Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Ulcerative Colitis.
Treatment: Stelara 90mg/ml syringe every 4 weeks.
The insurer denied the Stelara 90mg/ml syringe every 4 weeks.
The denial is overturned.

The patient is a male with ulcerative colitis diagnosed after presenting with bloody diarrhea. He is status post treatment with sulfasalazine and mesalamine products, but continued to have uncontrolled symptoms.  The patient started Humira several years ago.  Humira levels were not detected the following year.  Colonoscopy showed active disease and he was then started on Remicade.  The Remicade level was undetectable with development of antibodies.  The patient then started Stelara.  He received the first dose of Stelara earlier this year, which worked well without GI (gastrointestinal) symptoms.  However, he started to notice worsening symptoms 2-3 weeks prior to upcoming Stelara injections, having loose stools 3-4 times and some abdominal cramping.  The Stelara level was low at 2.5 most recently.

Yes, the health plan should cover the Stelara every 4 weeks.
The patient received the first dose of Stelara earlier this year, which worked well without GI (gastrointestinal) symptoms.  However, he started to notice worsening symptoms 2 to 3 weeks prior to upcoming Stelara injections, having loose stools 3 to 4 times and some abdominal cramping.  The Stelara level most recently was low at 2.5.

At the American College of Gastroenterology (ACG) Scientific Meeting, 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 <= (less than/equal to) 2 points, with no individual subscore > (less than) 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 States 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 ug/g (micrograms per gram) to 157 ug/g (micrograms per gram). Among patients who had an HBI (Harvey Bradshaw Index) > (less than) 4, a level of CRP (C-reactive protein) 5mg/dL (milligrams per deciliter), a level of fecal calprotectin > (less than) 250ug/g (micrograms 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) (< [less than] 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).

Yes, Stelara every 4 weeks is more beneficial.
Dose escalation of therapy by increasing the frequency of administration or by increasing the dose is conducted in clinical practice if a patient exhibits signs of increased disease activity.