Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Complex ileocolonic Crohn's disease
Treatment: Lab testing for serum measurement of serum antibodies to tumor
necrosis blockers due to adalimumab (80145)
The insurer denied the Lab testing for serum measurement of serum antibodies to
tumor necrosis blockers due to adalimumab (80145)
The denial is upheld.

This patient is a female with Crohn's disease on Humira, increasing to weekly. The
patient had therapeutic drug monitoring (Humira levels and antibodies to Humira).

No, the health plan should not cover the proposed lab testing for serum
measurement of serum antibodies to tumor necrosis blockers due to adalimumab
(80145).
Infliximab and adalimumab are both anti-tumor necrosis factor (TNF) alpha agents
used in the treatment of inflammatory bowel disease. The Prometheus Anser
ADA(adalimumab) test, which was launched, follows the much earlier introduction
of the Prometheus Anser IFX (Infliximab) test. These tests are assays that can
measure both infliximab or adalimumab and antibody levels from one serum
sample.

Checking antibodies to adalimumab have been studied as follows:
1) In a study, 118 serum samples were included from 71 patients, adalimumab drug
and antibody levels were looked at in patients with Crohn's disease (Mazor Y et al.
Aliment Pharmacol Ther). The group found that high adalimumab trough serum
concentration was associated with disease remission and the optimal sensitivity
was with a cut-off drug level of 5.85 micrograms per milliliter. Similarly, high levels
of anti-adalimumab antibodies were positively associated with disease activity.

2) In another retrospective study looking at adult and pediatric patients, in the 247
patients (42 with ulcerative colitis), there were 330 loss of response events (188 to
infliximab and 142 to adalimumab). Adalimumab levels of greater than 4.5
micrograms per milliliter and infliximab levels greater than 3.8 micrograms per
milliliter identified patients who failed to respond to an increase in drug dosage or a
switch to another anti-tumor necrosis factor (TNF) agent with 90% (percent) specificity (Yanai H et al. Clin Gastroenterol Hepatol.).

3) A prospective study included all consecutive patients with inflammatory bowel
disease (IBD) having a disease flare while being on adalimumab 40 milligrams (mg)
every two weeks. All patients were primary responders to adalimumab therapy and
were anti-tumor necrosis factor (TNF) naive. Adalimumab trough levels and
antibodies against were measured blinded to clinical data. Patients were divided
into three groups based on adalimumab trough levels and based on previous
studies: group A, ADA (adalimumab) greater than 4.9 micrograms per milliliter
(ug/ml); group B, ADA (adalimumab) less than (<) 4.9 micrograms per milliliter
(ug/ml) and undetectable levels of antibodies against adalimumab (less than ten
nanograms per milliliter); and group C, ADA (adalimumab) less than 4.9
micrograms per milliliter and antibodies against adalimumab greater than ten
nanograms per milliliter. The response to ADA (adalimumab) optimization was
significantly more durable in group B (15 months) than in groups A and C (four and
five months, respectively) (Roblin X et al. Am J Gastroenterol.).

Physicians should perform reactive therapeutic drug monitoring to guide changes in
antitumor necrosis factor (TNF) therapy in patients with active inflammatory bowel
disease and should consider target trough concentrations of at least five
micrograms per milliliter for infliximab, at least 7.5 micrograms per milliliter for
adalimumab, and at least 20 micrograms per milliliter for certolizumab pegol,
according to a guideline from the American Gastroenterological Association (AGA)
Institute (Feuerstein JD, et al. Gastroenterology.).

Guidance from the American Gastroenterological Association is as follows: "If the
trough concentration is low (below the suggested threshold, in patients with active
IBD) and no anti-drug antibodies are present, then the index drug should be
optimized using any of the following techniques: shortening the dosing interval
and/or increasing the drug dose, and/or adding an immunomodulator agent."

As the documentation does not support increased signs / symptoms of disease at
the time of the service, the service was not medically necessary.

No, the requested health service or treatment is not more beneficial than any
standard treatment for the insured's condition or disease.
Standard of care would be to monitor signs / symptoms of disease.