Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Digestive System/Gastrointestinal/Crohn's Disease.
Treatment: Pharmacy/Prescription Drugs/Stelara.
The health plan denied the requested medication, Stelara, as experimental/investigational. 
The health plan's determination is overturned.

This is a review of the use of Stelara (ustekinumab) to treat severe Crohn's disease (CD) in a patient. This female patient has severe ileocolonic Crohn's disease. She has previously tried and failed two anti-tumor necrosis factor (TNF) agents (infliximab and adalimumab). She was started on Stelara. She was initially doing well on Stelara at standard dosing every 8 weeks, but lost response recently, as manifested with a flare of her Crohn's disease. She had elevated inflammatory markers (fecal calprotectin). Therefore, the attending gastroenterologist is requesting an escalated dose of Stelara 90 milligrams (mg) SC (subcutaneous) every 4 weeks to treat this patient's severe Crohn's disease.

Based on the clinical data provided, I overturn, in whole the health plan's determination regarding the proposed health service or treatment.

Yes, the proposed health service or treatment Stelara every 4 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 standard dosing of Stelara, it is reasonable to increase the dose of Stelara to 90 mg every 4 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. 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. Therefore, it is medically necessary to use Stelara 90 mg SC every 4 weeks to treat this patient's severe Crohn's disease.
While therapeutic levels of infliximab and adalimumab are well established in the medical literature, there is less data on appropriate therapeutic levels of ustekinumab since this medication and therapeutic drug monitoring of ustekinumab have been available for only a few years as opposed to over a decade for the anti-tumor necrosis factor (TNF) agents. Current guidelines for therapeutic drug monitoring for patients with inflammatory bowel disease (IBD) address only the anti-TNF agents and not vedolizumab or ustekinumab. The current evidence supporting the role of therapeutic drug monitoring (TDM) regarding ustekinumab is based on two exposure-response relationship studies showing that higher ustekinumab concentrations correlate to better therapeutic outcomes. At this time, there are still no studies comparing either proactive or reactive TDM with empiric ustekinumab optimization. Therefore, although there are emerging data that may show an association between drug concentrations and outcomes, they are not sufficient to guide specific induction and maintenance drug concentrations for vedolizumab and ustekinumab other than confirming that there is a detectable drug.

The use of Stelara 90mg SC every 4 weeks to treat this patient's Crohn's disease is medically necessary.