Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn's Disease

The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. To investigate the association between inflammatory biochemical parameters and serum concen...

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Published in:Digestive diseases (Basel) Vol. 37; no. 2; p. 108
Main Authors: Beltrán, Belén, Iborra, Marisa, Sáez-González, Esteban, Marqués-Miñana, Maria R, Moret, Inés, Cerrillo, Elena, Tortosa, Luis, Bastida, Guillermo, Hinojosa, Joaquín, Poveda-Andrés, Jose Luis, Nos, Pilar
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Language:English
Published: Switzerland 2019
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Abstract The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn's disease (CD) patients. Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 μg/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 μg/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 μg/g, -respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 μg/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 μg/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman's rho correlation, 0.440; p < 0.05). IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD.
AbstractList The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn's disease (CD) patients. Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 μg/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 μg/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 μg/g, -respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 μg/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 μg/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman's rho correlation, 0.440; p < 0.05). IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD.
Author Poveda-Andrés, Jose Luis
Sáez-González, Esteban
Hinojosa, Joaquín
Nos, Pilar
Tortosa, Luis
Beltrán, Belén
Iborra, Marisa
Moret, Inés
Cerrillo, Elena
Marqués-Miñana, Maria R
Bastida, Guillermo
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  surname: Beltrán
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  surname: Sáez-González
  fullname: Sáez-González, Esteban
  email: Spainesteban.digestivo@gmail.com, Spainesteban.digestivo@gmail.com
  organization: Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spainesteban.digestivo@gmail.com
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  givenname: Maria R
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  organization: Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
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  surname: Bastida
  fullname: Bastida, Guillermo
  organization: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
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  surname: Hinojosa
  fullname: Hinojosa, Joaquín
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  surname: Poveda-Andrés
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– sequence: 11
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  surname: Nos
  fullname: Nos, Pilar
  organization: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
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Keywords Fecal calprotectin
Inflammatory bowel disease
Primary nonresponse
Trough levels
Infliximab
Crohn’s disease
Language English
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Snippet The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory...
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StartPage 108
SubjectTerms Adolescent
Adult
Aged
Crohn Disease - drug therapy
Crohn Disease - metabolism
Feces - chemistry
Female
Gastrointestinal Agents - therapeutic use
Humans
Infliximab - therapeutic use
Leukocyte L1 Antigen Complex - metabolism
Male
Middle Aged
Multivariate Analysis
Prospective Studies
Treatment Outcome
Young Adult
Title Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn's Disease
URI https://www.ncbi.nlm.nih.gov/pubmed/30149385
Volume 37
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