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Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease

Monitoring of anti-drug antibodies in patients on ustekinumab is not routinely recommended in patients with inflammatory bowel disease (IBD) due to low rates of immunogenicity. Aim of study: The purpose of this study was to investigate the relationship between anti-drug antibodies detected by a drug...

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Autores principales: Roblin, Xavier, Duru, Gérard, Papamichael, Konstantinos, Cheifetz, Adam S., Kwiatek, Sandy, Berger, Anne-Emmanuelle, Barrau, Mathilde, Waeckel, Louis, Nancey, Stephane, Paul, Stephane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219534/
https://www.ncbi.nlm.nih.gov/pubmed/37240501
http://dx.doi.org/10.3390/jcm12103395
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author Roblin, Xavier
Duru, Gérard
Papamichael, Konstantinos
Cheifetz, Adam S.
Kwiatek, Sandy
Berger, Anne-Emmanuelle
Barrau, Mathilde
Waeckel, Louis
Nancey, Stephane
Paul, Stephane
author_facet Roblin, Xavier
Duru, Gérard
Papamichael, Konstantinos
Cheifetz, Adam S.
Kwiatek, Sandy
Berger, Anne-Emmanuelle
Barrau, Mathilde
Waeckel, Louis
Nancey, Stephane
Paul, Stephane
author_sort Roblin, Xavier
collection PubMed
description Monitoring of anti-drug antibodies in patients on ustekinumab is not routinely recommended in patients with inflammatory bowel disease (IBD) due to low rates of immunogenicity. Aim of study: The purpose of this study was to investigate the relationship between anti-drug antibodies detected by a drug-tolerant assay and loss of response (LOR) to therapy in a cohort of patients with IBD being treated with ustekinumab. Patients and Methods: This retrospective study consecutively enrolled all adult patients with moderate to severe active IBD who had at least 2 years of follow-up after ustekinumab was initiated. LOR was defined as CDAI > 220 or HBI > 4 for Crohn’s disease (CD) and partial Mayo subscore > 3 for ulcerative colitis (UC) and with a modification in disease management. Results: Ninety patients were included (78 CD and 12 UC; mean age 37 years). Median levels of anti-ustekinumab antibodies (ATU) were significantly higher in patients with LOR compared to those with ongoing clinical response (15.2 µg/mL-eq CI (7.9–21.5) and 4.7 µg/mL-eq CI (2.1–10.5), respectively; p = 0.04). The area under the ROC curve (AUROC) for ATU in predicting LOR was 0.76. The optimal cut-off point for identifying patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80% and specificity of 85%. Uni- and multivariate analyses showed that serum ATU ≥ 9.5 µg/mL-eq (hazard ratio (HR) 2.54, 95%CI (1.80–5.93)), p = 0.022, prior vedolizumab (HR 2.78, 95%CI (1.09–3.34), p = 0.019) and prior azathioprine (HR 0.54, 95%CI (0.20–0.76), p = 0.014) exposures were the only factors independently associated with LOR to UST. Conclusion: In our real-life cohort, ATU was identified as an independent predictor of LOR to ustekinumab in patients with IBD.
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spelling pubmed-102195342023-05-27 Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease Roblin, Xavier Duru, Gérard Papamichael, Konstantinos Cheifetz, Adam S. Kwiatek, Sandy Berger, Anne-Emmanuelle Barrau, Mathilde Waeckel, Louis Nancey, Stephane Paul, Stephane J Clin Med Article Monitoring of anti-drug antibodies in patients on ustekinumab is not routinely recommended in patients with inflammatory bowel disease (IBD) due to low rates of immunogenicity. Aim of study: The purpose of this study was to investigate the relationship between anti-drug antibodies detected by a drug-tolerant assay and loss of response (LOR) to therapy in a cohort of patients with IBD being treated with ustekinumab. Patients and Methods: This retrospective study consecutively enrolled all adult patients with moderate to severe active IBD who had at least 2 years of follow-up after ustekinumab was initiated. LOR was defined as CDAI > 220 or HBI > 4 for Crohn’s disease (CD) and partial Mayo subscore > 3 for ulcerative colitis (UC) and with a modification in disease management. Results: Ninety patients were included (78 CD and 12 UC; mean age 37 years). Median levels of anti-ustekinumab antibodies (ATU) were significantly higher in patients with LOR compared to those with ongoing clinical response (15.2 µg/mL-eq CI (7.9–21.5) and 4.7 µg/mL-eq CI (2.1–10.5), respectively; p = 0.04). The area under the ROC curve (AUROC) for ATU in predicting LOR was 0.76. The optimal cut-off point for identifying patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80% and specificity of 85%. Uni- and multivariate analyses showed that serum ATU ≥ 9.5 µg/mL-eq (hazard ratio (HR) 2.54, 95%CI (1.80–5.93)), p = 0.022, prior vedolizumab (HR 2.78, 95%CI (1.09–3.34), p = 0.019) and prior azathioprine (HR 0.54, 95%CI (0.20–0.76), p = 0.014) exposures were the only factors independently associated with LOR to UST. Conclusion: In our real-life cohort, ATU was identified as an independent predictor of LOR to ustekinumab in patients with IBD. MDPI 2023-05-10 /pmc/articles/PMC10219534/ /pubmed/37240501 http://dx.doi.org/10.3390/jcm12103395 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roblin, Xavier
Duru, Gérard
Papamichael, Konstantinos
Cheifetz, Adam S.
Kwiatek, Sandy
Berger, Anne-Emmanuelle
Barrau, Mathilde
Waeckel, Louis
Nancey, Stephane
Paul, Stephane
Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title_full Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title_fullStr Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title_full_unstemmed Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title_short Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease
title_sort development of antibodies to ustekinumab is associated with loss of response in patients with inflammatory bowel disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219534/
https://www.ncbi.nlm.nih.gov/pubmed/37240501
http://dx.doi.org/10.3390/jcm12103395
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