Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Ulcerative Colitis
Treatment: Stelara (every 4 weeks), Pre-service
The insurer denied the Stelara (every 4 weeks), pre-service.
The denial is overturned.

Yes, the health plan should cover the Stelara every 4 weeks.

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% (percent) 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 or equal to 2 points, with no individual sub score > (greater 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) [Sands BE, et al. N Engl J Med].

Stelara was approved by the European Commission for use in UC 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 that 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]. In another multicenter open-label study, dose escalation was effective in 8 of 11 (73%) patients [Khorrami S, et al]. 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].

In a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center was reviewed. Data from 110 patients who initially received subcutaneous ustekinumab 90 mg 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 decreased from 4.5 to 3, the median level of CRP decreased from 8 mg/L (milligrams per liter) to 3 mg/L, and median level of fecal calprotectin decreased from 378 ug/g (micrograms per gram) to 157 ug/g. Among patients who had an HBI > 4, a level of CRP 5mg/dL (milligrams per deciliter), a level of fecal calprotectin > 250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score of 4), 22% had a normal level of CRP (> 5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission [Ollech JE, et al].

Yes, the Stelara every 4 weeks is more beneficial.

Fully utilizing the benefit of Stelara would be indicated prior to changing to another biologic agent, since there are few biologic agents that may be used in the treatment of UC.