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

Useful For

Trough level quantitation for evaluation of patients undergoing therapy with infliximab, infliximab-dyyb, infliximab-abda or infliximab-axxq

Profile Information

Test ID Reporting Name Available Separately Always Performed
INFX Infliximab, S No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
INXAB Infliximab Ab, S No No

Testing Algorithm

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

Reporting Name

Infliximab QN with Reflex to Ab, S

Specimen Type

Serum Red


Specimen Required


Patient Preparation:

1. Draw blood immediately before next scheduled dose (trough specimen).

2. For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Container/Tube: Red top (serum gel/SST are not acceptable)

Specimen Volume: 1 mL

Collection Instructions: Centrifuge within 2 hours of collection.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Frozen (preferred) 28 days
  Refrigerated  28 days

Clinical Information

Infliximab is a chimeric immunoglobulin (IgG1 kappa) targeting tumor necrosis factor-alpha (TNF-a), and it is currently US Food and Drug Administration (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.

 

The reference product for infliximab is Remicade (Janssen) and as of November 2021, four biosimilar products are FDA-approved: Renflexis, Inflectra, Ixifi and Avsola.

 

A biosimilar product is a biological product that it is highly similar to an FDA-approved biological product, known as the reference product, but manufactured by a different company. 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).

This assay has been verified to measure antibodies to infliximab (Remicade, Janssen Pharmaceuticals), and the biosimilars infliximab-dyyb (Inflectra, Pfizer Inc), infliximab-abda (Renflexis, Organon), and infliximab-axxq (Avsola, Amgen) with no analytical differences between the detection of ATI for the four drugs. Inflectra, Renflexis, and Avsola have the same primary amino acid sequence. Therefore, "infliximab" will be used to refer to both the reference product and the biosimilar products interchangeably. This test cannot distinguish between Remicade and the infliximab biosimilar products.

 

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) Male patients seem to clear infliximab faster than female patients.(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 reach steady state and stabilize after 14 weeks (approximately 100 days). Quantitation of peak infliximab concentrations is strongly discouraged.

Reference Values

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 ≥50 U/mL

Interpretation

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 treatment with a different pharmaceutical agent.

 

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

Clinical Reference

1. Colombel JF, Sandborn WJ, Reinisch W, et al: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr;362(15):1383-1395. doi: 10.1056/NEJMoa0904492

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 May;9(5):421-427.e1. doi: 10.1016/j.cgh.2011.02.008

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 Apr;91(4):635-646. doi: 10.1038/clpt.2011.328

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 May;105(5):1133-1139. doi: 10.1038/ajg.2010.9

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. doi: 10.1007/s00535-013-0829-7

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 Mar;46(3):310-318. doi: 10.3109/00365521.2010.536254

7. Feuerstein JD, Nguyen GC, Kupfer SS, et al: American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017 Sep;153(3):827-834. doi: 10.1053/j.gastro.2017.07.032

8. 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. doi: 10.1097/MIB.0000000000000855

Report Available

3 to 6 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

80230

82397-(if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
INFXR Infliximab QN with Reflex to Ab, S 39803-2

 

Result ID Test Result Name Result LOINC Value
63000 Infliximab, S 39803-2
36847 Interpretation 59462-2

Method Name

INFXR, INFX: Selective Reaction Monitoring Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

INXAB: Electrochemiluminescent Bridging Immunoassay with Acid Dissociation

Forms

If not ordering electronically, complete, print, and send 1 of the following with specimen:

-Gastroenterology and Hepatology Client Test Request (T728)

-Therapeutics Test Request (T831)

Day(s) Performed

INFX: Monday, Wednesday, Thursday

INXAB: Monday, Wednesday, Friday