Psoriasis is a chronic inflammatory skin disorder that affects approximately 2–3% of the population worldwide and has severe effects on patients’ physical and psychological well-being1,2,3. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg−1 groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg−1 group and 13 out of 14 subjects in the 10 mg kg−1 group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.
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The authors thank E. Marcantonio (Merck & Co., Inc.) for his supervision of research and review of this manuscript and J. Pawlowski (Merck & Co., Inc) for editorial and administrative assistance with this manuscript. This study was funded by Merck & Co., Inc.
T.K. and H.K. and E.R. received research support from Merck & Co., Inc. E.R. received travel support from Merck & Co., Inc., and speaker’s fees, travel support, or served on advisory boards for AbbVie, Novartis, Pfizer, Janssen and Amgen. C.B. received travel support from Merck. C.Z. has served as a scientific consultant for Abbvie, Pfizer, Janssen-Cilag, Merck & Co., Inc., Eli Lilly, Takeda and Novartis and clinical study investigator for AbbVie, Amgen, Eli Lilly, Merck & Co., Inc., Takeda and Novartis. T.M. is an employee of Orlando Clinical Research Center, which was contracted by Merck to conduct the trial. E.P.B., A.H., W.M.B., T.K.M., D.X., X.S.H., A.M., A.S.Z., D.M., F.V.A. and S.K. are current or former employees of Merck & Co., Inc, and may own Merck stock. C.B. and E.G. have no competing interests.
Extended data figures and tables
a, b, Biacore sensorgrams showing the 37 °C binding kinetics of human IL-23 (a) and human IL-12 (b) to immobilized tildrakizumab as a threefold dilution series from 0.091 to 22.2 nM. The association phase was measured for 220 s followed by a dissociation phase measurement for 1,800 s. The affinity of tildrakizumab for IL-23 is ∼300 pM.
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Kopp, T., Riedl, E., Bangert, C. et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 521, 222–226 (2015). https://doi.org/10.1038/nature14175
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