Appeal type: Experimental/Investigational
Decision: Upheld

Reviewer #3

Diagnosis: Crohn's disease

Treatment: Adalimumab/Humira [citrate-free (cf)] 80 milligrams (mg)

The insurer denied coverage for Adalimumab/Humira (cf) 80 mg

The denial is upheld

According to the medical records, the patient is a male with Crohn's disease. The patient was started on adalimumab 40mg every two weeks. The patient had a follow-up appointment and stated he was having fatigue, abdominal pain and loose stools. His adalimumab level was noted to be 1.6. His adalimumab was increased to 40mg every week. He was started on Prednisone as well. One month after his Prednisone was stopped, he was noted to have bright red blood per rectum. His Prednisone was restarted. The plan is to increase his adalimumab to 80mg every week.

There is evidence to show that dose escalation of adalimumab in patients who do not have antibodies to adalimumab and subtherapeutic levels can receive dose escalation which will result in clinical efficacy. However, it is not clear in this case if dose escalation will be beneficial.      

Even though the regulatory bodies do not approve this dose. It does not need to have approval since there is scientific evidence published in peer reviewed journals that show clinical efficacy. Before this approved, antibodies to adalimumab need to be drawn.     

The patient did have an initial response, but then lost response to adalimumab. The patient is also noted to have evidence of ongoing symptoms most likely secondary to his Crohn's disease. The patient does not have evidence data regarding the presence of antibodies to adalimumab. This needs to be obtained before dose escalation occurs.     

It is not clear if this is the best available treatment. Dose escalation may be beneficial since the patient initially responded to adalimumab and is noted to subtherapeutic doses of adalimumab. However, there is no evidence that antibodies of adalimumab were drawn.     
  
There are adverse risks with dose escalation. These risks include but are limited to, injection site reactions, increased infection risk, risk of congestive heart failure and development of bone marrow suppression.     

Since the patient initially responded to adalimumab and then lost response and does not have detectable levels of the medication, there needs to be more information to determine why this happened. There is no evidence that antibodies to adalimumab were obtained. This could cause a loss of efficacy. Based on this it cannot be said this dosage is likely to be more beneficial.

"Conclusions: Our results emphasize the relevance of therapeutic drug monitoring in Crohn's disease patients on biologic treatment. Adalimumab (ADA) trough serum levels and the presence of anti-ADA antibody (AAA) are important features in the management of patients on ADA treatment." (Bodini, G. et al. 2016)

"Conclusion The available evidence suggests that these tests have modest predictive accuracy for clinical status; direct test accuracy comparisons in the same population are needed. More clinical trial evidence from test-treat studies is required before the clinical utility of the tests can be reliably evaluated." (Freeman, K. et al. 2017)

"Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease." (Lichtenstein, G. R. et al. 2018)    

The requested service is not likely to be more beneficial than any of the standard treatments/procedures for this patient.

The carrier's denial of Adalimumab/Humira (cf) 80 mg should be upheld.