Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Ulcerative colitis,
Treatment: Stelara 90mg/ml Every 4 Weeks, Pre-service.
The insurer denied the Stelara 90mg/ml Every 4 Weeks, Pre-service.
The denial is overturned.

The patient is a female with ulcerative colitis.  The patient failed prednisone, mesalamine, Remicade despite 10 mg / kg (milligrams per kilogram) every 4 week dosing.  The patient also failed Entyvio.  The patient is currently on Stelara.  However, she still has abdominal pain, blood in the stool, nausea / vomiting.  Stelara was increased from every 8 weeks to every 4 weeks.

Yes, the health plan should cover the treatment with Stelara every four weeks.
The patient is currently on Stelara.  However, she still has abdominal pain, blood in the stool, nausea / vomiting.  Stelara was increased from every 8 weeks to every 4 weeks.

In a case series 4 adolescent patients with Crohn disease aged 12, 13, 16, and 17 years received ustekinumab. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations (Bishop C, J Pediatr Gastroenterol Nutr). In a case report by Bertrand V et al, an adolescent with Crohn's disease that was treated with ustekinumab, was described.

Fusillo and colleagues conducted a single-center, prospective cohort study to determine the response rate to ustekinumab and assess potential differences between responders and non-responders to therapy in refractory pediatric IBD (inflammatory bowel disease).  Investigators enrolled 20 patients younger than 21 years with Crohn's disease or indeterminate colitis receiving ustekinumab therapy at the Children's Hospital of Philadelphia. They included patients with prior anti-TNF (tumor necrosis factor) failure and clinically active disease.  Patients received an intravenous injection at induction and subcutaneous injections every 8 weeks. The primary outcome for the trial was clinical response defined as decrease in pediatric disease index scores. 25 patients achieved clinical response by week 6 (52%), and 20 achieved clinical response by their last follow-up (45%).

Dose escalation of Stelara may be required in some patients. In a retrospective multicenter cohort study was performed on patients with CD (Crohn's disease), dose escalation was required in 17 patients (16.3%); response was recaptured in 9/17 (52.9%) (Ma C et al, Inflamm Bowel Dis.). In another multicenter open-label study, dose escalation was effective in 8 of 11 (73%) patients (Khorrami S et al. Inflamm Bowel Dis.).  In a single center retrospective open-label observational study, dose escalation was required in 47.7% of the patients and was successful in 61.1% of them (Kapylov et al.  J Crohns Colitis.).

In a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, 506 patients with CD (Crohn's disease) who received subcutaneous ustekinumab 90 mg (milligrams) every 8 weeks at a single center was reviewed.  Data from 110 patients who initially received subcutaneous ustekinumab 90 mg (milligrams) every 8 weeks and then had their interval shortened to every 4 weeks was studied.  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 g/g (grams per gram) to 157 g/g (grams per gram). Among patients who had an HBI (Harvey Bradshaw Index) >4, a level of CRP (C-reactive protein) 5mg/dL (milligrams per deciliter), a level of fecal calprotectin >250ug/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) (<5 mg/dL [milligrams per deciliter]), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission (Ollech JE et al, Clin Gastroenterol Hepatol.).

Yes, the treatment with Stelara every 4 weeks is likely to be more beneficial.
De-escalation is not appropriate for this patient, as this could lead to destabilization of disease.   Fully utilizing the benefit of Stelara would be indicated prior to changing to another biologic agent, since there are few biologic agents that may be used in the treatment of inflammatory bowel disease.