Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's disease
Treatment: Infliximab
The insurer denied the Infliximab.
The determination is overturned in part.

The patient has Crohn's disease. He has severe terminal ileum disease with fistulas. At issue is the medical necessity for infliximab 10 milligrams (mg) /kilogram (kg) for the treatment of Crohn's disease.

The request for infliximab is supported as medically necessary (although the dose requested is not). The patient has moderate to severe Crohn's disease, given the presence of fistulas and diagnosis before age 30. Per the American College of Gastroenterology guidelines for primary therapy, immunosuppressants such as azathioprine, 6-mercaptopurine, and methotrexate are given a weak recommendation (level 2 evidence), and tumor necrosis factor (TNF) inhibitors such as infliximab are strongly recommended (level 1 evidence) [1]. These recommendations are corroborated by the American Gastroenterological Association Guidelines for Initial Medical Treatment in Crohn's Disease [2,3]. For patients with moderate-severe Crohn's Disease, these guidelines state: use anti-TNF monotherapy over no therapy or thiopurine monotherapy (such as immunosuppressants); no other alternatives are recommended - immunosuppressants may take up to 17 weeks to be effective, and aminosalicylates, corticosteroids, and antibiotics are not recommended as long-term primary therapy as they are unlikely to prevent complications [1-4]. The guidelines state that "Thiopurine agents and methotrexate are not effective agents for short-term induction in active, symptomatic disease because of their relatively slow onset of action, between 8 and 12 weeks" and "a disadvantage of the thiopurine analogs and methotrexate is the slow time to clinical response that may not be evident for as long as 12 weeks" [1]. The guidelines state that azathioprine and 6-mercaptopurine are "not more effective than placebo to induce short-term symptomatic remission and should not be used in this manner" and "Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) should be used to treat Crohn's disease that is resistant to treatment with corticosteroids" [1]. In this case, the patient is unlikely to respond to conventional alternatives for induction of remission [1-4]. Comparative trials have shown improvement in outcomes with early initiation of infliximab with azathioprine compared with azathioprine alone, and with initiation of biologic therapy compared with immunomodulators [5-7]. The patient is at risk for Crohn's disease complications such as fistula, stricture, hospitalization, and need for surgery if effective therapy is not initiated; for these reasons, the use of infliximab for the treatment of Crohn's disease is supported as medically per current medical literature. However, initiation of infliximab at the dose requested of 10 mg/kg is not supported by guidelines, and although response can be recovered using 10 mg/kg when remission is lost, initiation at 10 mg/kg is not recommended even in severe disease [1]. The standard dose for initiation of infliximab for the treatment of Crohn's disease is 5 mg/kg at 0, 2, and 6 weeks, and then every 8 weeks.