Commentary: Deucravacitinib Versus Placebo and Apremilast in Moderate to Severe Plaque Psoriasis: Efficacy and Safety Results from the 52-week, Randomized, Double-blinded, Placebo-controlled Phase 3 POETYK PSO-1 Trial

Psoriasis is a heterogeneous disease, and while a range of treatment options are currently available for managing moderate to severe psoriasis, including several classes of biologic drugs, there have been limited options for oral treatment beyond the classic systemic agents (methotrexate, acitretin, and cyclosporin). This article compares deucravacitinib, a novel, selective TYK2 inhibitor, against apremilast, a PDE4 inhibitor and a widely used, relatively recent option for treating psoriasis.

TYK2 is part of the JAK family of tyrosine kinases, which also includes JAK1-3. TYK2 is involved in the transmembrane signaling of key psoriasis-associated cytokines, including IL-12, IL-23, and type I interferons. Unlike other JAK inhibitors, which target the active kinase domain, deucravacitinib targets the pseudokinase domain of TYK2, which gives it high selectivity and may also limit side effects and toxicity. In this randomized, double-blinded study, the efficacy and safety of deucravacitinib were compared to placebo and apremilast in adults with moderate to severe plaque psoriasis. At week 16, PASI 75 (greater than 75% improvement in psoriasis from baseline) was achieved in 58.4% of the patients on deucravacitinib, compared to 35.1% in patients given apremilast and 12.7% of patients on placebo. Similarly, patients treated with deucravacitinib experienced significant improvement in quality-of-life measures and other symptoms, including scalp psoriasis. Deucravacitinib efficacy improved up to 24 weeks of therapy and was maintained through week 52. Treatment was well tolerated, with adverse event rates similar across all three treatment groups, and did not increase during 52 weeks. The most common adverse events in deucravacitinib-treated patients were upper respiratory tract infections. Moreover, no clinically significant laboratory changes were observed.

This head-to-head study of deucravacitinib against apremilast demonstrates its superiority to apremilast. The question arises, where will deucravacitinib fit in the treatment algorithms in real clinical practice now that the FDA has recently approved it for managing moderate to severe psoriasis? While the trial results are promising, this drug’s positioning in clinical practice will require additional studies. This includes data on long-term efficacy and safety beyond 52 weeks (ongoing study) and the impact of a treatment interruption(s). In addition, comparative studies against biologics may be informative; however, based on historical efficacy data, the efficacy of deucravacitinib is likely inferior to anti-IL-17 and anti-IL-23 biologics. While this study provides some insight, clear guidance regarding the placing of deucravacitinib in the context of available treatments cannot yet be given. Still, this will become clear with further evidence and optimally additional head-to-head studies.