Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Inflammatory bowel disease (IBD).

Treatment: current procedural terminology code (CPT) 80145, adalimumab serum levels and antibodies to adalimumab

The insurer denied coverage for current procedural terminology code (CPT) 80145, adalimumab serum levels and antibodies to adalimumab

The denial is overturned

The patient has a past medical history notable for Crohn's disease of the large and small intestine being treated with adalimumab. There are no details regarding his diagnosis other than a notation that he underwent esophagogastroduodenoscopy (EGD) and colonoscopy. According to an office visit note, his current dose is 40mg (milligrams) subcutaneous (SQ) every (q) 14 days. His weight on was 57.6 kilograms and his height was 168.5 centimeters. He had no gastrointestinal symptoms to suggest active disease and his physical exam was normal.

As part of his care, laboratories studies were obtained that included a c-reactive protein (CRP) <1, erythrocyte sedimentation rate (ESR) 2, adalimumab trough level 7 and adalimumab anti-drug antibodies that were undetectable. Prior adalimumab level was 11 . No documentation in change in management was noted based on the levels obtained.   

This patient has Crohn's disease (CD) on treatment with adalimumab. The assay used to monitor drug levels proactively in this case (without clinical evidence of active disease or loss of efficacy) was the Prometheus Anser Assay. This a propriety, non-radiolabeled, fluid-phase mobility shift assay that Prometheus has marketed as superior to the more traditional solid phase ELISA methods. In an overview of the medical therapies for Crohn's disease in children and adolescents from UptoDate the authors state the following:

	First-line biologic agents - Infliximab and adalimumab are monoclonal antibodies directed against tumor necrosis factor (TNF). These drugs are important options for patients with moderate or severe CD and have become the mainstay of induction and maintenance treatment for CD in North America and Europe 
	Adalimumab is a humanized antibody, whereas infliximab is a chimeric antibody.
	Dose and administration - Adalimumab is administered by subcutaneous injection every two weeks. For adults and children >=40 kg body weight, the manufacturer's label recommends a loading dose of 160 mg, followed by 80 mg (milligrams) two weeks later, and 40 mg every two weeks for maintenance. For children 17 to 40 kg (kilograms) body weight, the loading dose is 80 mg, followed by 40 mg two weeks later, and 20 mg every two weeks for maintenance. Escalation to weekly dosing is often necessary, guided by therapeutic drug monitoring and/or the clinical response.
	Therapeutic drug monitoring - trough levels and anti-drug antibodies are increasingly being utilized to monitor patients receiving anti-tumor necrosis factor (TNF) therapy and to optimize dosing for each patient, although the optimal way to monitor patients has not yet been determined and the monitoring is costly. Several studies suggest concentrations above certain thresholds are associated with a higher likelihood of remission in adults and children and other studies support the use of higher thresholds and/or earlier monitoring 

There is a beneficial role of drug monitoring both reactive and proactive in optimizing and personalizing treatment with biological agents. The cost of empirically raising biological dosing in the setting of loss of response was greater than drug monitored dosing. This patient clearly had sustained response to adalimumab by clinical measures and inflammatory markers. He has not had recent evaluation for mucosal healing that appears to correlate better with levels than with clinical factors. 

In conclusion, therapeutic drug monitoring is more beneficial than prior methods to adjust biological therapy for Crohn's disease. 

The requested therapy is likely to be more beneficial than any other standard procedures. The adverse risks are not increased over standard therapies.

The carrier's denial of current procedural terminology code (CPT) 80145, adalimumab serum levels and antibodies to adalimumab should be overturned.