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

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.

Conflict of interest statement

CONFLICT OF INTEREST

Guarantor of the article: Waqqas Afif, MD.

Potential competing interests: William Sandborn is a consultant to and has received research support from Centocor, Schering-Plough, Abbott Laboratories, and UCB Pharma. Edward Loft us has received research support from Schering-Plough and has participated in continuing medical education activities sponsored in part by Centocor. William Faubion is a consultant to and has received research support from Centocor and Abbot Laboratories. Dr Kane is a consultant to Abbott Laboratories.

Figures

Figure 1.

Treatment algorithm in patients with clinical symptoms (infliximab and HACA concentrations). 1Patients should save endoscopic or radiologic imaging. 2This strategy may be preferable. HACA, human anti-chimeric antibody; TNF, tumor necrosis factor.