Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease. 
Treatment: Stelara SQ (subcutaneously) 90mg (milligrams) every 4 weeks. 

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

The patient is an adult female with fistulizing Crohn's status post resection. She also has sacroiliitis and erythema nodosum. The patient has failed Entyvio, Humira and Cimzia, and started Stelara 90 milligrams every eight weeks 5 years ago. She initially responded, but recently has lost response with active fistula and sacroiliitis. The physician (AP) is requesting to increase Stelara to 90 milligrams every four weeks. 

The proposed treatment 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 percent (%)) 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 clinical response after dose escalation (two [18%] were primary non-responders to induction while nine [82%] had 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. The most common escalated maintenance dosing was 90 milligrams subcutaneously (SC) every four or six weeks. Clinical response was regained in 52.9% (9/17) of patients who had dose escalation, and 57.1% (4/7) of patients who had combined reinduction and dose escalation (Ma et al., 2017). 

Per Ollech et al. (2020), "We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 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 >4, 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 8 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." 

Medical literature supports dose intensification prior to changing to another agent when there has been some response. This patient had lost response to Stelara 90 milligrams every eight (8) weeks. Therefore, the requested Stelara 90 milligrams every four weeks is clinically appropriate, an accepted standard of medical care, and medically necessary.