Test Catalog

Test Id : ADALX

Adalimumab Quantitative with Reflex to Antibody, Serum

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

Highlights

Adalimumab (brand name Humira) is a fully human therapeutic monoclonal antibody targeting tumor necrosis factor alpha, a proinflammatory cytokine that is upregulated in several autoimmune inflammatory states.

 

Adalimumab is FDA-approved for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis; ankylosing spondylitis, pediatric and adult Crohn disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa and uveitis. Adalimumab is a subcutaneous injection, usually self-administered every other week at a fixed dose of 40 mg in adults, although dosing can vary.

 

Testing for adalimumab concentration and presence of anti-adalimumab antibodies is helpful to adjust therapeutic strategies for patients starting therapy (proactive monitoring), and to adjust dosing or treatment strategy when partial response or loss of response to therapy is observed, manifested as recurrence of symptoms.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
ADLAB Adalimumab Ab, S No No

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

If the result is 8.0 mcg/mL or less, then adalimumab antibody test will be performed at an additional charge.

Method Name
A short description of the method used to perform the test

Enzyme-Linked Immunosorbent Assay (ELISA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Adalimumab QN with Reflex to Ab, S

Aliases
Lists additional common names for a test, as an aid in searching

Humira

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

If the result is 8.0 mcg/mL or less, then adalimumab antibody test will be performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: For 12 hours before specimen collection, it is recommended that the patient not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Forms

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

-Gastroenterology and Hepatology Client Test Request (T728)

-Therapeutics Test Request (T831)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.35 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

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

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

If the result is 8.0 mcg/mL or less, then adalimumab antibody test will be performed at an additional charge.

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

Adalimumab, sold under the brand name Humira, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, chronic psoriasis, amongst others. Adalimumab is a tumor necrosis factor (TNF)-inhibiting, antiinflammatory, biologic medication. It binds to TNF-alpha, which normally binds to TNF-alpha receptors, leading to the inflammatory response of autoimmune diseases. By binding to TNF-alpha, adalimumab reduces inflammatory response. Because TNF-alpha is also part of the immune system that protects the body from infection, treatment with adalimumab may increase the risk of infections. Treatment with adalimumab is effective in reducing disease activity, offers significant benefits in quality of life, and may have the potential to change the progression of the disease when given early. However, over 30% of patients fail to respond to anti-TNF-alpha therapy, and approximately 60% of patients who responded initially lose the response over time and require either drug dose-escalation or switch to an alternative therapy in order to maintain response.(1)

 

Reasons for primary loss of response are not well understood but may include disease processes mediated by proinflammatory molecules other than TNF. Secondary loss of response, on the other hand, is associated with low serum albumin, high body-mass index, the degree of systemic inflammation and development of an immune response to therapy, or immunogenicity.(2,3) Antidrug antibody formation may increase drug clearance in treated patients or neutralize the drug effect, thereby potentially contributing to the loss of response. Antidrug antibodies could also cause adverse events such as serum sickness and hypersensitivity reactions.(4) Currently, adalimumab quantitation is commonly performed in conjunction with immunogenicity assessment for antibodies to adalimumab (ATA). Most often, this testing is ordered in patients on therapy who are experiencing partial or complete loss of response.

 

TNF inhibitor therapies are expensive and adverse events include greater risk for infections, such as reactivation of latent tuberculosis or hepatitis B, infusion or injection site reactions, cutaneous reactions, and reports of hepatoxicity, demyelinating disease, and higher incidence of mortality and hospitalization in heart failure patients have been documented.

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.

ADALIMUMAB QUANTITATIVE

Limit of quantitation is 0.8 mcg/mL. Optimal therapeutic ranges are disease specific.

ADALIMUMAB ANTIBODY

<14.0 AU/mL

Interpretation
Provides information to assist in interpretation of the test results

Currently, adalimumab quantitation is one of the most commonly tested monoclonal antibodies in routine clinical practice; this testing is generally performed in conjunction with immunogenicity assessment for antibodies to adalimumab (ATA). Most often, this testing is ordered for patients with inflammatory bowel disease (IBD) who are on adalimumab therapy and who are experiencing loss of response (reactive monitoring),(5) but the testing may be ordered for anyone on adalimumab-even when treatment is going well (proactive monitoring).(6-8)

 

Results from adalimumab and ATA testing play an important role in patient management. In the setting of loss of response to adalimumab therapy, for adults with active inflammatory bowel disease (IBD), a clinical decision tool from the American Gastroenterology Association(9,10) suggests the following scenarios for a blood draw that occurred at trough, immediately before the next injection dose:

For patients who have undetectable or low concentrations of adalimumab (<8 mcg/mL) but no detectable ATA, the patient care team may choose to increase the dose of adalimumab in an attempt to increase the amount of the drug in circulation.

 

If the patient has subtherapeutic adalimumab concentrations (<8 mcg/mL) in the presence of an ATA, in many cases, the patient care team may switch the patient to another TNF inhibitor.

 

For patients with increased trough concentrations of adalimumab (therapeutic or greater), whether an ATA is present or not, it may be necessary to switch the patient to a therapy with a different mechanism of action such as the anti-alpha4-beta-7-integrin antibody vedolizumab or the IL12/IL23 antibody ustekinumab.

 

Low trough concentrations may be correlated with loss of response to adalimumab. For adalimumab trough concentrations of 8.0 mcg/mL or less, testing for ATA is suggested. 

For adalimumab trough concentrations above 8.0 mcg/mL, the presence of ATA is unlikely; patients experiencing loss of response to adalimumab may benefit from a therapy with a different mechanism of action such as the anti-alpha4-beta-7-integrin antibody vedolizumab or the IL12/IL23 antibody ustekinumab.

 

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

 

Test interpretation relies on clinical presentation and may differ from the statements above, which were designed for adults with IBD experiencing loss of response. For individuals on adalimumab therapy for other conditions such as rheumatoid arthritis, or pediatric patient populations or proactive monitoring, drug concentration therapeutic targets and patient management decision may be individualized.

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

Tumor necrosis factor (TNF) measurement is not the analyte of choice for monitoring therapy with TNF inhibitors (such as adalimumab or infliximab), since TNF testing would not distinguish between free TNF and TNF bound to the monoclonal antibody, either in the extracellular or membrane-bound form of the cytokine.

 

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

 

Optimal therapeutic concentrations of adalimumab may vary according to the disease.(11-13) For adults with active inflammatory bowel disease, a concentration of 7.5 mcg/mL or greater is considered therapeutic.(5)

 

For patients taking biotin supplements, it is recommended to wait at least 12 hours after the last ingestion of biotin to collect a blood sample for this test.

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

1. Willrich MA, Murray DL, Snyder MR: Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Transl Res. 2015 Feb;165(2):270-282

2. 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

3. Ordas I, Feagan BG, Sandborn WJ: Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1079-1087; quiz e85-86

4. Restellini S, Chao CY, Lakatos PL, et al: Therapeutic drug monitoring guides the management of Crohn's patients with secondary loss of response to adalimumab. Inflamm Bowel Dis. 2018 Jun 8;24(7):1531-1538

5. American Gastroenterological Association: Therapeutic drug monitoring in inflammatory bowel disease: Clinical decision support tool. Gastroenterology. 2017 Sep;153(3):858-859. doi:10.1053/j.gastro.2017.07.039

6. D'Haens GR, Sandborn WJ, Loftus EV Jr, et al: Higher vs standard adalimumab induction dosing regimens and 2 maintenance strategies: Randomized SERENE CD trial results. Gastroenterology. 2022 Feb 3;S0016-5085(22)00099-3. doi: 10.1053/j.gastro.2022.01.044

7. Yao J, Jiang X, You JHS: Proactive therapeutic drug monitoring of adalimumab for pediatric Crohn's disease patients: A cost-effectiveness analysis. J Gastroenterol Hepatol. 2021 Sep;36(9):2397-2407. doi:10.1111/jgh.15373

8. Kato M, Sugimoto K, Ikeya K, et al: Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease. PLoS One. 2021 Jul 9;16(7):e0254548

9. Vande Casteele N, Herfarth H, Katz J, Falck-Ytter Y, Singh S: American Gastroenterological Association Institute technical review on the role of therapeutic drug monitoring in the management of inflammatory bowel diseases. Gastroenterology. 2017 Sep;153(3):835-857.e6. doi: 10.1053/j.gastro.2017.07.031

10. Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S: 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

11. Sejournet L, Kerever S, Mathis T, Kodjikian L, Jamilloux Y, Seve P: Therapeutic drug monitoring guides the management of patients with chronic non-infectious uveitis treated with adalimumab: a retrospective study. Br J Ophthalmol. 2021 Apr 19;bjophthalmol-2021-319072

12. Gomez-Arango C, Gorostiza I, Ucar E, et al: Cost-effectiveness of therapeutic drug monitoring-guided adalimumab therapy in rheumatic diseases: A Prospective, Pragmatic Trial. Rheumatol Ther. 2021 Sep;8(3):1323-1339. doi:10.1007/s40744-021-00345-5

13. Abdalla T, Mansour M, Bouazzi D, Lowes MA, Jemec GBE, Alavi A: Therapeutic drug monitoring in patients with suboptimal response to adalimumab for hidradenitis suppurativa: A retrospective case series. Am J Clin Dermatol. 2021 Mar;22(2):275-283. doi:10.1007/s40257-020-00575-3

Method Description
Describes how the test is performed and provides a method-specific reference

Adalimumab Quantitation:

The adalimumab enzyme-linked immunosorbent assay (ELISA) is designed to determine the quantity of free adalimumab (therapeutic antibody against tumor necrosis factor-alpha: TNF-alpha) in serum samples. In a first incubation step, the free adalimumab from the sample is bound to the specific monoclonal anti-adalimumab antibody coated on the plate. To remove all unbound substances, a washing step is carried out. In a further incubation step, peroxidase-labeled antibody is added. Tetramethylbenzidine (TMB) is used as a substrate for peroxidase. Finally, an acidic stop solution is added to terminate the reaction. The color changes from blue to yellow. The intensity of the yellow color is directly proportional to the concentration of free adalimumab in the sample. A dose response curve of the absorbance unit (optical density: OD) verses concentration is generated, using the values obtained from standard. The concentrations of free adalimumab in the samples are determined directly from this curve.(Package insert: Adalimumab Drug Level ELISA reagent. Immun Diagnostik; KR9657, ver 10/2020)

 

Antibodies to Adalimumab:

This ELISA test serves for the determination of antibodies against TNF-alpha blocker adalimumab (Humira). During sample preparation, the antibodies-to-adalimumab (ATA) are separated from the therapeutic antibody adalimumab using an acid dissociation in order to acquire free ATA. By adding the peroxidase conjugate (POD-therapeutic antibody adalimumab) and the tracer (biotinylated therapeutic antibody adalimumab), the unlabeled therapeutic antibodies are replaced, and the labeled antibodies can form a complex with the ATA. This complex binds via biotin to the streptavidin-coated microtiter plate. It is detected via the peroxidase conjugate with the peroxidase converting the substrate, TMB, to a blue product. The enzymatic reaction is stopped by adding an acidic solution. The samples convert from blue to yellow. The color change should be measured in a photometer at 450 nm. The interpretation is made using the cut-off control.(Package insert: Adalimumab Total ADA ELISA reagent. Immun Diagnostik; KR9651, ver 02/2021)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

80145

83520 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ADALX Adalimumab QN with Reflex to Ab, S 86894-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
ADALX Adalimumab QN with Reflex to Ab, S 86894-3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports