Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis Ulcerative Colitis.
Treatment Stelara 90 mg every 6 weeks.

The insurer denied the Stelara 90 mg every 6 weeks.  The determination is upheld.

The patient has a history of ulcerative colitis, and psoriasis. He has previously been treated with Imuran, Methotrexate, Remicade, and Entyvio.  He has been receiving Stelara [90 milligrams (mg) every 8 weeks].  He had developed diarrhea, hematochezia, and bloating.  A stool for Clostridum (C) difficile toxin was negative.  A fecal calprotectin level was 578.  Subsequently, his symptoms have abated.  He had been having 2 bowel movements daily without hematochezia, nor abdominal pain.  A dosage escalation of Stelara to 90 mg every 6 weeks has been requested, due to his psoriasis exacerbation and elevated fecal calprotectin.  At issue is whether the Stelara 90mg/ml 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.

There were no specific gastroenterological indications for the dosage escalation of the patient's Stelara from 90 mg every 8 weeks to 90 mg every 6 weeks.  The dosage escalation was requested, due to an exacerbation of the patient's psoriasis and an elevated fecal calprotectin level, although 3 months subsequent to the measurement of the fecal calprotectin, the patient had been clinically improved.  The dosage escalation is not likely to be more beneficial than continuation of the current dosage regimen for treatment of his ulcerative colitis (UC). 

"Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175).  Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis." [1].

"We collected data from 2 phase 3 trials (1 induction and 1 maintenance), in which patients with moderate to severe ulcerative colitis received an intravenous induction dose of ustekinumab (130 mg, number (n) = 320; or approximately 6 milligrams per kilogram (mg/kg), n = 322).  Responders were assigned randomly to groups that received subcutaneous maintenance ustekinumab (90 mg) every 8 weeks (n = 176) or 12 weeks (n = 172), or placebo (n = 175).  We evaluated the association between ustekinumab concentration and efficacy, serum based on clinical effects (Mayo score), histologic features, and inflammation (measurement of C-reactive protein, fecal calprotectin, and fecal lactoferrin), as well as safety (infections, serious infections, and serious adverse events), during induction and maintenance therapy.  Optimal serum concentrations of ustekinumab were identified using receiver operating characteristic curve analyses.

In patients with ulcerative colitis, dose-proportional serum concentrations of ustekinumab, unaffected by prior biologic or concomitant immunomodulator therapy, reached steady state by the second maintenance dose; the median trough concentration for dosing every 8 weeks was approximately 3-fold that of dosing every 12 weeks.  Serum concentrations were associated with clinical and histologic features of efficacy and normalization of inflammation markers.  The week-8 concentration threshold for induction of response was 3.7 micrograms per milliliter [ug/mL].  A steady-state trough serum concentration of 1.3 ug/mL or higher was associated with a higher rate of clinical remission compared with patients who had lower serum concentrations.  Serum concentrations of ustekinumab were not associated with infections, serious infections, or serious adverse events.  In an analysis of data from 2 phase 3 trials of patients with ulcerative colitis, we found that serum concentrations of ustekinumab were proportional to dose, unaffected by prior biologic or concomitant immunomodulator therapies, associated with clinical and histologic efficacy and markers of inflammation, and were not associated with safety events at doses evaluated. Ustekinumab pharmacokinetics are consistent between patients with Crohn's disease versus ulcerative colitis." [2]

"Pts in response 8 weeks after receiving intravenous UST [ustekinumab] were randomized to receive maintenance treatment with subcutaneous (SC) placebo or UST 90 mg every 8 (q8w) or 12 weeks (q12w).  MH was achieved at Week 44 in 24.1%, 38.8%, and 45.9% of pts treated with placebo, UST q12w (probability [P] = 0.002), and UST q8w (P 0.001), respectively." [3]

"The need and effectiveness of ustekinumab optimisation to every 4 weeks dosing will require further study." [4].

"Further studies of large, real-world cohorts are needed to assess the long-term effectiveness and safety of ustekinumab in UC." [5]

The health Plan's determination regarding the dosage escalation of Stelara is upheld in whole.