Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor that inhibits cytokine signaling in psoriasis pathogenesis.
Deucravacitinib showed superiority to apremilast and placebo treating adult patients with moderate-to-severe plaque psoriasis, according to data from the phase 3 POETYK trial published in the Journal of the American Academy of Dermatology. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, limits cytokine signaling in psoriasis pathogenesis and could fill a significant unmet need in patients with the dermatologic condition.
“Current therapies for plaque psoriasis, including biologics and small-molecule oral agents, are generally efficacious but physicians often have to choose between efficacy, safety, and patient convenience when recommending treatments,” the study authors wrote. “Therefore, novel, oral-targeted therapies that are more efficacious, well tolerated, and convenient to administer are needed.”
The study authors sought to investigate data from the 2 prior POETYK trials, which found that for both plaque psoriasis and psoriatic arthritis, deucravacitinib showed significantly greater efficacy than placebo. The investigators designed the PSO-2 trial to be a placebo and active comparator-controlled, randomized, multi-center, double-blind study.
The study enrolled 1020 adult patients with plaque psoriasis, 18 years of age or older. Inclusion criteria included a static Physician's Global Assessment (sPGA) score of ≥3, a Psoriasis Area and Severity Index (PASI) rating of ≥12, and body surface area involvement of ≥10% for ≥6 months prior to recruitment. Further, 1020 study participants who were previously administered some type of therapy for their psoriasis were still recruited if they had a washout period between the end of therapy and study initiation.
From June 2018 to November 2019, the study authors randomized patients 2:1:1, with 6 mg of deucravacitinib or placebo administered daily or 30 mg of apremilast administered twice per day. Participants were also randomized with a stratification by geographic area (United States vs the rest of the world), prior biologic exposure for inflammatory conditions such as psoriasis, and body weight (≥90 kg vs <90 kg).
By week 16 of the POETYK PSO-2 study, the primary endpoint was achieved with deucravacitinib showing significantly higher percentages for both sPGA scores (49.5% vs 8.6%; P<.0001) and PASI 75 scores (53.0% vs 9.4%; P<.0001) at week 16 week.
The study authors also found that response rates for the listed outcomes increased through 24 weeks, noting responses were higher for deucravacitinib compared to apremilast at both week 16 and 24. The investigators found that deucravacitinib was associated with higher PASI 90, PASI 100, and sPGA 0 responses after 16 weeks compared to placebo and to apremilast (P ≤.0051).
Deucravacitinib also showed superiority to apremilast in PASI 90 scores after 24 weeks (32.5% vs 19.7%; P = .0001), with PASI 75 responses maintained through 52 weeks. Median time to loss of PASI 75 in patients who were rerandomized to placebo was 85 days. However, median time to relapse could not be determined because <50% of patients relapsed through week 52 following deucravacitinib withdrawal.
Rates of adverse events (AE) were similar across cohorts during both assessment periods. From weeks 0-16, nasopharyngitis and upper respiratory tract infection were the most common AEs in the deucravacitinib cohort. Headache, diarrhea, and nausea were more common in apremilast-treated patients. There were no new safety signals identified from weeks 16-52 vs weeks 0-16.
Incidences of serious AEs were also low and similar across cohorts. The rates of AE-related discontinuations were lower in the deucravacitinib cohort compared with the placebo and apremilast cohorts.
“In POETYK PSO-2, deucravacitinib was superior to placebo and apremilast and provided clinically meaningful improvements over 52 weeks in multiple efficacy measures,” the study authors wrote. “The overall safety profile of deucravacitinib, including a slight increase in the risk of nonserious viral infections, appears to be consistent with the mechanism of selective TYK2 inhibition.”
Strober, B. et al. (2023) “Deucravacitinib versus Placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of TYK2 inhibitor psoriasis second trial,” Journal of the American Academy of Dermatology, 88(1), pp. 40–51. Available at https://doi.org/10.1016/j.jaad.2022.08.061. Accessed January 19, 2023.