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 upheld.

The patient was diagnosed with ileocolonic Crohn's disease after presenting with weight loss and iron-deficiency anemia.  He had an initially promising response to induction therapy with infliximab, but soon lost responsiveness.  Dose escalation to 10 milligrams per kilogram (mg/kg) every 6 weeks, a maximal dose, resulted in no improvement, with undetectable trough drug levels.  Addition of methotrexate resulted in no improvement.  
Therapy was changed from infliximab to ustekinumab (Stelara) at standard adult dosing of 90 micrograms (mcg) every 8 weeks.  When last seen, he was feeling generally well, having 2 formed stools per day, improved energy, growth, and weight gain.  However, his lab results showed persistent mild anemia with microcytic red blood cell (RBC) indices, low iron (Fe), and low transferrin saturation.  He had been taking 325 milligrams (mg) iron sulfate (FeSO4) once daily (60 milligrams (mg) elemental iron, 1.7 mg/kg/day).  I calculate his Pediatric Crohn's Disease Activity Index to be quite low (5), which indicates clinical remission.

Based on persistent iron deficiency anemia, the request is to double the Stelara dose by decreasing the dose interval from 4 weeks to 8 weeks.  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.

Crohn's disease is not a rare disease by these criteria.

The standard treatment would be iron therapy.  The patient is gaining weight and is essentially asymptomatic.  His recent clinic note indicates that he seems to have somewhat more frequent stools and reduced energy during the week prior to his next scheduled (8-week) Stelara injection, but otherwise he has no other symptoms.  He has demonstrated good weight gain.  He does clearly have a persistent iron deficiency but is currently receiving a very low iron supplement dose.

Although the literature supports dose escalation with Stelara when there is loss of response to the current dose, he does not have symptoms that suggest this.  His C-reactive protein (CRP) is completely normal, and his erythrocyte sedimentation rate (ESR) is only the slightly elevated.  There is not any other documentation of increased intestinal inflammation-- there is no fecal calprotectin or fecal occult blood test, nor is there any new endoscopic evidence of inadequate response to therapy.

Before considering an escalation of the Stelara dosing, treating the iron deficiency more aggressively is warranted and is likely to resolve the anemia directly.  Intravenous iron sucrose, calculated to replace the deficit over several infusions, would be a strong consideration, and would work more quickly than a full therapeutic dose (3-5 mg/kg/day) of oral iron.  Only with a clear tendency for return of gastrointestinal and systemic symptoms in the week before the next Stelara injection, would a trial of reducing the Stelara dose interval be favored.  The dose should be tailored to match the clinical need, reducing the interval by 1-2 weeks to every 6-7 weeks would make more sense than jumping to a 4-week interval.  The dose should not escalate the dose based purely on the trough drug level when symptoms are well-controlled.  If there is any question of relapse, measuring fecal calprotectin would provide good information regarding this, as would a repeat colonoscopy.  The latter would be indicated prior to major dose escalation, especially if the fecal calprotectin is elevated.

Stelara dose escalation has been shown to be beneficial when there is loss of disease control on the current standard dose.  However, there is no indication of a clinical relapse in this case, only the persistence of iron deficiency on a subtherapeutic oral iron dose.