Laboratory Testing for Monoclonal Antibody Therapeutics

Indications for Testing

Laboratory monitoring for monoclonal antibody therapeutics is appropriate in individuals receiving monoclonal antibody drugs (eg, adalimumab, infliximab). Laboratory monitoring can be used to optimize dosage or investigate treatment failure:

• Primary treatment failure occurs when a patient does not initially respond to therapy. ^, , 
• Secondary treatment failure occurs when there is a loss of previous response. ^, ,  This failure is often due to the presence of antidrug antibodies. ^, 

Refer to the Monitoring Strategies section for more detailed information about test timing.

Laboratory Testing

Monoclonal antibody therapeutic drug monitoring primarily involves two types of laboratory testing: drug concentration measurement and antidrug antibody detection.

Drug Concentration Testing

Drug concentration testing is used to assess the exact concentration of a biologic drug in a patient’s serum. Test methods include binding assays such as enzyme-linked immunosorbent assays (ELISAs) and high-mobility shift assays; functional assays such as cell-based reporter genes assays; and liquid chromatography-tandem mass spectrometry (LC-MS/MS). ^,  This testing is used to determine whether the drug concentration falls within a specified therapeutic range: a lower concentration might render the drug ineffective, whereas exceeding the range might not offer added therapeutic benefits and may increase the risk of side effects.

Antidrug Antibody Testing

Monoclonal antibodies are (to a varying degree) immunogenic (ie, repeated use of a given monoclonal antibody drug may lead to the development of antidrug antibodies by the patient’s immune system). ^,  These antibodies may interfere with drug function by neutralizing the drug or increasing its clearance, potentially resulting in treatment failure. ^,  These antibodies may also trigger adverse reactions to the drug.  However, not all antidrug antibodies have direct clinical implications; antidrug antibody test results should be interpreted in the complete clinical context.

Standard methods for antidrug antibody detection include ELISAs, high-mobility shift assays, and cell-based reporter gene assays. ^,  LC-MS/MS is not used to assess for antidrug antibodies. 

Monitoring Strategies

Two strategies are commonly used to monitor monoclonal antibody therapeutics:

• Reactive monitoring is used to assess drug and/or antidrug antibody levels in response to a clinical event or symptom, typically a lack or loss of response (primary or secondary treatment failure), exacerbation of disease, or the development of adverse reactions. ^, 
• Proactive monitoring is used to assess drug and/or antidrug antibody levels with the goal of optimizing the dosage for an individual patient. 

Reactive Monitoring

The standard strategy for reactive monitoring typically involves measurement of trough serum drug concentrations simultaneously with antidrug antibodies. ^,  Results from these tests, in the context of the complete clinical scenario, can inform the management strategy. This approach has been systematically evaluated in the context of anti-TNF treatment for inflammatory bowel disease. ^, , , , 

Proactive Drug Monitoring

Proactive drug monitoring entails regular laboratory testing for drug and/or antidrug antibody concentrations, regardless of the patient's clinical status, to individually optimize dosage.  Cheifetz et al  propose the following regarding the role of proactive drug monitoring for anti-TNF monoclonal antibody therapeutics (eg, adalimumab, infliximab):

• Proactive drug monitoring of anti-TNF drugs should be performed after induction, at least one time during maintenance, and after reactive drug monitoring.
• Proactive drug monitoring is most consequential for patients with high drug clearance or severely active disease.
• Proactive drug monitoring to optimize anti-TNF monotherapy leads to better outcomes than unoptimized therapy.
• Proactive drug monitoring to optimize anti-TNF monotherapy may be a useful alternative to combination anti-TNF therapy in some situations.
• The same assay should be used for longitudinal proactive drug monitoring unless different assays have been fully standardized and cross-validated.

More studies are needed to support the use of proactive drug monitoring for other monoclonal antibody treatments. 

Interference With Laboratory Tests

Monoclonal antibody therapeutics have the potential to interfere with laboratory testing, including blood bank testing, monoclonal protein testing, and solid organ transplantation testing.  These interferences can have adverse effects on clinical care and may lead to unneeded additional testing.  The specific nature of the interference depends on the monoclonal antibody therapeutic, as do the techniques for addressing interference.  Consultation with the laboratory is advisable if interference is suspected. Careful communication is also advised to ensure that the laboratory is aware of the presence or possible presence of monoclonal antibody therapeutics.