Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis Crohn's Disease
Treatment: Stelara 90 mg/mL Syringe, 90 mg every 6 weeks
The insurer denied the Stelara 90 mg/mL Syringe, 90 mg every 6 weeks.
The determination is overturned.

The patient was diagnosed with Crohn's disease [CD]. He has been treated with Azathioprine, and Humira. He had a colonoscopy revealing severe, active ileitis. He was started on Stelara. He had been doing well on Stelara, however, he recently suffered a relapse with increased frequency of loose stools especially prior to his next dosage. His hemoglobin is 13.7, C-reactive protein (CRP) 2, Ferritin 26, white blood cell (WBC) count 7.4, creatinine 1.0, alkaline phosphatase 72, total bilirubin 0.5, aspartate aminotransferase (AST) 27, alanine aminotransferase (ALT) 28. His ustekinumab serum level was 2.5. A dosage escalation of Stelara to 90 mg every 6 weeks has been requested and at issue is whether this is likely to be more beneficial than any standard treatment(s).

The dosage escalation of Ustekinumab [Stelara] to 90 mg every 6 weeks is likely to be more beneficial than any standard treatment. The patient has been suffering from a relapse of his Crohn's disease with an increasing frequency of bowel movements. Additionally, his serum level of Ustekinumab was subtherapeutic at 2.5. The dosage escalation is considered to be the medical standard of care and is supported by current peer-reviewed medical literature.
"We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. 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. Following dose interval shortening, the patients' median Harvey-Bradshaw index (HBI) decreased from 4.5 to 3 (probability [P] = .002), the median level of CRP decreased from 8 milligrams per liter (mg/L) to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 micrograms per gram (g/g) to 157 g/g (P = .57). Among patients who had an HBI greater than (>) 4, a level of CRP greater than or equal to (>=) 5 milligrams per deciliter (mg/dL), 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." [1].
"Our results support ustekinumab (UST) every (Q) 4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy." [2]
"Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing." [3]
"Ustekinumab is approved in CD for a weight-based intravenous (IV) induction dose followed by every 8 weeks of subcutaneous dosing. Response rates by 6 weeks range from 34% (anti- tumor necrosis factor (TNF) failures) to 56% in bio-naive patients. The remainder includes patients who partially-respond (PR) or do not respond (NR). Response by week 16 is 55% (anti-TNF failures) and 73% in bio-naive patients suggestive of a 'delayed response' in some. Experience with anti-TNF drugs demonstrates that a subset of patients respond to dose escalation, which prompts the notion of a potential delayed response phenomenon with Ustekinumab. " [4]
"A majority of patients with moderate to severe CD benefited from UST dose escalation suggesting the clinical utility of optimizing dosing in the treatment course. Response to UST induction dose may be a strong predictor of subsequent response to UST dose escalation." [5]
"Ustekinumab therapy was effective in patients with CD who had not responded to or were intolerant to treatment with a TNF antagonist. Maintenance trough concentrations of ustekinumab above 4.5 g/mL at 26 weeks or later were associated with biomarker reduction and endoscopic response." [6]