Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

Eline de Keyser, Celine I. Busard, Sven Lanssens, Lieve Meuleman, Barbara A. Hutten, Antonio Costanzo, Juul M. van den Reek, Jeffrey Zweegers, Jo Lambert, Phyllis I. Spuls

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.
Original languageEnglish
Pages (from-to)634-639
JournalTherapeutic Drug Monitoring
Volume41
Issue number5
DOIs
Publication statusPublished - 2019

Cite this

de Keyser, Eline ; Busard, Celine I. ; Lanssens, Sven ; Meuleman, Lieve ; Hutten, Barbara A. ; Costanzo, Antonio ; van den Reek, Juul M. ; Zweegers, Jeffrey ; Lambert, Jo ; Spuls, Phyllis I. / Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab. In: Therapeutic Drug Monitoring. 2019 ; Vol. 41, No. 5. pp. 634-639.
@article{f70f3c5aaf8c45aea73c3e0a7c03dd03,
title = "Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab",
abstract = "BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7{\%}) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41{\%} with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.",
author = "{de Keyser}, Eline and Busard, {Celine I.} and Sven Lanssens and Lieve Meuleman and Hutten, {Barbara A.} and Antonio Costanzo and {van den Reek}, {Juul M.} and Jeffrey Zweegers and Jo Lambert and Spuls, {Phyllis I.}",
year = "2019",
doi = "10.1097/FTD.0000000000000646",
language = "English",
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de Keyser, E, Busard, CI, Lanssens, S, Meuleman, L, Hutten, BA, Costanzo, A, van den Reek, JM, Zweegers, J, Lambert, J & Spuls, PI 2019, 'Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab' Therapeutic Drug Monitoring, vol. 41, no. 5, pp. 634-639. https://doi.org/10.1097/FTD.0000000000000646

Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab. / de Keyser, Eline; Busard, Celine I.; Lanssens, Sven; Meuleman, Lieve; Hutten, Barbara A.; Costanzo, Antonio; van den Reek, Juul M.; Zweegers, Jeffrey; Lambert, Jo; Spuls, Phyllis I.

In: Therapeutic Drug Monitoring, Vol. 41, No. 5, 2019, p. 634-639.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

AU - de Keyser, Eline

AU - Busard, Celine I.

AU - Lanssens, Sven

AU - Meuleman, Lieve

AU - Hutten, Barbara A.

AU - Costanzo, Antonio

AU - van den Reek, Juul M.

AU - Zweegers, Jeffrey

AU - Lambert, Jo

AU - Spuls, Phyllis I.

PY - 2019

Y1 - 2019

N2 - BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

AB - BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31107404

U2 - 10.1097/FTD.0000000000000646

DO - 10.1097/FTD.0000000000000646

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EP - 639

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

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