Infliximab Activity & Neutralizing Antibody
This test is used to aid in the evaluation of response failure to infliximab (Remicade). Serum levels of infliximab and anti-infliximab antibodies are reported based on the bioactivity of the drug, i.e. its ability to inhibit tumor necrosis factor alpha (TNF-α). The test uses the principles of iLite™ technology (see details under "How it works"). At this time, this is the only clinical assay available for detecting biologically active infliximab in serum.
Infliximab is used for the treatment of patients with chronic inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and psoriasis. Unfortunately, many patients receiving the recommended dose have inadequate responses, or experience secondary response failure. This necessitates intensified therapy or change to alternative treatments. Rise of anti-infliximab antibodies is seen in about 40–50% of patients treated with this drug. Recent studies on Crohn’s patients showed that the strategy using test results for infliximab and anti-infliximab antibodies is more cost effective than empiric dose escalation for managing patients who lost responsiveness to infliximab.
- Spotlight on Testing Video: Test-Guided Management of Treatment Failure to
TNF-alpha antagonists by Julio Delgado, MD, MS
Features and Benefits
- Aids in rational therapeutic decision for patients on TNF-blocking therapy
- Test measures bioactivity using reporter cells
- Recommended CPT code 86352 x 2
- Interfaced reports
How it works
- TNF-α activity and its inhibition by infliximab are measured by stimulation of cells carrying a TNF-responding luciferase gene, and quantifying luciferase expression by luminometry. The assay uses the principles of iLite™ technology (reference).
- View the method brochure (download)
- The following cutoff values are used: 0.65 ug/mL (for infliximab), and 1:20 dilution (for anti-infliximab antibody). Values below these cutoffs will be reported as "Not Detected".
How it compares with other tests
Methods to monitor anti-drug antibody (ADA) levels in serumThe main difference is that ARUP's test measures bioactivity of the drug and of the neutralizing antibody.
|ARUP Infliximab assay
(reporter gene assay)
|Fluid-phase RIA||Homogeneous mobility-shift assay (size exclusion HPLC)|
|What the test measures
|in vivo relevance to the drug's capacity to inhibit TNF in patient||High||Low||Moderate||Moderate|
|Specifically detects ADAs with drug-neutralizing function||
|Detection of IgG4 antibodies (major isotype of ADAs)||Yes||No||Yes||Yes|
|Possibility of false negative ADA due to drug in sample||Low||High||Low||Low|
|Possibility of false positives due to neoepitopes, nonspecific binding, rheumatoid factors, complement components||Low||High||Low||Low|
- Steenholdt C et al. (2013) Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2013 Jul 22. [Epub ahead of print].
- Velayos FS et al, (2013) A test-based strategy is more cost effective than empiric dose escalation for patients with Crohn's disease who lose responsiveness to infliximab. Clin Gastroenterol Hepatol. 11(6):654-66. doi: 10.1016/j.cgh.2012.12.035.
- Bendtzen K (2013) Personalized Medicine: Theranostics (Therapeutics Diagnostics) Essential for Rational Use of Tumor Necrosis Factor-alpha Antagonists. Discov Med, 15(83):201-211
- Lallemand C et al, (2011) Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFalpha antagonists. J Immunol Meth. 373: 229-239. doi: 10.1016/j.jim.2011.08.022.
- Bendtzen, K. (2011) Is there a need for immunopharmacologic guidance of anti–tumor necrosis factor therapies?. Arthritis & Rheumatism, 63: 867–870. doi: 10.1002/art.30207
- Radstake TR et al, (2009) Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis.. Ann Rheum Dis. 11:1739-45. doi: 10.1136/ard.2008.092833
Test Report Examples
|Test Name||Infliximab Activity and Neutralizing Antibody|
|Method||Cell culture / Stimulated cell function assay / Chemiluminescent immunoassay, quantitative and semi-quantitative|
|Specimen required||1 mL serum, collect before infliximab infusion|