Diagnosis: Chron's disease
Issue under review: Stelara (Ustekinumab) dosed every four weeks
The insurer denied the Stelara (Ustekinumab) dosed every four weeks.
The denial is overturned.

The patient is a male with Crohn's disease (CD). He has tried and failed treatment with Pentasa, Humira, Remicade and Entyvio. He was started on Stelara 90 mg every eight weeks. He had done well, but he lost response, with active disease on colonoscopy, and an elevated fecal calprotectin and elevated CRP (C-reactive protein). His MD is requesting to increase Stelara to 90 mg every four weeks.

Yes, the treatment with Stelara (Ustekinumab) dosed every four weeks is medically necessary.

The patient has Crohn's disease and has been treated with Stelara 90 mg every eight weeks and has lost response. Medical literature supports dose intensification of biologics in patients who lose response to FDA-approved dosing. Stelara has been found to be safe and effective at doses as high as 90 mg every four weeks.
Results from a retrospective cohort study of patients with CD reported that among 122 patients on ustekinumab, 21 (17%) patients on every eight week maintenance dosing required dose intensification (frequency increased to every four weeks [n=11], every six weeks [n=5], or a combination of IV booster and frequency increase to every six weeks or every four weeks [n=5]). A total of 11 patients (52%) had clinical response after dose escalation (two [18%] were primary nonresponders to induction while nine [82%] had poor initial clinical response).

A multicenter, retrospective, open-label cohort study of adults with moderate to severe CD was conducted to evaluate the long-term maintenance efficacy of ustekinumab therapy. During the maintenance therapy, dose escalation was required in 16.3% (17/104) patients and a combination strategy of reinduction and dose escalation was required in 6.7% (7/104) of patients. The most common escalated maintenance dosing was 90 mg SC every four or six weeks. Clinical response was regained in 52.9% (9/17) of patients who had dose escalation, and 57.1% (4/7) of patients who had combined reinduction and dose escalation. Results from a retrospective, multicenter, open-label study of patients with refractory CD receiving ustekinumab, demonstrated that, among 11 patients who required a dosing interval reduction (includes 90 mg SC every eight weeks to every four weeks [n=8], 90 mg SC every eight weeks to every six weeks [n=1]), clinical improvement was seen in 73% (8/11) of patients.

Results from a retrospective, open-label, observational study of ustekinumab for the treatment of anti-tumor necrosis factor (anti-TNF) resistant CD patients, demonstrated that, among patients who achieved clinical response at the last follow up, dose escalation was required in 35% (7/20)
of patients who received ustekinumab 90 mg SC every eight weeks.

Therefore, the proposed Stelara 90 mg every four weeks is medically necessary, and the health plan did not act reasonably, with sound medical judgment and in the best interest of the patient by denying it.