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Nature. 2015 May 14;521(7551):222-6. doi: 10.1038/nature14175. Epub 2015 Mar 9.

Clinical improvement in psoriasis with specific targeting of interleukin-23.

Author information

1
1] Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria [2] Juvenis Medical Center, 1010 Vienna, Austria.
2
Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, 1090 Vienna, Austria.
3
Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria.
4
Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
5
Orlando Clinical Research Center, Orlando, Florida 32809, USA.
6
Department of Dermato-allergology, Gentofte Hospital, University of Copenhagen, Kildegaardsvej 28, DK-2900 Hellerup, Denmark.

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.

PMID:
25754330
DOI:
10.1038/nature14175
[Indexed for MEDLINE]
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