Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease
Treatment: Stelara (dosed every 4 weeks)
The insurer denied the Stelara (dosed every 4 weeks).
The denial is overturned.

The patient is a female with moderate to severe Crohn's. She has failed Humira, and started Stelara 90 mg (milligrams) every 8 weeks. She had some response, but recent colonoscopy revealed active ileal ulcerations. Her provider is requesting to increase Stelara to 90 mg every 4 weeks.

Yes, the 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 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% [percent]) 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 clinical response after dose escalation (two [18%] were primary non-responders to induction while nine [82%] had poor initial clinical response).

A multicenter, retrospective, open-label cohort study of adults with moderate to severe CD 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) 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 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.

Results from a retrospective, multicenter, open-label study of patients with refractory CD receiving ustekinumab demonstrated that, among 11 patients who required a dosing interval reduction (includes 90 mg every eight weeks to every four weeks, 90 mg every eight weeks to every six weeks), clinical improvement was seen in 73% (8/11) of patients.

A retrospective study was completed to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every eight weeks at a single center.

Per Ollech, et al, "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 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 per liter] to 3 mg/L [milligrams per liter], and median level of fecal calprotectin decreased from 378 ug/g [micrograms per gram] to 157 ug/g [micrograms per gram]. Among patients who had an HBI (Harvey Bradshaw Index) > [greater than] 4, a level of CRP (C-reactive protein) 5mg/dL (milligrams per deciliter), a level of fecal calprotectin > [greater than] 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 4), 22% had a normal level of CRP (C-reactive protein) (< [less than] 5 mg/dL [milligrams per deciliter]), 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 (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 (anti-TNF) resistant CD 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 mg 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 lost it to Stelara 90 mg every eight weeks, with active disease on colonoscopy. Therefore, the requested Stelara 90 mg every 4 weeks is clinically appropriate, an accepted standard of medical care and medically necessary.

Stelara 90 mg every 4 weeks is medically necessary; the health plan act did not reasonably, with sound medical judgment, or in the best interest of the patient by denying it.