P120 Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with moderate-to-severe scalp psoriasis: laboratory parameter results of a Phase 3b/4, multicentre, randomized, double-blind, placebo-controlled trial (PSORIATYK SCALP)

Abstract Introduction Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Scalp psoriasis occurs in ∼80% of patients with plaque psoriasis; is associated with itching, pain, and bleeding; disproportionately reduces quality of life; and is challenging to treat with topical agents. The 52 week, Phase 3b/4, double-blind PSORIATYK SCALP trial evaluated deucravacitinib efficacy and safety in patients with moderate-to-severe scalp psoriasis, including those with more limited overall psoriasis; these patients are candidates for systemic therapy according to IPC guidelines. Here, the effect of deucravacitinib on changes in laboratory parameters associated with Janus kinase (JAK) 1,2,3 inhibitors was evaluated. Methods Adults (aged ≥18 years) with moderate-to-severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, PSSI ≥12) and body surface area involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. Changes from baseline in lipid (total cholesterol, triglycerides), chemistry [creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST)], and haematology (lymphocytes, neutrophils, platelets, haemoglobin) parameters in blood were evaluated through Week 16 (primary endpoint). Laboratory parameter adverse events, CTCAE Grade ≥3 laboratory abnormalities, shifts from baseline in severity grade of laboratory abnormalities, and discontinuations due to laboratory abnormalities were evaluated. Results One hundred and fifty-four patients were randomized (placebo, n = 51; deucravacitinib, n = 103). No clinically meaningful mean changes from baseline or placebo were observed in any laboratory parameter, including triglycerides, ALT, and AST, through Week 16. Hypercholesterolaemia was reported in one patient in each group; an elevated liver function test was reported in one patient receiving placebo. Grade ≥3 laboratory abnormalities were rare in both groups (deucravacitinib, Grade 3 triglyceride elevation; placebo, Grade 4 triglyceride elevation). Most deucravacitinib-treated patients maintained their baseline laboratory abnormality grade or shifted to a lower grade. No treatment discontinuations or interruptions were reported due to laboratory abnormalities. No muscle-related events linked to creatine phosphokinase elevations were reported. Conclusions This laboratory parameter profile is consistent with results of the Phase 3 POETYK PSO-1, PSO-2, and long-term extension trials, in which deucravacitinib was safe and well-tolerated in patients with plaque psoriasis, including those with moderate-to-severe scalp psoriasis. Signature laboratory changes commonly seen with JAK1,2,3 inhibitors were not reported with deucravacitinib. These results support the safety profile of once-daily oral deucravacitinib in patients with moderate-to-severe scalp psoriasis including those with more limited overall plaque psoriasis.