Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Ulcerative colitis.
Treatment: Stelara 90 MG/ML SC (subcutaneously) SOSY (prefilled syringe) dosed monthly.

The insurer denied Stelara 90 MG/ML SC (subcutaneously) SOSY (prefilled syringe) dosed monthly.  The denial is overturned.

The patient is an adult male with moderate to severe ulcerative colitis. He has failed Humira and Remicade. He was started on Stelara last year. He has had some, but not a complete response. His provider is requesting to increase Stelara to 90 mg (milligrams) every 4 weeks. 

The requested Stelara 90 mg (milligrams) every 4 weeks is medically necessary.
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 CD (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).

Results from a retrospective, multicenter, open-label study of patients with refractory CD (Crohn's disease) receiving ustekinumab demonstrated that, among 11 patients who required a dosing interval reduction (includes 90 milligrams subcutaneously every eight weeks to every four weeks [n=8], 90 milligrams subcutaneously every eight weeks to every six weeks [n=1]), clinical improvement was seen in 73% (8/11) of patients (Khorrami et al., 2016).

Per Ollech et al. (2020), "We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg (milligrams) every 8 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 [Harvey Bradshaw Index] decreased from 4.5 to 3 (P = .002), the median level of CRP [C-reactive protein] decreased from 8 mg/L [milligrams per liter] to 3 mg/L [milligrams per liter] (P = .031), and median level of fecal calprotectin decreased from 378 ug/g [micrograms per gram] to 157 ug/g [micrograms per gram] (P = .57). Among patients who had an HBI [Harvey Bradshaw Index] >4, a level of CRP [C-reactive protein] greater than or equal to 5 mg/dL [milligrams per deciliter], a level of fecal calprotectin >250 ug/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 less than or equal to 4), 22% had a normal level of CRP [C-reactive protein] (<5 milligrams per deciliter), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. Shortening the ustekinumab 90 mg (milligrams) dose interval to 4 weeks for patients with CD (Crohn's disease) 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" (Ollech et al., 2020). 

Therefore the requested Stelara 90 milligrams every four weeks is medically necessary.