Deucravacitinib in plaque psoriasis: 2-year laboratory results from the phase 3 POETYK PSO program

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 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 was significantly more efficacious than placebo and apremilast and was well tolerated in moderate to severe plaque psoriasis. PSO-1 and PSO-2 completers could enroll in the ongoing open-label POETYK long-term extension (LTE) trial. Changes in blood laboratory parameters with deucravacitinib in the PSO-1, PSO-2, and LTE trials were compared with signature changes seen with JAK 1/2/3 inhibitors. Methods: The 52-week, double-blind PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials randomized adults with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. At Week 52, eligible patients enrolled in POETYK LTE (NCT04036435) and received deucravacitinib. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) were assessed through Week 100 (LTE Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were evaluated. Results: 1519 patients received ≥1 dose of deucravacitinib in all 3 trials. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure; median duration of exposure was 682.0 days (97 weeks). No trends in clinically meaningful changes from baseline were observed in these parameters from Weeks 0–52 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare, with incidence rates comparable to placebo and apremilast through Week 52; no increases were seen in the LTE. Two patients discontinued deucravacitinib due to lymphopenia and abnormal hepatic function. Conclusion: No trends in clinically meaningful changes from baseline were observed with deucravacitinib in laboratory parameters, including signature changes associated with JAK 1/2/3 inhibitors. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare and comparable to incidence rates seen with placebo and apremilast. These results suggest laboratory monitoring is not warranted with deucravacitinib.