Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease. 
Treatment: Stelara 

The insurer denied the Stelara. 
The denial is overturned. 

This is a male with Crohn's disease having ileitis and a stricture.  His symptoms improved with a steroid taper.  The patient has sacral ileitis and has failed Inflectra and Humira.  The request is for Stelara.  The patient has extra-intestinal manifestations of Crohn's disease. 

Yes, the health plan should cover the proposed treatment with Stelara. 

Vedolizumab is a drug that specifically targets the alpha four beta seven integrin that is selectively expressed on gut-homing T lymphocytes. The U.S. Food and Drug Administration (FDA) approved Entyvio (Vedolizumab) to treat adult patients with moderate to severe ulcerative colitis and adult patients with moderate to severe Crohn's disease. Vedolizumab's use in Crohn's disease has been studied in a randomized, double-blind, placebo-controlled Phase III trial (GEMINI II trial). Fifteen percent in the Vedolizumab group compared to 7% (percent) of placebo group, achieved clinical remission at week six, clinical remission defined as having a CDAI score = 150 points. The patients in the Vedolizumab group did not have a significant difference in response rates when compared to placebo at 6 weeks, response being defined as a 100 point decrease in Clinical Disease Activity Index (CDAI) from baseline. In the maintenance phase of the trial, the primary end point was clinical remission at week 52. Patients received eight weekly Vedolizumab, four weekly Vedolizumab, or placebo. Eight weekly Vedolizumab had remission rates of 39%, four weekly Vedolizumab had remission rates of 36%, and placebo patients had remission rates of 22%. The difference was statistically significant when comparing the drug groups with placebo. 

Stelara (ustekinumab) was Food and Drug Administration (FDA) approved for use in Crohn's disease. The drug was previously Food and Drug Administration approved for a diagnosis of psoriasis. Ustekinumab is a humanized immunoglobulin G monoclonal antibody targeting interleukin IL-12 and IL-23. They in turn thereby inhibit their receptors on T cells, natural killer cells, and antigen-presenting cells. In a phase IIa study (Sandborn WJ, Gastroenterology), it was shown that patients on ustekinumab had higher response rates (53%) at weeks four and eight compared to patients on placebo (30%). In a phase IIb randomized, double-blind, placebo-controlled trial (Sandborn WJ, NEJM), patients with moderate-to-severe Crohn's disease who failed prior anti-tumor necrosis factor (TNF) therapy had significantly greater clinical response to ustekinumab (39.7%) at week six compared to the placebo group (23.5%). In the New England Journal of Medicine (NEJM) article (Sandborn), the design of the study included an induction phase (weeks 08) followed by a maintenance phase (weeks 836). During the induction phase, subjects were randomly received one-time dose of intravenous placebo or ustekinumab at one, three, or six milligrams per kilogram (mg/kg). During the maintenance phase, subjects were randomized to receive subcutaneous ustekinumab at a dose of 90 milligrams (mg) or placebo at weeks eight and 16. Subjects who responded to placebo continued to get placebo at weeks eight and 16 and those who did not respond to initial placebo, received subcutaneous ustekinumab at a dose of 270 milligrams at week eight and 90 milligrams at week 16.  As stated in the article, "the proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo". 

The request is for Stelara.  The formulary alternative is Entyvio.  There is medical necessity of Stelara over Entyvio in this case given that the patient has extra-intestinal manifestations of Crohn's disease including joint pain for which Stelara would be more beneficial.  Stelara has Food and Drug Administration approved indications for inflammatory bowel disease as well as psoriatic arthritis and indicated efficacy in arthritis whereas Entyvio has an indication for inflammatory bowel disease only.