Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Digestive System/Gastrointestinal/Crohn's Disease.
Treatment: Pharmacy/Prescription Drugs/Stelara.
The health plan denied the requested medication, Stelara, as experimental/investigational. 
The health plan's determination is overturned.

The patient is a female under evaluation and management for Crohn's Disease (CD). The patient has a history of fistulizing disease with perianal involvement and has previously failed anti-tumor necrosis factor (TNF) agents including Humira and Remicade. As an aside, she also has hidradenitis suppurative. She was placed on Stelara 90 milligrams (mg) SC (subcutaneous) for 8 weeks and did have a significant response. At an office visit, the patient was documented to be having a good response to this therapy. A colonoscopy demonstrated active ileal and colonic ulcerations however her peri-anal fistulizing disease was healed. Fecal calpro was elevated to 193. Based on this data, it was felt that a higher dose of Stelara was indicated.
The patient's provider has requested Stelara at 90 mg SC every 4 weeks rather than every 8 weeks, which is the approved dose for Crohn's Disease. Every 4-week dosing is considered experimental/investigational.

I recommend overturning, on the whole, the health plan's determination regarding the proposed treatment.

Yes. The request to increase the dosing of Stelara to every 4 weeks is medically necessary and is evidence-based. The patient has already tried and failed all other classes of biologics for the treatment of Crohn's disease. Specifically, the patient can no longer be treated with an anti-TNF drug. The patient has ongoing, clinically active disease despite the use of ustekinumab at conventional dosing.
The best data for the relationship between Stelara drug levels comes from Adedokun, et al. In their analysis of data from Phase 3 studies of patients with moderate to severe CD, they found serum concentrations of ustekinumab to be proportional to dose and associated with treatment efficacy. Trough concentrations of ustekinumab up to 1.4 g/mL (microgram/milliliter) or greater were associated with maintenance of clinical remission in a higher proportion of patients than patients with lower trough concentrations. The study by Battat et al. found that a higher level was associated with efficacy. Patients received 90 mg of ustekinumab subcutaneously at weeks 0, 1, and 2 during induction and 90 mg every 4- or 8 weeks during maintenance. The authors found that the mean trough concentration of ustekinumab at week 26 was higher in patients with an endoscopic response (4.7 g/mL) than without (3.8 ug/mL; (P (statistical significance) = .03). An optimal ustekinumab threshold trough concentration at week 26 or later was found to be 4.5 g/mL (area under the curve, 0.67). A greater proportion of patients with trough concentrations of ustekinumab above 4.5  g/mL at week 26 or later had an endoscopic response (75.9%) than did patients with trough concentrations below this level (40.7%; P = .008). Patients with trough concentrations of ustekinumab above 4.5 g/mL at week 26 or later also had a lower mean level of C-reactive protein (CRP) (12.6 mg/L) than did patients with trough concentrations below this level (mean level of CRP, 23.9 mg/L (milligrams/liter); P = .04).
Based on the above data, I recommend approval of Stelara at every 4-week dosing due to ongoing active disease. The only other option would be to stop Stelara and start Entyvio, however, the efficacy data for Entyvio in the subset of patients with Crohn's Disease who have failed an anti-TNF is poor.