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TYK2, deucravacitinib, plaque psoriasis
Introduction: Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates signaling of cytokines (eg, interleukin-23, Type I interferons) involved in psoriasis pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 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 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), deucravacitinib was significantly more effective vs placebo and apremilast based on multiple endpoints. This study compared efficacy of deucravacitinib vs apremilast over 24 weeks in mean Psoriasis Area and Severity Index (PASI) improvements and evaluated absolute PASI thresholds with continuous deucravacitinib treatment from Day 1 through 52 weeks in PSO-1.
Methods: PSO-1 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily; patients randomized to placebo and apremilast switched to deucravacitinib at Week 16 and Week 24, respectively. Mean change from baseline in PASI and proportions of patients achieving absolute PASI thresholds of ≤1, ≤2, ≤3, ≤4, and ≤5 were evaluated at Week 24 (deucravacitinib vs apremilast) and Week 52 (deucravacitinib only).
Results: Mean baseline PASI was similar in both groups (deucravacitinib, 21.8; apremilast, 21.4). Significantly greater mean percent reductions from baseline in PASI were observed with deucravacitinib vs apremilast at Week 24 (−77.1% vs −50.2%; P < 0.0001); mean reduction in the deucravacitinib group was maintained through Week 52 (−78.4%). Higher proportions of patients receiving deucravacitinib vs apremilast, respectively, achieved absolute PASI thresholds of ≤1 (31.3% vs 12.5%), ≤2 (41.3% vs 21.4%), ≤3 (54.8% vs 28.0%), ≤4 (63.3% vs 33.3%), and ≤5 (68.7% vs 35.7%) at Week 24 (nominal P < 0.0001 for all); response rates were maintained through Week 52 with deucravacitinib (31.3%, 45.5%, 54.5%, 61.4%, and 66.0%, respectively).
Conclusions: Deucravacitinib treatment was associated with clinically meaningful PASI outcomes that were superior to apremilast over 24 weeks and maintained through 52 weeks in patients with moderate to severe plaque psoriasis.
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