Clinical improvement in psoriasis with specific targeting of interleukin-23

Tamara Kopp; Elisabeth Riedl; Christine Bangert; Edward P Bowman; Elli Greisenegger; Ann Horowitz; Harald Kittler; Wendy M Blumenschein; Terrill K McClanahan; Thomas Marbury; Claus Zachariae; Danlin Xu; Xiaoli Shirley Hou; Anish Mehta; Anthe S Zandvliet; Diana Montgomery; Frank van Aarle; Sauzanne Khalilieh

doi:10.1038/nature14175

Clinical improvement in psoriasis with specific targeting of interleukin-23

Tamara Kopp, Elisabeth Riedl, Christine Bangert, Edward P Bowman, Elli Greisenegger, Ann Horowitz, Harald Kittler, Wendy M Blumenschein, Terrill K McClanahan, Thomas Marbury, Claus Zachariae, Danlin Xu, Xiaoli Shirley Hou, Anish Mehta, Anthe S Zandvliet, Diana Montgomery, Frank van Aarle, Sauzanne Khalilieh

Institut for Klinisk Medicin

141 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	521
Udgave nummer	7551
Sider (fra-til)	222-6
Antal sider	5
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature14175
Status	Udgivet - 14 maj 2015

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10.1038/nature14175

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Kopp, T., Riedl, E., Bangert, C., Bowman, E. P., Greisenegger, E., Horowitz, A., Kittler, H., Blumenschein, W. M., McClanahan, T. K., Marbury, T., Zachariae, C., Xu, D., Hou, X. S., Mehta, A., Zandvliet, A. S., Montgomery, D., van Aarle, F., & Khalilieh, S. (2015). Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature, 521(7551), 222-6. https://doi.org/10.1038/nature14175

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, S 2015, 'Clinical improvement in psoriasis with specific targeting of interleukin-23', Nature, bind 521, nr. 7551, s. 222-6. https://doi.org/10.1038/nature14175

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title = "Clinical improvement in psoriasis with specific targeting of interleukin-23",

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.",

keywords = "Adolescent, Adult, Aged, Antibodies, Monoclonal, Double-Blind Method, Epithelium, Gene Expression Regulation, Humans, Immunotherapy, Interleukin-23, Middle Aged, Molecular Targeted Therapy, Protein Subunits, Psoriasis, Skin, Treatment Outcome, Young Adult",

author = "Tamara Kopp and Elisabeth Riedl and Christine Bangert and Bowman, {Edward P} and Elli Greisenegger and Ann Horowitz and Harald Kittler and Blumenschein, {Wendy M} and McClanahan, {Terrill K} and Thomas Marbury and Claus Zachariae and Danlin Xu and Hou, {Xiaoli Shirley} and Anish Mehta and Zandvliet, {Anthe S} and Diana Montgomery and {van Aarle}, Frank and Sauzanne Khalilieh",

year = "2015",

month = may,

day = "14",

doi = "10.1038/nature14175",

language = "English",

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pages = "222--6",

journal = "Nature",

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T1 - Clinical improvement in psoriasis with specific targeting of interleukin-23

AU - Kopp, Tamara

AU - Riedl, Elisabeth

AU - Bangert, Christine

AU - Bowman, Edward P

AU - Greisenegger, Elli

AU - Horowitz, Ann

AU - Kittler, Harald

AU - Blumenschein, Wendy M

AU - McClanahan, Terrill K

AU - Marbury, Thomas

AU - Zachariae, Claus

AU - Xu, Danlin

AU - Hou, Xiaoli Shirley

AU - Mehta, Anish

AU - Zandvliet, Anthe S

AU - Montgomery, Diana

AU - van Aarle, Frank

AU - Khalilieh, Sauzanne

PY - 2015/5/14

Y1 - 2015/5/14

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal

KW - Double-Blind Method

KW - Epithelium

KW - Gene Expression Regulation

KW - Humans

KW - Immunotherapy

KW - Interleukin-23

KW - Middle Aged

KW - Molecular Targeted Therapy

KW - Protein Subunits

KW - Psoriasis

KW - Skin

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1038/nature14175

DO - 10.1038/nature14175

M3 - Letter

C2 - 25754330

SN - 0028-0836

VL - 521

SP - 222

EP - 226

JO - Nature

JF - Nature

IS - 7551

ER -

Clinical improvement in psoriasis with specific targeting of interleukin-23

Abstract

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