TYK2 Signaling Pathways for Psoriasis

In the pathophysiology of psoriasis, tyrosine kinase 2 (TYK2) signaling pathways are connected; some TYK2 signaling pathways might be effective in treating psoriasis. In a study published in The New England Journal of Medicine, researchers aim to assess how selective TYK2 inhibition affects psoriasis. 

In the phase 2, double-blind trial, the TYK2 inhibitor BMS-986165 was given to adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients (n=267) were randomly assigned to receive 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily, or to receive placebo.  

The percentage of patients at week 12 with a 75% or greater reduction in the PASI score was 7% (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165 every other day (P=0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily (P<0.001 vs. placebo), 69% (31 of 45 patients) with 3 mg twice daily (P<0.001 vs. placebo), 67% (30 of 45 patients) with 6 mg twice daily (P<0.001 vs. placebo), and 75% (33 of 44 patients) with 12 mg daily (P<0.001 vs. placebo) 

Results showed that “selective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a period of 12 weeks” but that more research needed to be completed to determine its safety and durability of effect in patients with psoriasis. 

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