Appeal type: Experimental/Investigational
Decision: Overturned

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

The patient is a male with Crohn's disease. The request is for Stelara every four weeks. The prior denial was due to the quantity requested being beyond the maximum FDA (United States Food and Drug Administration) dose recommended for the maintenance therapy of Crohn's disease. In addition the denial described that there was no documentation of failing standard every eight week dosing.

The progress note describes small and large bowel Crohn's disease, resection several years ago, fistula takedown, ileostomy reversal. The Patient was on Remicade, Humira, Stelara, and steroids in the past, incision and drainage of rectal abscess approximately two years ago. The CT (computed tomography) shows active inflammation of the ileum and fistula. Colonoscopy showed ulcers in neoterminal ileum.

The patient was noted to be experiencing diarrhea and pain, and Stelara was increased to every four weeks. He is currently with formed stool, no bleeding, appetite good, iron infusions. He is on no other medicines for Crohn's disease. His hemoglobin is 14.0. His metabolic panel is stable. The request is to continue every four week dosing since the patient has improved.

No, the health plan should not cover the requested Stelara every 4 weeks.
At this time there is insufficient high-quality scientific literature to support the safety and effectiveness of every four-week dosing of Stelara (ustekinumab). There are a lack of randomized controlled studies or well-designed cohort studies that show an improvement in health outcome, safety, and effectiveness with this approach.

The American College of Gastroenterology clinical guideline for the management of Crohn's disease does not recommend every four week dosing of Stelara. This dose requested is beyond the maximum dose recommended by the FDA (United States Food and Drug Administration). It is not recommended in the ACG (American College of Gastroenterology) clinical guideline for the treatment of Crohn's disease.

Haider described dose escalation, but had many limitations to the study: "A significant limitation of this study is the retrospective design. Patients were not randomized, and the decision point to dose escalate to Q4 (every four) week was multifactorial, based on subjective clinical factors, financial variables, and a joint decision between provider and patient. There were no objective criteria for which patients were selected to be dose-escalated, other than PGA (physician global assessment) > [greater than] 1 after 16 [plus/minus] 3weeks of standard dosing. The subjective inclusion criteria of the dose-escalated group potentiates selection bias."

Holvoet did not describe every 4 week dosing: "The recent UNIFI trials show that ustekinumab, an anti-IL [interleukin] 12/23 antagonist, induces clinical remission in moderate-to-severe colitis more often than placebo (respectively 15% vs 5%). Despite the rapid onset of remission, no trials are specifically investigating the use of ustekinumab in Acute Severe Ulcerative Colitis."

Guttierez calling for more study: "Unlike with anti-TNF [tumor necrosis factor] agents the optimal management of loss of response to UST (ustekinumab) is not fully established. Shortening the interval of administration and also re-induction with UST [ustekinumab] have been described in patients after an initial inadequate response or secondary loss of response with good results.  However, data about the efficacy of both strategies in patients failing q8w [every eight weeks] dosing are still scarce."

Sandborn did not study every 4 week dosing; "In Phase 3 studies of ustekinumab, a fully human monoclonal IL [interleukin]-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI (TNF [tumor necrosis factor]-antagonist failures) maintenance are reported. A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg [milligrams] every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg [milligrams] every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment."

Sands did not study every 4 week dosing: "Patients with moderately-to-severely active CD [Crohn's disease] and inadequate response or intolerance to tumor necrosis factor antagonists (UNITI1), or conventional therapy (UNITI-2) were randomized to placebo, ustekinumab 130 mg [milligrams], or 6 mg/kg [milligrams/kilogram] intravenous induction therapy. At Week 8, ustekinumab-treated responders (CDAI [Crohn's disease activity index] reduction 100 or CDAI [Crohn's disease activity index] < [less than] 150 points) were re-randomized to subcutaneous maintenance therapy (IM-UNITI) with placebo, ustekinumab 90mg [milligrams] q12w (every 12 weeks), or q8w (every eight weeks) for 44 additional weeks.  Ustekinumab improved HRQOL [health-related quality of life] in patients with moderately-to-severely active CD [Crohn's disease]."

Therefore, given the above, further study is needed to assess the safety and efficacy of dose escalation with Stelara. As such, the health plan should not cover the requested Stelara every 4 weeks.


No, the requested Stelara every 4 weeks is not more beneficial.
Standard options remain in this case including every eight week dosing of Stelara with an immune suppressant such as methotrexate, azathioprine, Mercaptopurine, and/or high dose mesalamine. The every four week dosing is not supported by scientific literature.