• Kim Papp, Kenneth Gordon, Diamant Thaçi, Akimichi Morita, Melinda Gooderham, Peter Foley, Ihab G Girgis, Sudeep Kundu, and Subhashis Banerjee.
• From K. Papp Clinical Research and Probity Medical Research, Waterloo (K.P.), the SKiN Centre for Dermatology and Probity Medical Research, Peterborough (M.G.), and Queen's University, Kingston (M.G.) - all in Ontario, Canada; Medical College of Wisconsin, Milwaukee (K.G.); the University of Luebeck, Luebeck, Germany (D.T.); Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan (A.M.); the University of Melbourne, St. Vincent's Hospital Melbourne, Skin and Cancer Foundation, and Probity Medical Research, Melbourne, VIC, Australia (P.F.); and Bristol-Myers Squibb, Princeton, NJ (I.G.G., S.K., S.B.).
• N. Engl. J. Med. 2018 Oct 4; 379 (14): 1313-1321.

BackgroundTyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis.MethodsWe conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in 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 were randomly assigned to receive the drug orally at a dose of 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 primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis).ResultsA total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients 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). There were three serious adverse events in patients receiving the active drug, as well as one case of malignant melanoma 96 days after the start of treatment.ConclusionsSelective 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. Larger and longer-duration trials of this drug are required to determine its safety and durability of effect in patients with psoriasis. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02931838 .).

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