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 denial is upheld.

The patient is a male who has a history of Crohn's disease. As the patient evidenced increasing symptoms while receiving Stelara 90 mg (milligrams) every 8 weeks the provider has now requested the provision of Stelara 90 mg (milligrams) every 4 weeks as maintenance treatment. The provider supplied articles from the medical literature.

No, the health plan should not cover the Stelara every 4 weeks.
There is insufficient medical literature to show that dosing every 4 weeks has a positive effect on healthcare outcomes more than standard treatments.

A review of the literature indicates that there have been no significant studies to date demonstrating the safety and efficacy of Stelara dose escalation to every 4 weeks in Crohn's disease other than anecdotal reports, e.g. as follows:

Per Greenup A. et al, in the absence of therapeutic drug monitoring, empirical dose escalation has been considered as a strategy to optimize response in patients with either primary or secondary non-response. Efficacy and safety of UST (ustekinumab) 90mg (milligrams) subcutaneous (SC) every 4 weeks is not known.

A retrospective, observational study of compassionate use of UST (ustekinumab) in CD (Crohn's disease) was conducted at a Canadian tertiary center. Results indicate that real-life experience of UST (ustekinumab) use in patients with CD (Crohn's disease), maintenance dose escalation to 90mg (milligrams) every 4 weeks had a modest benefit in achieving a clinical response. This may be suggestive of the mechanism of loss of response to UST (ustekinumab) being driven by factors other than low bioavailability due to processes such as rapid clearance. Further assessment in larger cohorts as well as the use of therapeutic drug monitoring will be important to evaluate the usefulness of dose escalation for patients on UST (ustekinumab).

Reports such as the above are anecdotal and involve small numbers of patients. Therefore the usefulness, efficacy and safety of dose escalation of Stelara in patients with refractory Crohn's disease requires further study and would not be considered medically appropriate.

Despite the patient's presentation and history, there is no cogent medical literature or society guidelines to recommend dosing Stelara at an interval of every 4 weeks for maintenance. There is no medical literature to show that this dosing frequency has a positive effect on healthcare outcomes. The formulary medications, including Stelara at a dosing of every 8 weeks for maintenance, is as effective and without more adverse side effects than the requested 4-week dosing schedule.

The article as supplied by Ollech et al. concluded, "Shortening the ustekinumab 90 mg [milligrams] dose interval to 4 weeks for patients with CD [Crohn's disease] 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." The article therefore only asserts that patients "might benefit" from this approach.

No, the requested Stelara every 4 weeks is not more beneficial.
There is insufficient cogent medical literature to support the dosing of Stelara at a frequency of every 4 weeks as opposed to standard therapy. There is insufficient medical literature to show that dosing every 4 weeks has a positive effect on healthcare outcomes more than standard treatments.

Reports with respect to Stelara every 4 weeks are anecdotal and involve small numbers of patients. Therefore the usefulness, efficacy and safety of dose escalation of Stelara in patients with refractory Crohn's disease requires further study and would not be considered medically appropriate.

Jauregui-Amezaga et. al., Danese, and Simon, et. al. all note the use of Stelara in the management of Crohn's; however, there is no notation or support of use every 4 weeks for maintenance dosing.