Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Crohn's disease
Treatment: Blood test to measure level of the drug infliximab, Remicade and body's reaction to the drug (antibodies) 
The insurer denied Blood test to measure level of the drug infliximab, Remicade and body's reaction to the drug (antibodies) 
The determination is upheld.

This is a female patient who has Crohn's disease (CD), managed with Remicade (infliximab) infusions and 6-Mercaptopurine. Her attending provider ordered serum infliximab levels and antibodies to infliximab to determine if the patient had adequate trough levels of infliximab or antibodies to infliximab. The medical records provided do not indicate the rationale for the test or how the results of the test were used to change the management of this patient. At issue is whether the proposed testing is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.

The proposed health service or treatment blood test to measure level of the drug infliximab, Remicade and body's reaction to the drug (antibodies) was not likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.

Tumor necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel disease (IBD), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. It is now established that the development of antibodies to infliximab (ATIs) and low serum drug concentrations are associated with worse clinical outcomes. As current treatment options in TNF-antagonist failures remain limited, emphasis has been placed on rational decision- making based on therapeutic drug monitoring. Although evidence from prospective controlled trials that definitively demonstrate the benefits of therapeutic drug monitoring in IBD is lacking, acceptance of its value in clinical practice is increasing. This test should be used judiciously. Therefore, incorporation of therapeutic drug monitoring into clinical practice may allow clinicians to optimize treatment by maintaining effective drug concentrations over time. The test is useful to the physician when patients on anti-TNF agents show a decreased response to the medication. Although empiric dose optimization or switching agents are sometimes done for secondary failure, these interventions have not been applied in an evidence-based manner.

Therapeutic drug monitoring offers a rational approach to the management of secondary failure to infliximab (IFX). This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomized controlled trials. New data support the use of therapeutic drug monitoring in patients with inflammatory bowel disease. However, these tests should only be checked if the patient is not doing well on therapy. These tests are especially important in patients who are compliant and also important as a guide when considering switching to a different therapy.

Published data support the use of infliximab levels and antibodies to infliximab (ATIs) in patients with inflammatory bowel disease with decreased response to infliximab as the presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Favorable clinical outcome appears to be the consequence of sustained therapeutic drug levels, and the current literature supports a practice of dose adjustments. When immunogenicity develops to a single biological agent, response can be regained by introduction of an alternative biological agent of the same or different class. Efficacy is reduced with second-line agents either within or across classes compared with naive patients. In the absence of direct measurement of drug levels and anti-drug antibodies, clinical judgment is necessary to assess the mechanisms of loss of response, and more empiric decision making may be necessary to determine the choice of second-line biological agents.