Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease
Treatment: Stelara 90 mg/ml (milligrams per milliliter) syringe every 4 weeks
The insurer denied the Stelara 90 mg/ml syringe every 4 weeks.
The denial is overturned.

The patient is a female with moderate to severe Crohn's disease (CD). She has failed Pentasa and Remicade. She started Stelara 90 mg (milligrams) every 8 weeks approximately two years ago. She had some, but not a complete response, with improvement in abdominal pain, but increased diarrhea and joint pains. Stelara was increased to 90 mg every 4 weeks with improvement in abdominal pain and diarrhea. Her provider is requesting to continue Stelara at 90 mg 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 mg every 4 weeks.

Results from a retrospective cohort study of patients with CD reported that among 122 patients on ustekinumab, 21 (17% [percent]) patients on every 8 week maintenance dosing required dose intensification (frequency increased to every 4 weeks, every 6 weeks, or a combination of intravenous (IV) booster and frequency increase to every 6 weeks or every 4 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). [3]

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) 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 mg subcutaneously (SC) every 4 or 6 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. [4]

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 8 weeks to every 4 weeks, 90 mg every 8 weeks to every 6 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 who received SC ustekinumab 90 mg every 8 weeks at a single center. "We obtained data from 110 patients who initially received SC 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 decreased from 4.5 to 3, the median level of CRP decreased from 8 mg/L [milligrams/liter] to 3 mg/L, and median level of fecal calprotectin decreased from 378 ug/g [micrograms/gram] to 157 ug/g. Among patients who had an HBI (>) greater than 4, a level of CRP greater than or equal to 5 mg/dL [milligrams/deciliter], 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 (less than or equal to 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." [5]

Lastly, results from a retrospective, open-label, observational study of ustekinumab for the treatment of anti-tumor necrosis factor (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 8 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 ongoing symptoms on Stelara 90 mg every 8 weeks and is doing well on Stelara 90 mg every 4 weeks. Therefore, the requested Stelara 90 mg every 4 weeks is clinically appropriate, an accepted standard of medical care, and medically necessary.

As the requested dose of Stelara is medically necessary, the health plan did not act reasonably, with sound medical judgment, or in the best interest of the patient by denying it.