A novel tyrosine kinase 2 (TYK2) inhibitor showed remarkable efficacy as a treatment for psoriasis with one-third of patients reaching a Psoriasis Area and Severity Index (PASI) 100 in the highest dose. The safety profile was acceptable and in line with experiences from earlier trials with TYK2 inhibitors.
TYK2 is a key component in the JAK/STAT signaling pathway, according to April Armstrong, MD, MPH. “By selectively inhibiting TYK2, receptor-mediated activation and downstream signal transduction of immune-related cytokines like IL-6, IL-10, IL-12 and type I interferon can be prevented,” explained Dr. Armstrong, who presented the results of the of the phase 2b, randomized, double-blind, placebo-controlled study at the 2023 American Academy of Dermatology annual meeting1.
A total of 259 patients with moderate-to-severe psoriasis were randomly assigned to receive 1 of 4 doses of this agent or placebo. The percentage of patients who achieved PASI 75 at week 12 was the primary endpoint.
A significantly greater proportion of patients achieved PASI 75 at doses of 5mg or greater (44%, 68%, and 67% with 5 mg, 15 mg, and 30 mg, respectively) versus placebo (6%; P<0.001 for each comparison).
“What we learn from this is that 15 mg and 30 mg were superior to 5 mg, almost 7 out of 10 achieved PASI 75 by week 12,” said Dr. Armstrong. Moreover, 46% of patients achieved PASI 90 with the higher doses, which was assessed as a secondary endpoint. Almost one-third of patients achieved PASI 100 with the highest dose, “an impressive result for an oral agent,” she noted.
COVID-19 infection was the most frequent adverse event as the study was conducted during the pandemic. Adverse event occurred at 53% to 62% with no clear dose dependence in active arms and 44% in placebo. Additionally, participants presented with diarrhea, acne, and folliculitis of the truncal area. Mean lab values and changes from baseline did not reveal adverse trends in cell counts. However, in the high doses, creatine kinase showed some variability.
These promising results support further studies of the TYK2 inhibitor in psoriasis, Dr. Armstrong said.
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