Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis:  Crohn's Disease.
Treatment:  Stelara 90mg every 4 weeks.

The insurer denied the Stelara 90mg every 4 weeks.  The determination is overturned.

This is a patient with ileocolonic Crohn's disease and iron deficiency anemia.  He failed high-dose infliximab with methotrexate, with testing showing a lack of detectable medication.  He has been on Stelara 90 mg every 8 weeks, with subsequent improvement documented on 05/29/20; however, on that date, he had decreased energy and appetite during the week prior to Stelara injections, and occasional right upper/mid-abdominal pain; he was having two bowel movements per day.  He was reported to have an undetectable Stelara level, and lack of anti-Stelara antibodies.  At issue is whether the disease for which treatment is requested is a rare disease, whether there is a standard treatment that is likely to be more beneficial than the proposed treatment, and whether the treatment is likely to benefit the enrollee in the treatment of the enrollee's rare disease, and whether such benefit outweighs the risks of such health service or procedure.

The disease for which treatment is requested does not meet the provided definition of a rare disease, as although it can be disabling, it is not currently and has not been subject to a research study by the NIH Rare Diseases Clinical Research Network and it affects more than 200,000 patients annually in the United States.

There does not exist a standard health service or procedure covered by the health care plan that is more clinically beneficial than the requested health service or treatment.  The request for Stelara 90 mg every 4 weeks is more likely to be beneficial than alternatives.

Guidelines for the treatment of Crohn's disease recommend the use of Stelara [1-4].  Stelara is Food and Drug Administration (FDA)-approved for Crohn's disease.  A large randomized controlled trial demonstrated safety and efficacy for induction and maintenance of remission in patients with moderate-severe Crohn's disease that was resistant to anti- tumor necrosis factor (TNF) therapy, which this patient has failed [1].   Another study showed a 73% response in patients with anti-TNF-resistant Crohn's disease, and 80% of responders maintained remission for 1 year [2].  A significant majority of these patients were able to discontinue steroids.  The mechanism of Stelara (ustekinumab) is entirely different than that of immunosuppressants and anti-TNF medications, which the patient has failed [3].

A recent study demonstrated that a significant majority of patients who have failed an anti-tumor necrosis factor medication achieve and maintain response with Stelara [4].  In this case, the patient has failed immunosuppressants, anti-tumor necrosis factor (TNF) therapy, and Stelara every 8 weeks.  The dose of 90 milligrams (mg) every 4 weeks is supported as effective.  A study showed dosing intensification (90 mg every 4 weeks) was used frequently to address loss of response, and a large proportion of patients were able to maintain response [5-7].  One study showed that dose escalation was required and approximately half of patients, and successful in 61.1% of dose escalation attempts [5].  Another study showed efficacy in 73% of patients in whom it was attempted [7].  Additionally, the American College of Gastroenterology guidelines for the treatment of Crohn's disease state that "Those with continued symptoms shouldhave their medication dose adjusted in order to attempt to optimize therapy" [8].  Furthermore, American Gastroenterological Association guidelines for the treatment of Crohn's disease recommend a dosage increase in the setting of uncontrolled disease, when the drug level is low (as in this case) [9].  Continuation of Stelara dosing every 8 weeks may result in complications such as fistula, stricture, bowel obstruction, flare, hospitalization, need for surgery, or other complications, and limited alternatives after multiple medication failures.

Alternatives recommended by guidelines for the treatment of Crohn's disease include vedolizumab (Entyvio) and other anti-TNF medications such as adalimumab (Humira) [8].  As the patient has responded to Stelara, with recurrence of symptoms limited to the week just before Stelara injections, an increase in Stelara is more likely to be effective than a change to an anti-TNF medication, one of which (infliximab) the patient has already failed at a high dose; similarly, a change to Entyvio may result in complete loss of disease control if Entyvio is ineffective.  For these reasons, Stelara 90 mg every 4 weeks is more likely to be effective then a change to a new alternative.

The use of Stelara 90 mg every 4 weeks is likely to be effective, as the patient has good disease control except in the week prior to injections, at which time the drug has been found to be undetectable-the issue is insufficient drug dosing [9].  A study showed dosing intensification (90 mg every 4 weeks) was used frequently to address loss of response, and a large proportion of patients were able to maintain response [5-7].  One study showed that dose escalation was required and approximately half of patients, and successful in 61.1% of dose escalation attempts [5].  Another study showed efficacy in 73% of patients in whom it was attempted [7].  Additionally, American College of Gastroenterology guidelines for the treatment of Crohn's disease state that "Those with continued symptoms shouldhave their medication dose adjusted in order to attempt to optimize therapy" [8].  Furthermore, the American Gastroenterological Association guidelines for the treatment of Crohn's disease recommend dosage increase in the setting of uncontrolled disease, when the drug level is low (as in this case) [9].  Based on this literature, the potential benefits of Stelara 90 mg every 4 weeks does outweigh the risks.