Abstract:
: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-being. 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.
journal_name
Naturejournal_title
Natureauthors
Kopp T,Riedl E,Bangert C,Bowman EP,Greisenegger E,Horowitz A,Kittler H,Blumenschein WM,McClanahan TK,Marbury T,Zachariae C,Xu D,Hou XS,Mehta A,Zandvliet AS,Montgomery D,van Aarle F,Khalilieh Sdoi
10.1038/nature14175subject
Has Abstractpub_date
2015-05-14 00:00:00pages
222-6issue
7551eissn
0028-0836issn
1476-4687pii
nature14175journal_volume
521pub_type
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