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Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study

BACKGROUND: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of cor...

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Autores principales: Yao, Jia-yin, Zhang, Min, Wang, Wei, Peng, Xiang, Zhao, Jun-zhang, Liu, Tao, Li, Zhi-wei, Sun, Hai-tian, Hu, Pinjin, Zhi, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522105/
https://www.ncbi.nlm.nih.gov/pubmed/34663208
http://dx.doi.org/10.1186/s12876-021-01946-8
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author Yao, Jia-yin
Zhang, Min
Wang, Wei
Peng, Xiang
Zhao, Jun-zhang
Liu, Tao
Li, Zhi-wei
Sun, Hai-tian
Hu, Pinjin
Zhi, Min
author_facet Yao, Jia-yin
Zhang, Min
Wang, Wei
Peng, Xiang
Zhao, Jun-zhang
Liu, Tao
Li, Zhi-wei
Sun, Hai-tian
Hu, Pinjin
Zhi, Min
author_sort Yao, Jia-yin
collection PubMed
description BACKGROUND: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting. METHODS: We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. RESULTS: Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). CONCLUSIONS: UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-021-01946-8.
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spelling pubmed-85221052021-10-21 Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study Yao, Jia-yin Zhang, Min Wang, Wei Peng, Xiang Zhao, Jun-zhang Liu, Tao Li, Zhi-wei Sun, Hai-tian Hu, Pinjin Zhi, Min BMC Gastroenterol Research BACKGROUND: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting. METHODS: We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. RESULTS: Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). CONCLUSIONS: UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-021-01946-8. BioMed Central 2021-10-18 /pmc/articles/PMC8522105/ /pubmed/34663208 http://dx.doi.org/10.1186/s12876-021-01946-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yao, Jia-yin
Zhang, Min
Wang, Wei
Peng, Xiang
Zhao, Jun-zhang
Liu, Tao
Li, Zhi-wei
Sun, Hai-tian
Hu, Pinjin
Zhi, Min
Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title_full Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title_fullStr Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title_full_unstemmed Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title_short Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study
title_sort ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory crohn’s disease: a chinese real-world study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522105/
https://www.ncbi.nlm.nih.gov/pubmed/34663208
http://dx.doi.org/10.1186/s12876-021-01946-8
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