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Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease

BACKGROUND: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic dr...

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Autores principales: Carlsen, Arne, Omdal, Roald, Leitao, Kristian Øgreid, Isaksen, Kjetil, Hetta, Anne Kristine, Karlsen, Lars Normann, Aabakken, Lars, Bolstad, Nils, Warren, David, Lundin, Knut E.A., Grimstad, Tore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881967/
https://www.ncbi.nlm.nih.gov/pubmed/29623105
http://dx.doi.org/10.1177/1756284818759930
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author Carlsen, Arne
Omdal, Roald
Leitao, Kristian Øgreid
Isaksen, Kjetil
Hetta, Anne Kristine
Karlsen, Lars Normann
Aabakken, Lars
Bolstad, Nils
Warren, David
Lundin, Knut E.A.
Grimstad, Tore
author_facet Carlsen, Arne
Omdal, Roald
Leitao, Kristian Øgreid
Isaksen, Kjetil
Hetta, Anne Kristine
Karlsen, Lars Normann
Aabakken, Lars
Bolstad, Nils
Warren, David
Lundin, Knut E.A.
Grimstad, Tore
author_sort Carlsen, Arne
collection PubMed
description BACKGROUND: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic drug concentrations were associated with increased levels of disease activity. METHODS: In a single-center cross-sectional study, we included patients with ulcerative colitis or Crohn’s disease who were receiving infliximab or adalimumab maintenance therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal calprotectin], antidrug antibodies and serum drug concentrations were recorded. Therapeutic drug concentrations were defined as 3–8 mg/liter for infliximab and 5–12 mg/liter for adalimumab. RESULTS: Of 210 patients included, 137 (65.2%) had Crohn’s disease. In the adalimumab group, subtherapeutic drug concentrations were measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients with Crohn’s disease. In the infliximab group, subtherapeutic drug concentrations were found in 23% (ulcerative colitis) and 30.3% (Crohn’s disease) of patients. In Crohn’s disease, subtherapeutic adalimumab concentrations were associated with higher fecal calprotectin and CRP concentrations compared with therapeutic concentrations. Subtherapeutic infliximab concentrations in patients with Crohn’s disease were also associated with higher CRP concentrations compared with therapeutic concentrations. CONCLUSIONS: The prevalence of subtherapeutic drug levels ranged from 17% to 30%. In patients with Crohn’s disease, subtherapeutic serum drug concentrations were associated with significantly higher disease activity with both anti-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054]
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spelling pubmed-58819672018-04-05 Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease Carlsen, Arne Omdal, Roald Leitao, Kristian Øgreid Isaksen, Kjetil Hetta, Anne Kristine Karlsen, Lars Normann Aabakken, Lars Bolstad, Nils Warren, David Lundin, Knut E.A. Grimstad, Tore Therap Adv Gastroenterol Original Research BACKGROUND: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic drug concentrations were associated with increased levels of disease activity. METHODS: In a single-center cross-sectional study, we included patients with ulcerative colitis or Crohn’s disease who were receiving infliximab or adalimumab maintenance therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal calprotectin], antidrug antibodies and serum drug concentrations were recorded. Therapeutic drug concentrations were defined as 3–8 mg/liter for infliximab and 5–12 mg/liter for adalimumab. RESULTS: Of 210 patients included, 137 (65.2%) had Crohn’s disease. In the adalimumab group, subtherapeutic drug concentrations were measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients with Crohn’s disease. In the infliximab group, subtherapeutic drug concentrations were found in 23% (ulcerative colitis) and 30.3% (Crohn’s disease) of patients. In Crohn’s disease, subtherapeutic adalimumab concentrations were associated with higher fecal calprotectin and CRP concentrations compared with therapeutic concentrations. Subtherapeutic infliximab concentrations in patients with Crohn’s disease were also associated with higher CRP concentrations compared with therapeutic concentrations. CONCLUSIONS: The prevalence of subtherapeutic drug levels ranged from 17% to 30%. In patients with Crohn’s disease, subtherapeutic serum drug concentrations were associated with significantly higher disease activity with both anti-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054] SAGE Publications 2018-03-14 /pmc/articles/PMC5881967/ /pubmed/29623105 http://dx.doi.org/10.1177/1756284818759930 Text en © The Author(s), 2018 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Carlsen, Arne
Omdal, Roald
Leitao, Kristian Øgreid
Isaksen, Kjetil
Hetta, Anne Kristine
Karlsen, Lars Normann
Aabakken, Lars
Bolstad, Nils
Warren, David
Lundin, Knut E.A.
Grimstad, Tore
Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title_full Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title_fullStr Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title_full_unstemmed Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title_short Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease
title_sort subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in crohn’s disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881967/
https://www.ncbi.nlm.nih.gov/pubmed/29623105
http://dx.doi.org/10.1177/1756284818759930
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