Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Digestive System/Gastrointestinal. 
Treatment: Pharmacy/Prescription Drugs. 
The insurer denied Stelara 90mg every 6 weeks. 
The denial is overturned.

This female patient has severe Crohn's colitis. She had previously tried and failed steroids and 5-aminosalicylic acid (5-ASA) agents. She was started on Stelara at standard dosing every 8 weeks but later lost response. She had symptoms of a flare of her Crohn's disease and had elevated inflammatory markers. She had a sub-therapeutic Stelara (ustekinumab) level on therapeutic drug monitoring. Therefore, the attending provider is recommending an escalated dose of Stelara 90 milligrams (mg) every 6 weeks to treat this patient's Crohn's disease.
At issue is whether the proposed health treatment Stelara 90mg every 6 weeks is likely to be more beneficial than any standard treatment for the patient's disease.

The health plan's determination regarding the proposed health service or treatment is overturned in whole.

The proposed health service or treatment Stelara 90mg every 6 weeks is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.
Since this patient was not responding to the standard dosing of Stelara, it is reasonable to increase the dose of Stelara to 90mg every 42 days (6 weeks). Dose escalation in biologic therapy used in inflammatory bowel disease can be done either based on clinical symptoms or laboratory markers or endoscopic or radiological features with or without therapeutic drug monitoring. Dose escalation is done either by increasing the dose of the medication or shortening the interval between doses or sometimes a combination of both. This patient has medically refractory Crohn's disease and has failed every other United States Food and Drug Administration (FDA) approved biological agent used to treat Crohn's disease. There are only a finite number of biological agents used to treat inflammatory bowel disease and the standard of care is to optimize the dose of the biological agent before switching to another agent. 
Crohn's disease results from a pathological immune response to luminal antigens in genetically predisposed individuals. Since the causes of Crohn's disease are complex and only partially understood, treatment is based on the empiric use of anti-inflammatory drugs. Although multiple therapies for Crohn's disease currently exist, a substantial proportion of patients are unresponsive to conventional agents. Ustekinumab offers a treatment option to Crohn's disease patients who have never responded to infliximab, primary non-responders, as well as patients who have attenuated anti-TNF response or become intolerant to anti-TNF therapy.  In a study by Kopylov and colleagues 38 patients (18 males, median age 35.5 years) with Crohn's disease resistant to anti-TNF agents at 3, 6, 12 months and at last follow up were enrolled. There was a need for dose escalation in 47.7% and this was successful in a majority (61.1%) of them. This would suggest that further dose optimization of ustekinumab may be needed in Crohn's disease. Similarly, Ollech and colleagues showed that shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with Crohn's disease (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. Meserve and colleagues showed that in real world settings, ustekinumab dose escalation was effective in achieving response in patients with Crohn's disease with inadequate response, or loss of response to standard dose induction and/or maintenance therapy.
Therefore, the proposed health service or treatment Stelara 90mg every 6 weeks is likely to be more beneficial than any standard treatment or treatments.