Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease (CD)
Treatment: Stelara 90 MG/ML (milligrams/milliliter every 4 weeks).

The health plan denied the requested medication as not medically necessary. 
The health plan's determination is overturned.

The patient is a female under management for stricturing Crohn's Disease (CD). The patient was admitted for a small bowel perforation and required a small bowel resection. She has perianal disease with a seton in place. She has an episodically active recto-vaginal fistula. The patient has previously tried and failed Infliximab, Adalimumab, and Azathioprine. The patient had an initially good response on Ustekinumab (Stelara) at conventional dosing of every 8 weeks. However, over time she is developing breakthrough symptoms in the interval between doses. On a recent colonoscopy there is evidence of active disease with stricturing in the terminal ileum. The patient's provider has requested approval for Stelara at 90 mg (milligrams) every 4 weeks.
At issue is the medical necessity of the requested medication Stelara 90 MG/ML (milligrams/milliliter) every 4 weeks.

I recommend overturning, in whole the health plan's determination of medical necessity.

Yes. The request to increase dosing of Stelara to every 4 weeks is medically necessary and is cost-effective and evidence-based. The patient has already tried and failed several other biologics and immune modulators for the treatment of Crohn's disease. She is young and is quickly running out of treatment options. The only remaining drug she has not tried is Vedolizumab however this drug performs poorly in patients with prior anti-tumor necrosis factor (TNF) failure (as in this case).
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 associate with treatment efficacy. Trough concentrations of Ustekinumab up to 1.4 micrograms/liter 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 micrograms/liter) than without (3.8 micrograms/liter ; P (significance of results) = .03). An optimal Ustekinumab threshold trough concentration at week 26 or later was found to be 4.5 micrograms/liter  (area under the curve, 0.67). A greater proportion of patients with trough concentrations of Ustekinumab above 4.5 micrograms/liter  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 micrograms/liter  at week 26 or later also had a lower mean level of C-reactive protein (CRP) (12.6 mg/L (milligrams/liter)) than did patients with trough concentrations below this level (mean level of CRP, 23.9 mg/L; P = .04). This patient's trough Ustekinumab level was well below 4.5 micrograms/liter and therefore increasing the dose to every 4 weeks would be likely to get her to that critical threshold and therefore provide an increased probability of clinical benefit.