Appeal type: Medical necessity
Decision: Overturned

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

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

The patient is a male with moderate to severe Crohn's disease. He has failed steroids and Remicade. He was started on Stelara 90 mg (milligrams) every 8 weeks, with some, but not a complete response, with increased symptoms at 4 weeks. His provider is requesting to increase Stelara to 90 mg (milligrams) every 4 weeks. 

Yes, the requested Stelara every 4 weeks is medically necessary. 

Medical literature supports dose intensification of biologics in patients who lose response to Food and Drug Administration (FDA) approved dosing. Stelara (ustekinumab) 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, every six weeks, or a combination of intravenous (IV) booster and frequency increase to every six weeks or every four weeks). 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). (3) 

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 re-induction 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. 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 re-induction and dose escalation. (4) 

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 every eight weeks to every four weeks, 90 milligrams every eight weeks to every six weeks), clinical improvement was seen in 73% (8/11) of patients. (2) 

A retrospective study was completed to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD (Crohn's disease) who received subcutaneous ustekinumab 90 milligrams every eight weeks at a single center. "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, the median level of CRP (C-reactive protein) decreased from 8 mg/L (milligrams/liter) to 3 mg/L (milligrams/liter), and median level of fecal calprotectin decreased from 378 ug/g (micrograms/grams) to 157 ug/g (micrograms/grams). Among patients who had an HBI (Harvey Bradshaw Index) > [greater than] 4, a level of CRP (C-reactive protein) greater than or equal to 5mg/dL (milligrams/deciliter), a level of fecal calprotectin > [less than] 250 ug/g (micrograms/grams), 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 less than or equal to 4), 22% had a normal level of CRP (C-reactive protein) (< [greater than] 5 milligrams/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 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." (5) 

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 every eight weeks. 

Medical literature supports dose intensification prior to changing to another agent when there has been some response. This patient has had some response, but recurrent symptoms and evidence of ongoing disease on Stelara 90 mg (milligrams) every eight weeks, with loss of response at 4 weeks. Therefore, the requested Stelara 90 milligrams every four weeks is clinically appropriate and accepted standard of medical care, and medically necessary. 

No, as the requested Stelara every 4 weeks is medically necessary,  the health plan did not act reasonably, with sound medical judgment and in the best interest of the patient by denying it.