Therapeutic Drug Monitoring: Ustekinumab (Stelara)

The ability to measure drug levels has changed how we think about refractory medical disease, particularly in patients with inflammatory bowel disease.  Prior to the availability of therapeutic drug monitoring (TDM), in some situations poor response to therapy could be ascribed to variability in host immune response. Now, it is clear that many cases of refractory medical disease are due to insufficient drug level.  TDM allows for dose individualization to target the right amount of medication.

TDM has an accepted role in anti-TNF therapy.  Now, a study (R Battat et al. Clin Gastroenterol Hepatol 2017; 15: 1427-34) extends the concept of TDM to ustekinumab.  This study which took place between 2014-2015 examined ustekinumab use in 62 patients with refractory Crohn’s disease (CD).  Ustekinumab dosing: 90 mg SC at weeks 0, 1, and 2 for induction, then 90 mg every 4 or 8 weeks for maintenance.

Key findings:

  • At week 26, 80.7% of patients had a clinical response, 66.1% had a clinical remission, and 58.9% had an endoscopic response.
  • In those with an endoscopic response, the mean trough concentration of ustekinumab was 4.7 mcg/mL compared with 3.8 mcg/mL those without an endoscopic response.
  • Using a trough threshold of 4.5 mcg/mL at week ≥26, 75.9% had an endoscopic response whereas those with a level below this trough had a 40.7% endoscopic response
  • The authors did not detect antibodies to ustekinumab in any patient. The authors note that ustekinumab has low immunogenicity and prior UNITI studies indicated antibody formation in 0.2% after induction and 2.3% at 1 year.
  • Unlike combination therapy with anti-TNF therapy, “concurrent immunosuppressive therapy does not explain low immunogenicity, as only 25.8% of patients received these and had neither improved clinical outcomes nor higher drug concentrations.”

Thus far, no clinical studies have demonstrated improved clinical outcomes with dose escalation in the setting of low ustekinumab levels.  A prospective trial would be helpful.

My take: This study shows promising results for ustekinumab for refractory CD.  The low immunogenicity indicates that monotherapy is likely appropriate.  A target level of >4.5 mcg/mL indicates a higher likelihood of response.

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