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. 

The patient is an adult female with moderate to severe ulcerative colitis. After failing conventional therapy, she started Stelara 90 milligrams every eight weeks, and had some, but not a complete response, with urgency, bleeding and active disease on recent colonoscopy. The attending physician is requesting to increase Stelara to 90 milligrams every four weeks. 

Stelara 90 milligrams every four weeks should be covered by the health plan. 
Medical literature supports dose intensification of biologics in patients who lose response to Food and Drug Administration (FDA) approved dosing. Studies pertaining to dose intensification have been performed in patients with Crohn's disease. Dose intensification of Stelara in ulcerative colitis is widely used and accepted by gastroenterologists. 

Results from a retrospective cohort study of patients with Crohn's disease (CD) reported that among 122 patients on ustekinumab, 21 (17%) patients on every eight-week maintenance dosing required dose intensification (frequency increased to every four weeks [n=11], every six weeks [n=5], or a combination of intravenous (IV) booster and frequency increase to every six weeks or every four weeks [n=5]).  A total of 11 patients (52%) had a clinical response after dose escalation (two [18%] were primary non-responders to induction while nine [82%] had a poor initial clinical response) (Young et al., 2018). 

A multicenter, retrospective, open-label cohort study of adults with moderate to severe Crohn's disease was conducted to evaluate the long-term maintenance efficacy of ustekinumab therapy. During the maintenance therapy, dose escalation was required in 16.3% (17/104) of patients and a combination strategy of reinduction and dose escalation was required in 6.7% (7/104) of patients. The most common escalated maintenance dosing was 90 milligrams subcutaneously (SC) every four or six weeks (Ma et al., 2017). 

A retrospective study was completed to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with Crohn's disease who received subcutaneous ustekinumab 90 milligrams every eight weeks at a single center. Per Ollech et al. (2020), "We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every eight weeks and then had their interval shortened to every four weeks. 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 (8) patients (7%). Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 ug/g to 157 ug/g (P = .57). Among patients who had an HBI (Harvey Bradshaw Index) greater than four, a level of CRP greater than or equal to 5 mg/dL, a level of fecal calprotectin >250 ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score less than or equal to 4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission.  Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every eight weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe." 

The requested Stelara 90 milligrams every four weeks is medically necessary and should be covered by the health plan.