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
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
USQN | Ustekinumab QN, S | No | Yes |
USTAB | Ustekinumab Ab, S | No | Yes |
Enzyme-Linked Immunosorbent Assay (ELISA)
Stelara
Stelara antibodies
Serum
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
If not ordering electronically, complete, print, and send 1 of the following with the specimen:
-Gastroenterology and Hepatology Client Test Request (T728)
-Therapeutics Test Request (T831)
0.35 mL
Gross hemolysis | Reject |
Gross lipemia | Reject |
Heat-inactivated specimen | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 21 days | |
Frozen | 21 days |
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
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.
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 > 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
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. |
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.
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
Monday, Thursday
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.
83520
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
USTEK | Ustekinumab QN with Antibodies, S | In Process |
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.
|
---|---|---|
USQN | Ustekinumab QN, S | 87408-1 |
USTAB | Ustekinumab Ab, S | 87409-9 |