Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease.
OBJECTIVE
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.
Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
Waqqas
W
Afif
Edward V
EV
Loftus
William A
WA
Faubion
Sunanda V
SV
Kane
David H
DH
Bruining
Karen A
KA
Hanson
William J
WJ
Sandborn
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D000069285:Infliximab; D008297:Male; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab