Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab

Konstantinos Papamichael, Karen A. Chachu, Ravy K. Vajravelu, Byron P Vaughn, Josephine Ni, Mark T. Osterman, Adam S. Cheifetz

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background & Aims Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. Methods We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. Results Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09–0.27; P <.001), IBD-related surgery (HR, 0.30; 95% CI, 0.11–0.80; P =.017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07–0.33; P <.001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07–0.84; P =.025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04–0.78; P =.023). Conclusions In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

Original languageEnglish (US)
Pages (from-to)1580-1588.e3
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Inflammatory Bowel Diseases
Drug Monitoring
Serum
Confidence Intervals
Treatment Failure
Hospitalization
Antibodies
Pharmaceutical Preparations
Infliximab
Crohn Disease
Multicenter Studies
Retrospective Studies
Tumor Necrosis Factor-alpha
Regression Analysis
Therapeutics

Keywords

  • CD
  • Immunogenicity
  • Monitoring Therapy
  • Ulcerative Colitis

Cite this

Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab. / Papamichael, Konstantinos; Chachu, Karen A.; Vajravelu, Ravy K.; Vaughn, Byron P; Ni, Josephine; Osterman, Mark T.; Cheifetz, Adam S.

In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 10, 01.10.2017, p. 1580-1588.e3.

Research output: Contribution to journalArticle

Papamichael, Konstantinos ; Chachu, Karen A. ; Vajravelu, Ravy K. ; Vaughn, Byron P ; Ni, Josephine ; Osterman, Mark T. ; Cheifetz, Adam S. / Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab. In: Clinical Gastroenterology and Hepatology. 2017 ; Vol. 15, No. 10. pp. 1580-1588.e3.
@article{16361a7625c343a29a43d5b3e4187a09,
title = "Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab",
abstract = "Background & Aims Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. Methods We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. Results Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95{\%} confidence interval [CI], 0.09–0.27; P <.001), IBD-related surgery (HR, 0.30; 95{\%} CI, 0.11–0.80; P =.017), IBD-related hospitalization (HR, 0.16; 95{\%} CI, 0.07–0.33; P <.001), antibodies to infliximab (HR, 0.25; 95{\%} CI, 0.07–0.84; P =.025), and serious infusion reaction (HR, 0.17; 95{\%} CI, 0.04–0.78; P =.023). Conclusions In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.",
keywords = "CD, Immunogenicity, Monitoring Therapy, Ulcerative Colitis",
author = "Konstantinos Papamichael and Chachu, {Karen A.} and Vajravelu, {Ravy K.} and Vaughn, {Byron P} and Josephine Ni and Osterman, {Mark T.} and Cheifetz, {Adam S.}",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/j.cgh.2017.03.031",
language = "English (US)",
volume = "15",
pages = "1580--1588.e3",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "10",

}

TY - JOUR

T1 - Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab

AU - Papamichael, Konstantinos

AU - Chachu, Karen A.

AU - Vajravelu, Ravy K.

AU - Vaughn, Byron P

AU - Ni, Josephine

AU - Osterman, Mark T.

AU - Cheifetz, Adam S.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background & Aims Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. Methods We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. Results Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09–0.27; P <.001), IBD-related surgery (HR, 0.30; 95% CI, 0.11–0.80; P =.017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07–0.33; P <.001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07–0.84; P =.025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04–0.78; P =.023). Conclusions In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

AB - Background & Aims Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. Methods We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. Results Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09–0.27; P <.001), IBD-related surgery (HR, 0.30; 95% CI, 0.11–0.80; P =.017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07–0.33; P <.001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07–0.84; P =.025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04–0.78; P =.023). Conclusions In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

KW - CD

KW - Immunogenicity

KW - Monitoring Therapy

KW - Ulcerative Colitis

UR - http://www.scopus.com/inward/record.url?scp=85024862765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024862765&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2017.03.031

DO - 10.1016/j.cgh.2017.03.031

M3 - Article

VL - 15

SP - 1580-1588.e3

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 10

ER -