline in creatine phosphokinase (CPK) levels and CPK elevations and rhabdomyolysis adverse events (AEs) in patients receiving placebo, deucravacitinib, or apremilast.

Methods: 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. Shifts from baseline in severity grade (Common Terminology Criteria for Adverse Events [CTCAE] version 5) of CPK levels were analyzed. Elevated CPK and rhabdomyolysis adverse events (AEs) were reported.

Results: The pooled population included 1683 patients (placebo, n=419; deucravacitinib, n=842; apremilast, n=422). At baseline, the proportions of patients with grade ≥1 CPK levels were comparable (placebo, 6.3%; deucravacitinib, 5.9%; apremilast, 7.4%). During Weeks 0-16, worsening of CPK levels by >1 CTCAE grade from baseline occurred at similar rates in patients receiving placebo (2.2%), deucravacitinib (2.5%), and apremilast (1.4%). Most deucravacitinib-treated patients maintained their baseline CPK CTCAE grade or shifted to a lower grade through Week 52. Elevated CPK AEs were reported in 1.2% (placebo), 2.7% (deucravacitinib), and 0.7% (apremilast) of patients through Week 16. Exposure-adjusted incidence rates (EAIRs) of elevated CPK AEs through Week 52 were comparable across treatments (placebo, 4.5/100 person-years [PY]; deucravacitinib, 4.7/100 PY; apremilast, 3.6/100 PY). Two deucravacitinib-treated patients (0.2/100 PY) and 1 apremilast-treated patient (0.4/100 PY) discontinued due to AEs of asymptomatic elevated CPK. Two deucravacitinib-treated patients had rhabdomyolysis with potential inciting events, one of which was associated with CPK elevation.

Conclusion: Most deucravacitinib-treated patients maintained their baseline CPK grade or shifted to a lower grade through Weeks 16 and 52. The EAIR of CPK elevation AEs were comparable across treatment groups over 52 weeks.