Ustekinumab (UTK) is a fully human IgG1 kappa monoclonal antibody 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. 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.