- Warren RB. Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: 52-week efficacy results from the phase 3 POETYK PSO-1 and POETYK PSO-2 trials. D1T01.4C, EADV Congress 2021, 29 Sept–2 Oct.
Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates the signalling of cytokines IL-23, IL-12, and type I interferons all involved in psoriasis pathogenesis. The small molecule deucravacitinib selectively inhibits TYK2 via an allosteric mechanism by uniquely binding to the regulatory domain rather than to the more conserved active domain where JAK 1/2/3 inhibitors bind.
In the 2 global phase 3 studies, POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), deucravacitinib was significantly more efficacious than placebo and apremilast based on the coprimary endpoint of Psoriasis Area and Severity Index improvement by 75% (PASI 75) and static Physicians Global Assessments clear or almost clear skin (PGA 0/1) at week 16. Both studies included patients with moderate-to-severe psoriasis. The agent was also well tolerated.
To evaluate the long-term efficacy of deucravacitinib, all participants in the PSO-1 study were switched after the double-blind phase (at week 16) from placebo to deucravacitinib and treated until week 52. Assessed were the maintenance of efficacy on continued treatment or switch from placebo to deucravacitinib at week 16 and durability of response through week 52.
Responses achieved at week 16 were maintained to week 52 in patients who received continuous deucravacitinib treatment. “The non-responder imputation analysis is the most conservative analysis we have, but still patients showed a good maintenance of response,” Prof. Richard Warren (University of Manchester, UK) explained. A PASI 90 response was achieved by 35.5% of patients at week 16 and 44.0% at week 52.
Similarly, the sPGA 0/1 results of week 16 (53.6%) were maintained through 52 weeks (52.7%). Patients who switched from placebo to deucravacitinib at week 16 achieved comparable PASI 75 and sPGA 0/1 responses to those observed in patients who received continuous deucravacitinib treatment. The agent also showed good efficacy in scalp psoriasis. At the end of the PSO-1 study, more than 40% of patients achieved a quality of life no longer impaired by the disease.
In the PSO-2 trial, at week 24, PASI 75 responders were either re-randomised to deucravacitinib and treated until week 52, or re-randomised to placebo (random withdrawal analysis). PASI 75 and sPGA 0/1 responses were also maintained on continuous treatment through week 52 in most patients. “In the random withdrawal analysis, we detected an impressive maintenance of response, ” Prof. Warren said. Of the patients who switched from deucravacitinib to placebo at week 24, 31.3% showed a PASI 75 response at 52 weeks. The median time to loss of PASI 75 response was 12 weeks.
These results showed that deucravacitinib, a once-daily oral drug, has the potential to become an efficacious and well-tolerated treatment choice for patients with moderate-to-severe psoriasis.