Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease

Waqqas Afif, Edward Vincent Loftus, Jr, William Alvis Faubion, Sunanda V. Kane, David H. Bruining, Karen A. Hanson, William J. Sandborn

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Abstract

OBJECTIVES: Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations.METHODS: The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management.RESULTS: One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49%), partial response after initiation of infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted treatment decisions in 73%. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92% of patients, whereas dose escalation had a response of 17%. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86% of patients whereas changing to another anti-TNF agent had a response of 33%. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76% of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62% of the time.CONCLUSIONS: Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.

Original languageEnglish (US)
Pages (from-to)1133-1139
Number of pages7
JournalAmerican Journal of Gastroenterology
Volume105
Issue number5
DOIs
StatePublished - May 2010

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Inflammatory Bowel Diseases
Anti-Idiotypic Antibodies
Tumor Necrosis Factor-alpha
Infliximab
Delayed Hypersensitivity
Medical Records
Therapeutics
Inflammation

ASJC Scopus subject areas

  • Gastroenterology

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Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. / Afif, Waqqas; Loftus, Jr, Edward Vincent; Faubion, William Alvis; Kane, Sunanda V.; Bruining, David H.; Hanson, Karen A.; Sandborn, William J.

In: American Journal of Gastroenterology, Vol. 105, No. 5, 05.2010, p. 1133-1139.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVES: Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations.METHODS: The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management.RESULTS: One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49{\%}), partial response after initiation of infliximab (22{\%}), and possible autoimmune/delayed hypersensitivity reaction (10{\%}). HACAs were identified in 35 patients (23{\%}) and therapeutic infliximab concentrations in 51 patients (33{\%}). Of 177 tests assessed, the results impacted treatment decisions in 73{\%}. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92{\%} of patients, whereas dose escalation had a response of 17{\%}. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86{\%} of patients whereas changing to another anti-TNF agent had a response of 33{\%}. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76{\%} of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62{\%} of the time.CONCLUSIONS: Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.",
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AU - Kane, Sunanda V.

AU - Bruining, David H.

AU - Hanson, Karen A.

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N2 - OBJECTIVES: Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations.METHODS: The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management.RESULTS: One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49%), partial response after initiation of infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted treatment decisions in 73%. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92% of patients, whereas dose escalation had a response of 17%. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86% of patients whereas changing to another anti-TNF agent had a response of 33%. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76% of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62% of the time.CONCLUSIONS: Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.

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