Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Ulcerative Colitis. 
Treatment: Stelara 90mg Every 4 Weeks, Pre-service. 

The insurer denied the Stelara 90mg Every 4 Weeks, Pre-service. 
The denial is overturned. 

The patient is a male with ulcerative colitis. He has failed Uceris, Cipro, Prednisone, Remicade, Entyvio Simponi, Methotrexate, Humira, Xeljanz, and 6-MP (mercaptopurine). Stelara was started and the patient experienced partial response with breakthrough symptoms, requiring dose escalation to every 4 weeks in early last year.  He responded well to every 4 weeks dosing and is currently on mesalamine and Stelara 90 mg (milligrams) every 4 weeks. 

Yes, the Stelara every 4 weeks is medically necessary. 

This patient has failed all alternative medications and is stable on the requested dose of Stelara at 90 mg (milligrams) every 4 weeks. 

At the American College of Gastroenterology (ACG) Scientific Meeting 2018, results from the induction phase of the Phase III UNIFI study show that treatment with a single IV (intravenous) dose of Stelara induced clinical remission in a significantly greater proportion of UC (ulcerative colitis) patients at week 8, compared with placebo, at both doses studied. 15.6% of patients receiving 130 mg (milligrams) ustekinumab and 15.5% of patients receiving ~6 mg/kg (milligrams per kilogram) ustekinumab achieved clinical remission, compared with 5.3% of patients receiving placebo). Remission was defined as a Mayo score 2 points, with no individual subscore >1. Major secondary endpoints including the proportion of patients in clinical response, endoscopic healing, as well as improvement in health-related quality of life, were also significantly higher at week 8 among patients receiving Stelara compared with patients receiving placebo. About 50% of study participants are considered biologic refractory, and 17% have a history of inadequate response or intolerance to an anti-TNF (tumor necrosis factor) and/or Entyvio (vedolizumab) (article was later published in the NEJM - Sands BE et al. N Engl J Med). 

Stelara was approved by the European Commission for use in ulcerative colitis and by the FDA (United State Food and Drug Administration). 

Dose escalation of Stelara may be required in some patients. In a retrospective multicenter cohort study was performed on patients with CD (Crohn's disease), dose escalation was required in 17 patients (16.3%); response was recaptured in 9/17 (52.9%) (Ma C et al, Inflamm Bowel Dis.). In another multicenter open-label study, dose escalation was effective in 8 of 11 (73%) patients (Khorrami S et al. Inflamm Bowel Dis.).  In a single center retrospective open-label observational study, dose escalation was required in 47.7% of the patients and was successful in 61.1% of them (Kapylov et al.  J Crohns Colitis.). 

In a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, 506 patients with CD (Crohn's disease) who received subcutaneous ustekinumab 90 mg (milligrams) every 8 weeks at a single center was reviewed.  Data from 110 patients who initially received subcutaneous ustekinumab 90 mg (milligrams) every 8 weeks and then had their interval shortened to every 4 weeks was studied.  Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%). Following dose interval shortening, the patients' median HBI (Harvey Bradshaw Index) decreased from 4.5 to 3, the median level of CRP (C-reactive protein) decreased from 8 mg/L (milligrams per liter) to 3 mg/L (milligrams per liter), and median level of fecal calprotectin decreased from 378 g/g (micrograms per gram) to 157 g/g (micrograms per gram). Among patients who had an HBI (Harvey Bradshaw Index) >4, a level of CRP (C-reactive protein) 5mg/dL (milligrams per deciliter), a level of fecal calprotectin >250g/g (microgram per gram), or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI [Harvey Bradshaw Index] score 4), 22% had a normal level of CRP (C-reactive protein) (<5 mg/dL [milligrams per deciliter]), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission (Ollech JE et al, Clin Gastroenterol Hepatol.). 

Therefore, given the above, the Stelara every 4 weeks is medically necessary. 
The patient would be at risk of complications from ulcerative colitis and has limited options for treatment.