Publication Date:
2015-03-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- England -- Nature. 2015 May 14;521(7551):222-6. doi: 10.1038/nature14175. Epub 2015 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, 1090 Vienna, Austria. ; Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria. ; Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA. ; Orlando Clinical Research Center, Orlando, Florida 32809, USA. ; Department of Dermato-allergology, Gentofte Hospital, University of Copenhagen, Kildegaardsvej 28, DK-2900 Hellerup, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25754330" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Aged
;
Antibodies, Monoclonal/adverse effects/immunology/pharmacology/*therapeutic use
;
Double-Blind Method
;
Epithelium/drug effects/pathology
;
Gene Expression Regulation/drug effects
;
Humans
;
*Immunotherapy
;
Interleukin-23/*antagonists & inhibitors/chemistry/immunology
;
Middle Aged
;
*Molecular Targeted Therapy
;
Protein Subunits/antagonists & inhibitors/chemistry/immunology
;
Psoriasis/*drug therapy/immunology/metabolism/pathology
;
Skin/drug effects/immunology/metabolism/pathology
;
Treatment Outcome
;
Young Adult
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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