Test ID: USTEK Ustekinumab Quantitation with Antibodies, Serum
Specimen Required
Patient Preparation: Collect immediately before the next dose of drug administration (trough level)
Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Specimen Volume: 0.5 mL
Forms
If not ordering electronically, complete, print, and send a Gastroenterology and Hepatology Client Test Request (T728) with the specimen.
Useful For
Evaluation of loss of response to therapy
Quantification of ustekinumab in human serum
Trough level quantitation for evaluation of patients treated with ustekinumab
Detection of antibodies to ustekinumab in human serum
Profile Information
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
USQN | Ustekinumab QN, S | No | Yes |
USTAB | Ustekinumab Ab, S | No | Yes |
Method Name
Enzyme-Linked Immunosorbent Assay (ELISA)
Reporting Name
Ustekinumab QN with Antibodies, SSpecimen Type
SerumSpecimen Minimum Volume
0.35 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 21 days | |
Frozen | 21 days |
Clinical Information
Ustekinumab (UTK) is a fully human IgG1 kappa monoclonal antibody (1) that binds with high affinity to the p40 subunit of human interleukin (IL)12 and IL23 and has been approved for the treatment of patients with moderate to severe Crohn disease (CD), moderate to severe ulcerative colitis (UC), psoriatic arthritis, and plaque psoriasis. The drug prevents IL12 and IL23 bioactivity by binding and neutralizing the shared p40 subunit, preventing interaction with the cell surface receptor protein IL12Rbeta1. Through this mechanism of action, UTK effectively neutralizes IL12 and IL23, proteins that are thought to be associated with gastrointestinal inflammation in CD and UC. In the setting of the inflammatory bowel diseases (IBD), CD and UC, the treatment regimen is started with a single weight-based loading dose of the t-mab administered intravenously (IV), and a maintenance regimen with standard (non-weight based) subcutaneous administration of ustekinumab 8 weeks after induction dose, and every 8 weeks thereafter. There is very little data supporting proactive therapeutic drug monitoring for ustekinumab.
The test is most useful in the evaluation of loss of response to therapy. A gradual decrease in efficacy over time following an initial response to biologics is common. In many cases, antibodies generated to the biologic are responsible for treatment failure, as they bind to the drug creating an immunocomplex and clearing the drug faster from circulation.
For IBD, measurements in nonresponders are indicated at post-induction (week 8) and concentrations of ustekinumab associated with favorable outcomes are greater than 3.5 mcg/mL. In addition, for measurements during maintenance stages of therapy, ustekinumab concentrations ≥1 mcg/mL are associated with clinical response and clinical remission. At maintenance stages, ustekinumab concentrations ≥4.5 mcg/mL are associated with mucosal healing.
In clinical trials, 6% to 12.4% of patients using ustekinumab for psoriasis or psoriatic arthritis developed antibodies-to-ustekinumab (ATU) over time. For IBD, between 2.9% and 4.6% of patients developed ATU when treated with ustekinumab for one year.(1) Therefore, it is important to monitor trough concentrations of serum UTK to correlate drug levels with loss of response to therapy. ATU may increase drug clearance in treated patients or neutralize the drug effect, thereby potentially contributing to the loss of response. ATU could also cause adverse events such as serum sickness and hypersensitivity reactions.
Currently, ustekinumab quantitation is performed in conjunction with immunogenicity assessment for ATU.
Reference Values
USTEKINUMAB QN, S:
Limit of quantitation is 0.3 mcg/mL
In inflammatory bowel disease, at post-induction measurement (week 8), concentrations above 3.5 mcg/mL are associated with good outcomes
For maintenance stages:
Concentrations ≥1.0 mcg/mL are associated with clinical response and clinical remission
Concentrations ≥4.5 mcg/mL are associated with mucosal healing
USTEKINUMAB AB, S:
Limit of quantitation is 10 AU/mL
Absent: <10 AU/mL
Present: ≥10 AU/mL
Interpretation
Antibodies to ustekinumab (ATU) absent |
ATU present |
|
Ustekinumab quantification <1.0 mcg/mL |
For nonresponders: Insufficient ustekinumab is present.
In the absence of ATU, consider optimizing therapy by increasing the dose or shortening the administration intervals, or by adding an immunomodulator to the therapeutic regimen. |
For nonresponders: Insufficient ustekinumab is present. Antibodies-to-ustekinumab detected can contribute to faster clearance of ustekinumab and treatment failure. Clinical evaluation is recommended. |
Ustekinumab quantification ≥1.0 mcg/mL |
For nonresponders: If the sample was collected at trough ie, immediately before the next infusion, the results could suggest a mechanistic failure of ustekinumab. The provider may consider switching therapeutic regimen outside of the drug class. |
For nonresponders:
If the sample was collected at trough ie, immediately before the next infusion, the results could suggest a mechanistic failure of ustekinumab. The provider may consider switching therapeutic regimen outside of the drug class. |
Clinical Reference
1. Stelara (ustekinumab). Package insert: Prescribing information. Janssen Pharmaceuticals; revised 03/2020
2. Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2019;17:1655-68 e3
Day(s) and Time(s) Performed
Tuesday, Friday; 11:00 a.m.
Analytic Time
1 dayTest 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 U.S. Food and Drug Administration.CPT Code Information
8029983520
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
USTEK | Ustekinumab QN with Antibodies, S | In Process |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
USQN | Ustekinumab QN, S | 87408-1 |
USTAB | Ustekinumab Ab, S | 87409-9 |
mml-gi-ibd-tdm