Serum trough infliximab and anti-infliximab antibodies in a cohort of gastroenterology and rheumatology patients' infliximab therapeutic drug monitoring.
BACKGROUND
Infliximab, a monoclonal antibody directed against tumour necrosis factor, is widely used in the treatment of chronic inflammatory conditions including Crohn's disease and rheumatoid arthritis. Its use is limited by development of anti-infliximab antibodies, which can lead to loss of therapeutic efficacy. Serum infliximab and anti-infliximab antibody measurements have recently become routinely available in the UK. The study aimed to assess the clinical utility of antibodies as an adjunct to trough infliximab.


METHODS
Serum trough infliximab was measured in 201 samples from 108 gastroenterology and rheumatology patients on maintenance infliximab therapy. Results were correlated with C-reactive protein concentrations. Total anti-infliximab antibodies were measured in 164 samples.


RESULTS
The median (25th-75th percentile) trough infliximab was 3.7 µg/mL (1.2-5.2 µg/mL) and 23% of samples had a concentration ≤1 µg/mL. A notable proportion had positive anti-infliximab antibodies: 84/164 (51%), which subdivided to 85% and 28% with infliximab ≤1 and >1 µg/mL, respectively.Serum C-reactive protein was found to be significantly higher where infliximab was ≤1 compared to >1 µg/mL (10 mg/L [<5-24 mg/L] vs. <5 mg/L [<5-8 mg/L], P < 0.01), although a strict correlation was not observed. The relationship between trough infliximab and C-reactive protein differed depending on antibody status and there was no association between C-reactive protein and the presence or absence of antibodies.


CONCLUSIONS
Our findings support measurement of anti-infliximab antibodies only in the context of low infliximab concentrations <1 µg/mL. A higher therapeutic cut-off may be relevant in patients with negative antibodies. Further work is indicated to investigate the clinical significance of positive antibodies with therapeutic infliximab concentrations.
Department of Clinical Biochemistry, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands, UK nicola.barlow1@nhs.net.
Nicola L
NL
Barlow
Department of Clinical Biochemistry, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands, UK.
Pervaz
P
Mohammed
Department of Clinical Biochemistry, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands, UK.
Jonathan D
JD
Berg
D000906:Antibodies / Q000097:blood*; D018501:Antirheumatic Agents / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D016903:Drug Monitoring; D005260:Female; D005765:Gastrointestinal Agents / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy; D000069285:Infliximab / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male
D000906:Antibodies; D018501:Antirheumatic Agents; D005765:Gastrointestinal Agents; D000069285:Infliximab
Drugs; analytes; clinical studies; gastrointestinal disorders