Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

N D Loft, L Skov, L. Iversen, R. Gniadecki, T N Dam, I Brandslund, Hans Jürgen Hoffmann, M. R. Andersen, R B Dessau, A C Bergmann, Niels Møller Andersen, P S Andersen, S Bank, U Vogel, V Andersen

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Resumé

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (qo0.20). The results suggest that genetic variants related to increased IL-1? levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-? levels may be favorable when treating psoriasis with ustekinumab.

OriginalsprogEngelsk
TidsskriftPharmacogenomics Journal
Vol/bind18
Udgave nummer3
Sider (fra-til)494–500
ISSN1470-269X
DOI
StatusUdgivet - 22. maj 2018

Fingeraftryk

Psoriasis
Single Nucleotide Polymorphism
Psoriatic Arthritis
Interleukin-13
Pharmacogenetics
Tumor Necrosis Factor-alpha
Logistic Models
Regression Analysis
Pharmaceutical Preparations

Citer dette

Loft, N D ; Skov, L ; Iversen, L. ; Gniadecki, R. ; Dam, T N ; Brandslund, I ; Hoffmann, Hans Jürgen ; Andersen, M. R. ; Dessau, R B ; Bergmann, A C ; Møller Andersen, Niels ; Andersen, P S ; Bank, S ; Vogel, U ; Andersen, V. / Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. I: Pharmacogenomics Journal. 2018 ; Bind 18, Nr. 3. s. 494–500.
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title = "Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis",
abstract = "Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (qo0.20). The results suggest that genetic variants related to increased IL-1? levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-? levels may be favorable when treating psoriasis with ustekinumab.",
keywords = "Adalimumab/administration & dosage, Adult, Denmark, Etanercept/administration & dosage, Female, Humans, Infliximab/administration & dosage, Interleukin-1beta/genetics, Lymphocyte Antigen 96/genetics, Male, Membrane Glycoproteins/genetics, Middle Aged, Pharmacogenetics/methods, Polymorphism, Single Nucleotide, Psoriasis/drug therapy, Receptors, Interleukin-1/genetics, Toll-Like Receptor 2/genetics, Toll-Like Receptor 9/genetics, Treatment Outcome, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Ustekinumab/administration & dosage",
author = "Loft, {N D} and L Skov and L. Iversen and R. Gniadecki and Dam, {T N} and I Brandslund and Hoffmann, {Hans J{\"u}rgen} and Andersen, {M. R.} and Dessau, {R B} and Bergmann, {A C} and {M{\o}ller Andersen}, Niels and Andersen, {P S} and S Bank and U Vogel and V Andersen",
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month = "5",
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language = "English",
volume = "18",
pages = "494–500",
journal = "The Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
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Loft, ND, Skov, L, Iversen, L, Gniadecki, R, Dam, TN, Brandslund, I, Hoffmann, HJ, Andersen, MR, Dessau, RB, Bergmann, AC, Møller Andersen, N, Andersen, PS, Bank, S, Vogel, U & Andersen, V 2018, 'Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis', Pharmacogenomics Journal, bind 18, nr. 3, s. 494–500. https://doi.org/10.1038/tpj.2017.31

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. / Loft, N D; Skov, L; Iversen, L.; Gniadecki, R.; Dam, T N; Brandslund, I; Hoffmann, Hans Jürgen; Andersen, M. R.; Dessau, R B; Bergmann, A C; Møller Andersen, Niels; Andersen, P S; Bank, S; Vogel, U; Andersen, V.

I: Pharmacogenomics Journal, Bind 18, Nr. 3, 22.05.2018, s. 494–500.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

AU - Loft, N D

AU - Skov, L

AU - Iversen, L.

AU - Gniadecki, R.

AU - Dam, T N

AU - Brandslund, I

AU - Hoffmann, Hans Jürgen

AU - Andersen, M. R.

AU - Dessau, R B

AU - Bergmann, A C

AU - Møller Andersen, Niels

AU - Andersen, P S

AU - Bank, S

AU - Vogel, U

AU - Andersen, V

PY - 2018/5/22

Y1 - 2018/5/22

N2 - Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (qo0.20). The results suggest that genetic variants related to increased IL-1? levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-? levels may be favorable when treating psoriasis with ustekinumab.

AB - Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (qo0.20). The results suggest that genetic variants related to increased IL-1? levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-? levels may be favorable when treating psoriasis with ustekinumab.

KW - Adalimumab/administration & dosage

KW - Adult

KW - Denmark

KW - Etanercept/administration & dosage

KW - Female

KW - Humans

KW - Infliximab/administration & dosage

KW - Interleukin-1beta/genetics

KW - Lymphocyte Antigen 96/genetics

KW - Male

KW - Membrane Glycoproteins/genetics

KW - Middle Aged

KW - Pharmacogenetics/methods

KW - Polymorphism, Single Nucleotide

KW - Psoriasis/drug therapy

KW - Receptors, Interleukin-1/genetics

KW - Toll-Like Receptor 2/genetics

KW - Toll-Like Receptor 9/genetics

KW - Treatment Outcome

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors

KW - Ustekinumab/administration & dosage

U2 - 10.1038/tpj.2017.31

DO - 10.1038/tpj.2017.31

M3 - Journal article

VL - 18

SP - 494

EP - 500

JO - The Pharmacogenomics Journal

JF - The Pharmacogenomics Journal

SN - 1470-269X

IS - 3

ER -