Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Ulcerative Colitis
Treatment: Laboratory Services (80230 - infliximab antibody testing) 
The insurer denied the Laboratory Services (80230 - infliximab antibody testing).
The denial is upheld. 

The patient is a female with pan-ulcerative colitis. She has been maintained on Inflectra (infliximab biosimilar) every eight weeks. 

Per the patient's statement, she underwent therapeutic drug monitoring (TDM) as "a valuable tool to the MD to use for management of patient's disease." No mention was made, either subjective or by objective criteria, of the patient's clinical condition at the time of the TDM (therapeutic drug monitoring) assay.

Results of the patient's therapeutic drug monitoring showed detectable but low serum infliximab (3.7 ug/mL [microgram per milliliter], negative <0.4 ug/mL [microgram per milliliter]) and detectable anti-infliximab antibodies (225 ng/mL [nanogram per milliliter], negative <22 ng/mL [nanogram per milliliter]). How these results impacted the patient's clinical outcome were not provided.

No, the health plan should not cover the Laboratory Services (80230 - infliximab antibody testing).

No, the Laboratory Services (80230 - infliximab antibody testing) is not likely to be more beneficial.

Generally, diminished or suboptimal response to infliximab can be managed in several ways: shortening the interval between doses, increasing the dose, switching to a different anti-TNF (tumor necrosis factor) agent (in patients who continue to have loss of response after receiving the increased dose), or switching to a non-anti-TNF (tumor necrosis factor) agent based on clinical observation in lieu of therapeutic drug monitoring (TDM). Whereas some evidence exists that low serum levels of infliximab and/or the presence of antibodies to infliximab may play a role in primary or secondary response failures.

Antidrug antibodies develop in a substantial number of patients and may be responsible for acute drug infusion reactions as well as delayed hypersensitivity reactions. In a large percent of patients who develop antibodies, such antibodies may disappear after continued treatment. The reasons for therapeutic failures remain unclear.  Some evidence exists that low serum levels of infliximab or adalimumab or the presence of IFX (infliximab) or ADA (adalimumab) antibodies have an adverse effect on the clinical outcome of a patient's response to treatment. While however there have been testimonials, there are few well controlled clinical trials to confirm that use of TDM (therapeutic drug monitoring) leads to improved patient outcomes or quality of life as opposed to the standard method of treatment. (1, 2) 

As in the case of other anti-TNF (tumor necrosis factor) therapy, "in patients with IBD [inflammatory bowel disease] who lose response to infliximab, clinical improvement may occur upon intensification of infliximab therapy, irrespective of infliximab serum concentration or presence of antibodies to infliximab." (4)  As such, the clinical utility of measuring drug antibody concentrations has not been established, and it has not been established how patient management would change based on test results. Limited retrospective evidence describes changes in management after measurement to anti-drug antibodies, but does not compare these management changes to those made in the absence of anti-drug antibody measurement. (6)

Specific to the patient's case, it has not yet been established whether the use of threshold levels aid in the discrimination of treatment response, nor has the optimal timing of when to measure antibody levels been established.

The American Gastroenterological Association (AGA) issued new guideline recommendations on therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD) treated with anti-TNF (tumor necrosis factor) agents and thiopurines.  Pertinent to this review, AGA (American Gastroenterological Association) conditionally suggested use of reactive TDM (therapeutic drug monitoring) to guide treatment changes in patients with active IBD (inflammatory bowel disease) but acknowledged there currently exist no defined cut-offs by which to judge low versus high titer anti-drug antibodies. AGA (American Gastroenterological Association) avoided sanctioning routine proactive TDM (therapeutic drug monitoring) of anti-TNF (tumor necrosis factor) therapy in patients with quiescent IBD (inflammatory bowel disease). (8)  

Certainly, the contemporary medical literature is replete with both proponents and detractors of routine TDM (therapeutic drug monitoring) assay under review. (9) However, in the patient's case, the records do not support that the testing was done in a manner that would be supported by the above-mentioned American Gastroenterological Association guidance.  As such, TDM (therapeutic drug monitoring) neither meets the spirit of AGA (American Gastroenterological Association) guidance above, nor can be considered standard of care or medically appropriate in the patient's routine management.