Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Ulcerative Colitis. 
Treatment: Stelara 90MG (milligrams) every 4 weeks. 

The insurer denied: Stelara 90MG (milligrams) every 4 weeks. 
The denial is overturned. 

This patient is an adult female with ulcerative colitis who failed Entyvio and is on Stelara every eight weeks.  She has urgency and rectal bleeding.  Her colonoscopy showed active colitis. 

The health plan should cover the requested health service. 

In a study by Sands BE et al., ustekinumab as eight-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis, was studied. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 milligrams [320 patients] or a weight-range-based dose that approximated six milligrams per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy eight weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 milligrams of ustekinumab (either every 12 weeks [172 patients] or every eight weeks [176]) or placebo (175).  The percentage of patients who had clinical remission at week eight among patients who received intravenous ustekinumab at a dose of 130 milligrams (15.6%) or six milligrams per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 milligrams of subcutaneous ustekinumab every 12 weeks (38.4%) or every eight weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively) (1). 

In a maintenance study by Panaccione R, et al, among all patients randomized in maintenance, symptomatic remission rates (stool frequency=0/1; rectal bleeding=0) at Week 92 were, 64.5% and 67.6% in the ustekinumab every 12 weeks and every eight weeks groups, respectively. Among randomized patients treated in the long-term extension, 78.7% and 83.2% of patients receiving every 12 weeks and every eight weeks, respectively, attained symptomatic remission at Week 92; greater than 95% of patients in symptomatic remission at Week 92 were corticosteroid-free (3). 

In a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, 506 patients with Crohn's disease who received subcutaneous ustekinumab 90 milligrams every eight weeks at a single center was reviewed.  Data from 110 patients who initially received subcutaneous ustekinumab 90 milligrams every eight weeks and then had their interval shortened to every four 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 eight patients (7%). Following dose interval shortening, the patients' median Harvey Bradshaw Index decreased from 4.5 to 3.0 (P = .002), the median level of C-reactive protein decreased from 8.0 milligrams per liter to 3.0 milligrams per liter (P = .031), and median level of fecal calprotectin decreased from 378 grams per gram to 157 grams per gram (P = .57). Among patients who had an Harvey Bradshaw Index greater than four, a level of C-reactive protein five milligrams per deciliter, a level of fecal calprotectin greater than 250 micrograms per gram, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (a Harvey Bradshaw Index score of four), 22% had a normal level of C-reactive protein (less than five milligrams per deciliter), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission (7).