학술논문
Clinical improvement in psoriasis with specific targeting of interleukin-23.
Document Type
Article
Author
Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine; Bowman, Edward P.; Greisenegger, Elli; Horowitz, Ann; Kittler, Harald; Blumenschein, Wendy M.; McClanahan, Terrill K.; Marbury, Thomas; Zachariae, Claus; Xu, Danlin; Hou, Xiaoli Shirley; Mehta, Anish; Zandvliet, Anthe S.; Montgomery, Diana; van Aarle, Frank; Khalilieh, Sauzanne
Source
Subject
*PSORIASIS treatment
*MONOCLONAL antibodies
*INTERLEUKIN-23
*CLINICAL drug trials
*SKIN disease genetics
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Language
ISSN
0028-0836
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. [ABSTRACT FROM AUTHOR]