Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Crohn's Disease
Treatment: Stelara every four weeks
The insurer denied the Stelara every four weeks.
The denial is overturned.

The patient is an adult male with moderate to severe Crohn's disease (CD). He has failed Remicade and started Stelara 90 milligrams (mg) every eight weeks last year. He initially did well, but then had increased symptoms with evidence of active disease, and serum Stelara level was low at 2.2. Stelara was increased to 90 mg every four weeks with good results. On every six weeks, the patient gets increased symptoms at four to six weeks. Fecal calprotectin is elevated at 651. The attending physician is requesting to increase Stelara to 90 mg every four weeks.

The proposed Stelara 90 mg every four weeks is medically necessary.

Results from a retrospective cohort study of patients with 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 CD was conducted to evaluate the long-term maintenance efficacy of ustekinumab therapy. The most common escalated maintenance dosing was 90 mg 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 [C-reactive protein] decreased from 8 mg/L [liter] to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 ug/g [micrograms/gram] to 157 ug/g (P = .57). Among patients who had an HBI > [greater than] 4, a level of CRP greater than or equal to 5 mg/dL [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] 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 some response, but evidence of active disease and low serum Stelara levels on 90 mg every eight weeks. He had ongoing active disease with elevated calprotectin and increased symptoms at four to six weeks on every six weeks dosing. He had done well on 90 mg every four weeks. Therefore, the requested Stelara 90 mg every four weeks is clinically appropriate, an accepted standard of medical care, and medically necessary.