Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease. 
Treatment: Stelara 90MG/ML (milligrams per milliliter) SC (subcutaneously) SOSY (Solution Prefilled Syringe) dosed every 4 weeks. 

The insurer denied: Stelara 90MG/ML (milligrams per milliliter) SC (subcutaneously) SOSY (Solution Prefilled Syringe) dosed every 4 weeks. 
The denial is overturned. 

The patient is an adult female with moderate to severe Crohn's disease. She has failed Pentasa, steroids, and Remicade, and started Stelara 90 mg (milligrams) every 8 weeks 2 years ago. She did well until last year, when she was noted to have loss of response. Due to this, Stelara was increased to 90 mg (milligrams) every 6 weeks. She continues to have intermittent episodes of pain and diarrhea. Her 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. 

Medical literature supports dose intensification of biologics in patients who lose response to the Food and Drug Administration (FDA) approved dosing. Stelara has been found to be safe and effective at doses as high as 90 milligrams every four weeks. 

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 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 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). 

A retrospective study was completed to determine the effectiveness of ustekinumab dose interval shortening, from patients with CD (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 [milligrams] every 8 weeks and then had their interval shortened to every 4 weeks. 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 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." 

Lastly, results from a retrospective, open-label, observational study of ustekinumab for the treatment of anti-tumor necrosis factor (TNF) resistant CD (Crohn's disease) patients demonstrated that, among patients who achieved clinical response at the last follow-up, dose escalation was required in 35% (7/20) of patients who received ustekinumab 90 milligrams subcutaneously every eight weeks. 

Therefore, the requested Stelara 90 milligrams every 4 weeks is medically necessary.