Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Crohn's Ileocolitis. 
Treatment: Stelara (at a dose of 90 milligrams every 4 weeks). 

The insurer denied: Stelara (at a dose of 90 milligrams every 4 weeks). 
The denial is upheld. 

The patient is an adult female with Crohn's disease requesting Stelara every four weeks. The prior request was denied due to the amount of drug requested being above the quantity limit, being above the FDA (Food Drug Administration) recommended maintenance dose for treatment of Crohn's disease. The appeal letter describes prior treatment with infliximab, Humira. She underwent ileocecal resection over 10 years ago. She was switched from infliximab to adalimumab six years ago. She developed dermatitis. Colonoscopy from two years ago 
showed active ulcers at the anastomotic site and she was started on Stelara. She initially did well but then she developed pain, frequency, and elevated calprotectin eight months ago. She has diarrhea, cramps, and requesting every four-week dosing. 

The health plan should not cover Stelara 90 milligrams every 4 weeks. 

The dose requested is beyond the maximum dose recommended by the FDA (Food Drug Administration) for maintenance therapy of Crohn's disease. The health plan should not cover the proposed treatment. See literature analysis below. 
The requested health service is not more beneficial than any standard treatment for the insured's condition or disease. 
There are standard options remaining including adding an immune suppressant such as azathioprine, Mercaptopurine, methotrexate, to standard dosing of Stelara. Alternatively high dose mesalamine can be added in combination with Stelara/ immune suppressant medication. The scientific literature does not support this approach. 

At this time, there is insufficient high-quality scientific literature to support the safety and effectiveness of every four-week dosing of Stelara. 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. 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 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)>1 after 163weeks 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-IL12/23 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 agents the optimal management of loss of response to UST (Stelara) is not fully established. Shortening the interval of administration and also re-induction with UST 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 dosing are still scarce." 
Further study is needed to assess the safety and efficacy of dose escalation with Stelara.