Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease

Objective: Deep remission defined by clinical-biomarker remission and mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimal cut- off concentration for infliximab and adalimumab during maintenance therapy associated with...

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Autores: Pascual-Marmaneu, O, Belles-Medall, MD, Ferrando-Piqueres, R, Almela-Notari, P, Mendoza-Aguilera, M, Alvarez-Martin, T
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p13679
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/13679
Access Level:acceso abierto
Palabra clave:Infliximab
Adalimumab
Inflammatory bowel diseases
Crohn disease
Colitis ulcerative
Therapeutic drug monitoring
Phormacokinetics
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spelling Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel diseasePascual-Marmaneu, OBelles-Medall, MDFerrando-Piqueres, RAlmela-Notari, PMendoza-Aguilera, MAlvarez-Martin, TInfliximabAdalimumabInflammatory bowel diseasesCrohn diseaseColitis ulcerativeTherapeutic drug monitoringPhormacokineticsObjective: Deep remission defined by clinical-biomarker remission and mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimal cut- off concentration for infliximab and adalimumab during maintenance therapy associated with deep remission. The secondary objective, was to evaluate the influence of variables on anti tumor necrosis factor-alpha concentrations and deep remission. Method: Retrospective study including 120 and 122 patients inflammatory bowel disease diagnosed who received maintenance therapy with infliximab and adalimumab. Biomarker remission was considered by C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Crohn's disease clinical remission was defined by a Harvey Bradshaw score < 5 and mucosal healing by a simple endoscopic score for Crohn's disease< 3. In ulcerative colitis, it was defined as a Mayo total score < 3 and Mayo endoscopic subscore < 2. Receiver operating characteristic test was performed to determine drug concentration thresholds associated with deep remission. Anti tumor necrosis factor- alpha concentrations were classified into quartiles. X-2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics andserological facto C-reactive protein rs associated with deep remission. Results: Anti tumor necrosis factor-alpha concentrations were higher inpatients with deep remission, in infliximab (4.4, interquartile range: 3.3-6.5 vs 2.3, interquartile range: 1.1-4.2 mu g/mL, P < 0.005) and adalimumab (6.3, interquartile range: 4.2-8.2 vs 3.9, interquartile range: 2.4-5.5 mu g/mL,P < 0.005). A Receiver operating characteristic test identified a concentration threshold of 3.1 mu g/mL in infliximab (area under the Receiver operating characteristic test curve, 0.72) and 6.3 mu g/mL in adalimumab (area underreceiver operating characteristic test curve, 0.75) associated with deep remission. Factors associated with the highest quartiles of serum infliximab concentration were: elevated body mass index, absence of previous inflammatory bowel disease-surgery, C-reactive protein < 5 mg/L, and fecal calprotectin < 100 mu g/g. In adalimumab, higher quartiles were related to concomitant immunosuppressants, low body mass index, absence of previous inflammatory bowel disease-surgery, and C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Multivariate regression identified fecal calprotectin < 100 mu g/g, C-reactive protein < 5 mg/L, infliximab >= 3.1 mu g/mL and adalimumab concentrations >= 6.3 mu g/mL as factors significantly associated with deep remission. Conclusions: Trough infliximab and adalimumab concentrations, C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g are associated with deep remission during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for inflixi-mab and adalimumab respectively, were identified as deep remission predictors.ELSEVIER SCIENCE INC2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/13679FARMACIA HOSPITALARIAISSN: 11306343ISSNe: 21718695reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p136792026-06-11T12:45:17Z
dc.title.none.fl_str_mv Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
title Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
spellingShingle Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
Pascual-Marmaneu, O
Infliximab
Adalimumab
Inflammatory bowel diseases
Crohn disease
Colitis ulcerative
Therapeutic drug monitoring
Phormacokinetics
title_short Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
title_full Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
title_fullStr Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
title_full_unstemmed Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
title_sort Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease
dc.creator.none.fl_str_mv Pascual-Marmaneu, O
Belles-Medall, MD
Ferrando-Piqueres, R
Almela-Notari, P
Mendoza-Aguilera, M
Alvarez-Martin, T
author Pascual-Marmaneu, O
author_facet Pascual-Marmaneu, O
Belles-Medall, MD
Ferrando-Piqueres, R
Almela-Notari, P
Mendoza-Aguilera, M
Alvarez-Martin, T
author_role author
author2 Belles-Medall, MD
Ferrando-Piqueres, R
Almela-Notari, P
Mendoza-Aguilera, M
Alvarez-Martin, T
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Infliximab
Adalimumab
Inflammatory bowel diseases
Crohn disease
Colitis ulcerative
Therapeutic drug monitoring
Phormacokinetics
topic Infliximab
Adalimumab
Inflammatory bowel diseases
Crohn disease
Colitis ulcerative
Therapeutic drug monitoring
Phormacokinetics
description Objective: Deep remission defined by clinical-biomarker remission and mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimal cut- off concentration for infliximab and adalimumab during maintenance therapy associated with deep remission. The secondary objective, was to evaluate the influence of variables on anti tumor necrosis factor-alpha concentrations and deep remission. Method: Retrospective study including 120 and 122 patients inflammatory bowel disease diagnosed who received maintenance therapy with infliximab and adalimumab. Biomarker remission was considered by C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Crohn's disease clinical remission was defined by a Harvey Bradshaw score < 5 and mucosal healing by a simple endoscopic score for Crohn's disease< 3. In ulcerative colitis, it was defined as a Mayo total score < 3 and Mayo endoscopic subscore < 2. Receiver operating characteristic test was performed to determine drug concentration thresholds associated with deep remission. Anti tumor necrosis factor- alpha concentrations were classified into quartiles. X-2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics andserological facto C-reactive protein rs associated with deep remission. Results: Anti tumor necrosis factor-alpha concentrations were higher inpatients with deep remission, in infliximab (4.4, interquartile range: 3.3-6.5 vs 2.3, interquartile range: 1.1-4.2 mu g/mL, P < 0.005) and adalimumab (6.3, interquartile range: 4.2-8.2 vs 3.9, interquartile range: 2.4-5.5 mu g/mL,P < 0.005). A Receiver operating characteristic test identified a concentration threshold of 3.1 mu g/mL in infliximab (area under the Receiver operating characteristic test curve, 0.72) and 6.3 mu g/mL in adalimumab (area underreceiver operating characteristic test curve, 0.75) associated with deep remission. Factors associated with the highest quartiles of serum infliximab concentration were: elevated body mass index, absence of previous inflammatory bowel disease-surgery, C-reactive protein < 5 mg/L, and fecal calprotectin < 100 mu g/g. In adalimumab, higher quartiles were related to concomitant immunosuppressants, low body mass index, absence of previous inflammatory bowel disease-surgery, and C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g. Multivariate regression identified fecal calprotectin < 100 mu g/g, C-reactive protein < 5 mg/L, infliximab >= 3.1 mu g/mL and adalimumab concentrations >= 6.3 mu g/mL as factors significantly associated with deep remission. Conclusions: Trough infliximab and adalimumab concentrations, C-reactive protein < 5 mg/L and fecal calprotectin < 100 mu g/g are associated with deep remission during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for inflixi-mab and adalimumab respectively, were identified as deep remission predictors.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/13679
url https://fisabio.portalinvestigacion.com/publicaciones/13679
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER SCIENCE INC
publisher.none.fl_str_mv ELSEVIER SCIENCE INC
dc.source.none.fl_str_mv FARMACIA HOSPITALARIA
ISSN: 11306343
ISSNe: 21718695
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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