TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: USTEK    
Ustekinumab Quantitation with Antibodies, Serum

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

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

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

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 > or =1 mcg/mL are associated with clinical response and clinical remission. At maintenance stages, ustekinumab concentrations > or =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 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.

USTEKINUMAB QN, S:

Limit of quantitation is 0.3 mcg/mL

 

In inflammatory bowel disease, at post-induction measurement (week 8), concentrations above3.5 mcg/mL are associated with good outcomes

 

For maintenance stages:

Concentrations > or =1.0 mcg/mL are associated with clinical response and clinical remission

Concentrations > or =4.5 mcg/mL are associated with mucosal healing

 

USTEKINUMAB AB, S:

Limit of quantitation is 10 AU/mL

Absent: <10 AU/mL

Present: > or =10 AU/mL

Interpretation Provides information to assist in interpretation of the test results

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

> or =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.

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

This assay measures free ustekinumab. This assay does not measure ustekinumab bound to anti-ustekinumab antibodies (immunocomplexes).

 

Presence of ustekinumab at concentrations greater than 1 mcg/mL may impair detection of antibodies to ustekinumab (ATU), as the ATU assay is not drug tolerant. This assay measures free ATU. This assay does not measure ATU bound to UTK (immunocomplexes).

 

Elevated rheumatoid factor (RF) may falsely increase results of ATU. During validation studies, negative ATU samples remained negative and positive ATU samples remained positive; however the quantitative result differed by more than 20% when compared to the non-RF spiked original samples. If patients are positive for RF, clinical correlation is recommended for ATU test interpretation.

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

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