Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study

BADBIR; BSTOP Study Groups; PSORT consortium

doi:10.1016/j.jid.2020.03.957

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study

BADBIR, BSTOP Study Groups, PSORT consortium

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

Original language	English
Pages (from-to)	2129-2137
Number of pages	9
Journal	Journal of Investigative Dermatology
Volume	140
Issue number	11
DOIs	https://doi.org/10.1016/j.jid.2020.03.957
Publication status	Published - Nov 2020

Access to Document

10.1016/j.jid.2020.03.957

Cite this

@article{cdb0c493256b40fba09c1518e34aba51,

title = "Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study",

abstract = "Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.",

author = "BADBIR and {BSTOP Study Groups} and {PSORT consortium} and Loeff, {Floris C.} and Teresa Tsakok and Lisanne Dijk and Hart, {Margreet H.} and Michael Duckworth and David Baudry and Alice Russell and Nick Dand and {van Leeuwen}, Astrid and Christopher Griffiths and Nick Reynolds and Barker, {Jonathan N.W.N.} and Burden, {A. David} and Richard Warren and {de Vries}, Annick and Karien Bloem and Wolbink, {Gerrit Jan} and Smith, {Catherine H.} and Theo Rispens and Marilyn Benham and David Burden and Ian Evans and Christopher Griffiths and Sagair Hussain and Brian Kirby and Linda Lawson and Kayleigh Mason and Kathleen McElhone and Ruth Murphy and Anthony Ormerod and Caroline Owen and Nick Reynolds and Smith, {Catherine H.} and Richard Warren and Barker, {Jonathan N.W.N.} and Barnes, {Michael R.} and Paola DiMeglio and Richard Emsley and Andrea Evans and Katherine Payne and Deborah Stocken",

year = "2020",

month = nov,

doi = "10.1016/j.jid.2020.03.957",

language = "English",

volume = "140",

pages = "2129--2137",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Clinical Impact of Antibodies against Ustekinumab in Psoriasis

T2 - An Observational, Cross-Sectional, Multicenter Study

AU - BADBIR

AU - BSTOP Study Groups

AU - PSORT consortium

AU - Loeff, Floris C.

AU - Tsakok, Teresa

AU - Dijk, Lisanne

AU - Hart, Margreet H.

AU - Duckworth, Michael

AU - Baudry, David

AU - Russell, Alice

AU - Dand, Nick

AU - van Leeuwen, Astrid

AU - Griffiths, Christopher

AU - Reynolds, Nick

AU - Barker, Jonathan N.W.N.

AU - Burden, A. David

AU - Warren, Richard

AU - de Vries, Annick

AU - Bloem, Karien

AU - Wolbink, Gerrit Jan

AU - Smith, Catherine H.

AU - Rispens, Theo

AU - Benham, Marilyn

AU - Burden, David

AU - Evans, Ian

AU - Griffiths, Christopher

AU - Hussain, Sagair

AU - Kirby, Brian

AU - Lawson, Linda

AU - Mason, Kayleigh

AU - McElhone, Kathleen

AU - Murphy, Ruth

AU - Ormerod, Anthony

AU - Owen, Caroline

AU - Reynolds, Nick

AU - Smith, Catherine H.

AU - Warren, Richard

AU - Barker, Jonathan N.W.N.

AU - Barnes, Michael R.

AU - DiMeglio, Paola

AU - Emsley, Richard

AU - Evans, Andrea

AU - Payne, Katherine

AU - Stocken, Deborah

PY - 2020/11

Y1 - 2020/11

N2 - Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

AB - Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

UR - http://www.scopus.com/inward/record.url?scp=85085618809&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2020.03.957

DO - 10.1016/j.jid.2020.03.957

M3 - Article

AN - SCOPUS:85085618809

SN - 0022-202X

VL - 140

SP - 2129

EP - 2137

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 11

ER -

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study

Abstract

Access to Document

Other files and links

Fingerprint

Cite this