Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Crohn's disease.
Treatment: Adalimumab testing.

The insurer denied Adalimumab testing.  The determination is upheld.

The patient has Crohn's ileo-colitis. He has previously been treated with Infliximab, and is currently receiving Lialda, Methotrexate, and Adalimumab. He had been receiving adalimumab every 2 weeks; however, he had a flare. His Adalimumab level was 3.2 micrograms per milliliter (mcg/ml), and he did not have any antibodies. The dosage of Adalimumab was increased to every week. His C-reactive protein (CRP) was 14, and fecal calprotectin was 507. His albumin is 4.2, and hemoglobin 14.2. He had a colonoscopy revealing mild Crohn's colitis and external hemorrhoids. He was feeling much better on weekly Adalimumab, denied any abdominal pain, and was having 4 bowel movements daily with occasional hematochezia. He had an Adalimumab level checked revealing a level of 9.4 mcg/ml, and no antibodies were present. His body mass index (BMI) is 27.66. At issue is whether the proposed health service or treatment Adalimumab testing was likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.

The patient has Crohn's ileo-colitis and had a clinical flare. At that time, he had an Adalimumab level evaluated revealing that it was low [3.2 mcg/ml], and a dosage escalation was performed. Afterward, the patient was in clinical remission, did not have any abdominal pain, and felt much better. A colonoscopy revealed mild Crohn's colitis. A second Adalimumab level was checked proactively revealing a higher concentration of Adalimumab [9.4 mcg/ml]. The proactive evaluation of the Adalimumab level was not medically necessary in a patient in clinical remission and was not likely to be more beneficial than standard treatment. This is supported by current evidence-based, peer-reviewed medical literature.

"The frequency with which therapeutic drug monitoring (TDM) needs to be repeated for routine proactive TDM and after a drug-dosing change is also unclear. The cost associated with this is variable based on the different assay costs, as well as downstream costs of treatment changes. Additional well-designed randomized controlled trial (RCTs) with direct patient-relevant outcomes from routine proactive TDM compared with no TDM are still needed to answer whether routine proactive TDM should be performed and, if it is performed, how often TDM should be checked." [1]

"Despite increasing adoption of TDM in clinical practice, there is limited synthesis of evidence and a lack of guidance on the benefits, risks, and overall approach to TDM in the management of IBD. TDM is performed through a blood test generally just before next due dose, which can cause a small inconvenience. However, there are additional potential harms of downstream interventions from TDM testing because thresholds for therapeutic trough concentration and antidrug antibodies (ADAbs) are not very well-defined. Therapeutic trough is dynamic, depending on phase of intervention (induction versus (vs) maintenance therapy), treatment target (clinical remission vs endoscopic remission), and phase of disease activity (severe active vs mild active disease; luminal disease vs perianal disease). Likewise, threshold ADAb levels that define immunogenicity and predict low likelihood of response to dose escalation are not well-defined and are variable across assays. Therefore, due to variable thresholds, which have suboptimal discriminatory performance, strict adherence to TDM-guided treatment changes can potentially result in inappropriate treatment changes in some patients who might have responded to empiric escalation of therapy. Routine proactive TDM can impose modest inconvenience and be expensive due to repeated testing. The feasibility of such an approach for drugs administered subcutaneously every 2-4 weeks is unclear. In addition, because target thresholds are poorly defined, inconsistent, and can vary depending on individual patient or targeted outcome, proactive TDM may lead to inappropriate treatment changes and therapeutic dilemmas in patients otherwise in remission. But there is a lack of prospective interventional data assessing the value of proactive TDM during induction to increase remission rates by targeting threshold drug concentrations." [2]

"Data on benefits of proactive TDM over empiric dosing or reactive TDM are mixed, making recommending a regular interval for repeating TDM among patients who maintain response difficult." [3].