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Test Catalog

Test ID: INFXR    
Infliximab Quantitation with Reflex to Antibodies to Infliximab, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Trough level quantitation for evaluation of patients with loss of response to infliximab and infliximab-dyyb

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Infliximab will be performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on all samples. When Infliximab results are below 5.1 mcg/mL, testing for antibodies to infliximab will be performed at an additional charge.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Infliximab (Remicade, Renflexis, Inflectra) is a chimeric immunoglobulin (IgG1 kappa) targeting tumor necrosis factor-alpha (TNF-a), and it is currently FDA-approved for the treatment of multiple inflammatory conditions. Infliximab binds to soluble TNF-a and transmembrane homotrimers, which are found on the surface of macrophages and T-cells, with similar affinity. Infliximab has the ability to mediate complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, which leads to the lysis of target cells.

 

Infliximab pharmacokinetic properties may vary with disease and clearance is affected by concomitant use of immunosuppressants, high concentrations of TNF-a and C-reactive proteins,(1,2) low albumin concentrations, high body mass index, and presence of antibodies to infliximab (ATI), also known as human antichimeric antibodies (HACA).(3) Males seem to clear infliximab faster than females.(3)

 

Several studies have demonstrated that infliximab quantitation in the setting of loss of response to therapy can aid in patient management, as trough concentrations defined as therapeutic have been associated with superior clinical response and improved prognosis.(4-6)

 

Evaluation of infliximab concentrations may be of value for all inflammatory diseases for which it is prescribed. Primary indications for testing of infliximab include loss of response, partial response on initiation of therapy, autoimmune or hypersensitivity reactions, primary nonresponse, reintroduction after drug holiday, endoscopic/computed tomography enterography recurrence (in inflammatory bowel disease), and acute infusion reactions.

 

Measurement of infliximab concentrations is indicated at trough, immediately prior to the next scheduled infusion. Low trough concentrations may be correlated with loss of response to infliximab. Assessment of antibodies to infliximab is suggested when infliximab quantitation at trough is 5.0 mcg/mL or less. Infliximab concentrations tend to stabilize after 14 weeks (approximately 100 days). Quantitation of peak infliximab concentrations is strongly discouraged.

 

The ATI assay has been verified to analyze infliximab and infliximab-dyyb (Inflectra, Pfizer Inc) with no analytical differences between the 2 drugs quantitation. Inflectra has the same primary amino acid sequence as Remicade and Renflexis. Therefore, "infliximab" will be used to refer to both the reference product and the biosimilar product interchangeably.

 

A biosimilar product is a biological product that is approved based on showing that it is highly similar to an FDA-approved biological product, known as the reference product. No clinically meaningful differences in terms of safety and effectiveness from the reference product are present. Only minor differences in clinically inactive components are allowable in biosimilar products. In contrast to generic medications, a prescription of biosimilars needs to come from the ordering physician and not the dispensing pharmacy (pharmacies cannot substitute a biosimilar for another medication; a separate prescription is required).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

INFLIXIMAB QUANTITATION:

Limit of quantitation is 1.0 mcg/mL. Therapeutic ranges are disease specific.

 

Pediatric reference ranges are not established.

 

INFLIXIMAB ANTIBODIES

Absence of antibodies to infliximab (ATI) is defined as <50 U/mL

Presence of ATI is reported as positive when concentrations are > or =50 U/mL

Interpretation Provides information to assist in interpretation of the test results

Low trough concentrations may be correlated with loss of response to infliximab. For infliximab trough concentrations 5.0 mcg/mL or less, testing for antibodies to infliximab (ATI) is suggested.

 

For infliximab trough concentrations above 5.0 mcg/mL, the presence of ATI is unlikely; patients experiencing loss of response to infliximab may benefit from an increased dose or a shorter infusion interval.

 

Results above 35 mcg/mL are suggestive of a blood draw at a time-point in treatment other than trough.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Toxicity effects other than acute hypersensitivity infusion reactions have not been described nor correlated with infliximab concentrations.

 

During the initial induction phase of treatment (weeks 0, 2, and 6), steady-state has not been achieved and concentrations of infliximab may vary significantly between infusions.(3)

 

Therapeutic concentrations of infliximab may vary according to the disease (eg, Crohn disease versus ulcerative colitis versus rheumatoid arthritis).

 

Samples containing more than 12.5 ng/mL biotin (vitamin B7) may interfere (in the form of depressed signal) with INXAB / Infliximab Antibodies, Serum.

 

For antibodies-to-infliximab (ATI), pediatric and adult reference ranges were validated, and the presence of an ATI is established as greater than or equal to 50 U/mL by our bridging electrochemiluminescent/acid dissociation method.

 

The presence of endogenous infliximab is a recognized interference in most ATI methods. This assay includes an acid dissociation step, which partially mitigates this interference. Tolerance up to 12.5 mcg/mL infliximab has been documented, although this is also determined by the titer of the ATI present in the patient sample.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Colombel JF, Sandborn WJ, Reinisch W, et al: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362:1383-1395

2. Jurgens M, Mahachie John JM, Cleynen I, et al: Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2011;9:421-427.e1

3. Ordas I, Mould DR, Feagan BG, Sandborn WJ: Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012;91:635-646

4. Afif W, Loftus EV Jr, Faubion WA, et al: Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105:1133-1139

5. Imaeda H, Bamba S, Takahashi K, et al: Relationship between serum infliximab trough levels and endoscopic activities in patients with Crohn's disease under scheduled maintenance treatment. J Gastroenterol. 2014 Apr;49(4):674-682

6. Steenholdt C, Bendtzen K, Brynskov J, et al: Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease. Scand J Gastroenterol. 2011;46:310-318

7. Silva-Ferreira F, Afonso J, Pinto-Lopes P, Magro F: A systematic review on Infliximab and Adalimumab drug monitoring: Levels, clinical outcomes and assays. Inflamm Bowel Dis. 2016 Sep;22(9):2289-2301