Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Digestive System/Gastrointestinal/Crohn's Disease.
Treatment: Lab Work/Blood Tests.
The health plan denied the requested therapeutic drug testing of anti-Adalimumab antibodies. 
The health plan's determination is upheld.
 
The patient is a female who was diagnosed with Crohn's disease. After  initial therapy with 6-MP, she began treatment with Adalimumab (Humira). Standard dosing (40 milligrams (mg) every 2 weeks) was escalated to weekly due to worsening terminal ileal inflammation. Despite this, an ileocecal resection was needed due to ileal stenosis. Postoperatively, she once again received alternate-week therapy initially, and Adalimumab trough levels began to be monitored.

Monitoring of Adalimumab (ADL) trough levels resulted in dosing changes  (when a low level resulted in a change back to weekly administration)  when a high trough level allowed another trial of biweekly dosing. A repeat trough ADL level (also with anti-ADL antibody detection) was ordered to monitor for adequacy of therapy and risk of loss of efficacy. It is the measurement of anti-ADL antibodies that is in dispute, based on investigational status for this assay per policy guidelines. The ordering physician is appealing this decision; she lists literature supporting the use of therapeutic drug monitoring for ADL in Crohn's disease.

I uphold, in whole, the health plan's determination.

No, I find no evidence that measurement of anti-Adalimumab (anti-ADL) antibodies is more beneficial than standard treatment.

There have been multiple studies showing the utility of measuring trough blood levels of ADL itself, including the recent prospective PANTS study (Kennedy, et al.) showing a clear association between trough drug levels > 12 micrograms (mcg) /milliliter (mL) and endoscopic remission. Further, measurement of drug levels is being done by the majority of gastroenterologists, as recently documented in New Zealand (Thomas, et al.). Adjusting the dose proactively, based on drug levels, rather than reactively (based on symptoms or disease scores) results in higher rates of remission (Assa, et al.). Although one might expect that detection of anti-ADL antibodies would result in loss of efficacy, there is no clear consensus that measuring these antibodies offers advantages above the measurement of the drug itself. A subanalysis of the DIAMOND trial (Nakase, et al.) confirms that the presence of anti-ADL antibody is associated with low ADL levels and also with loss of remission; these data suggest that the important measurement is of ADL itself, and not of anti-ADL antibodies.

There is yet no published disease society consensus on the utility of anti-ADL monitoring, nor have there been any consensus recommendations on when or how often these should be measured. I can understand the potential utility in the case of loss of response to ADL, with low drug levels despite adequate dosing, in which case anti-ADL may be postulated to be the cause. That was not the case with this patient.
Although the measurement of trough Adalimumab levels is clearly beneficial and is becoming the standard of care, the routine measurement of anti-Adalimumab antibodies is still investigational.