Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Digestive System/Gastrointestinal. 
Treatment: pharmacy/prescription drugs. 
The insurer denied: Stelara 90mg/ml every 4 weeks. 
The health plan's determination is overturned. 

The patient is a male with Crohn's disease. The patient had an ileocolic resection along with a sigmoid resection due to areas of active disease/fistulization/stricturing. The patient has been on intravenous (IV) and subcutaneous (SQ) anti-tumor necrosis factor (TNF) therapy in the past which eventually proved ineffective. The patient was started on Stelara  but this had to be discontinued due to abscess in the ileal region. Stelara was restarted. Despite continued biologic use the patient has severe ongoing disease in the neo-terminal ileum as seen on colonoscopy and cross-sectional imaging. Clinically, he has persistent watery diarrhea and right lower quadrant (RLQ) pain which is severe.
The patient's provider is recommending Stelara 90 milligrams (mg) every (Q) 4 weeks. This request was denied by the plan as this requested dose exceeds the Food and Drug Administration (FDA) approved dose. The subject under review is whether the requested dose would be more beneficial for this patient.

The health plan's determination is overturned.

The request to increase dosing of Stelara to every 4 weeks is likely to be more beneficial for this patient's condition. The patient has already tried and failed anti-TNF biologics. 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 (Stelara) at approved doses.
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 Crohn's Disease (CD), they found serum concentrations of ustekinumab to be proportional to dose and associate with treatment efficacy. Trough concentrations of ustekinumab up to 1.4 micrograms per milliliter (g/mL) 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 milligrams (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; probability [P] = .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; P = .04). Based on the above data Stelara at Q 4 week dosing is appropriate for this patient due to ongoing active disease.