Outcomes and adverse events in children and young adults undergoing tacrolimus therapy for steroid-refractory colitis

Inflamm Bowel Dis. 2011 Jan;17(1):22-9. doi: 10.1002/ibd.21418. Epub 2010 Aug 18.

Abstract

Background: Children with severe corticosteroid-resistant ulcerative colitis either need to undergo surgery or be treated with more intensive immunosuppression. Our aim was to characterize the short- and long-term outcomes and adverse events associated with the use of tacrolimus in a steroid-refractory pediatric population.

Methods: We retrospectively reviewed the medical records of 46 children with steroid-refractory colitis treated with tacrolimus at Children's Hospital Boston between 1994 and 2008. Oral tacrolimus was initiated at a dose of 0.1 mg/kg twice a day and titrated to yield trough levels of 10-15 ng/mL for induction, and 5-10 ng/mL once in remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) and other measures of disease activity, adverse events, and long-term outcomes were assessed. Statistical analysis of outcomes was performed using SAS statistical software.

Results: Ninety-three percent of patients were discharged without undergoing surgery. The median length of stay after starting tacrolimus was 10 days (range 4-37 days). The mean PUCAI score was 68 ± 13 prior to initiating tacrolimus, and 27 ± 18 at the time of hospital discharge. The probability of avoiding colectomy after starting tacrolimus was 40% at 26 months. The most common adverse events included hypertension (52%) and tremor (44%). There was one seizure and no deaths.

Conclusions: Tacrolimus is useful as induction therapy in pediatric patients with corticosteroid-refractory colitis and side effects are generally mild and reversible. Despite these findings, many patients develop exacerbations of colitis upon transition to maintenance therapies. The long-term colectomy rate in this challenging population remains ≈60% over time.

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adolescent
  • Adrenal Cortex Hormones / pharmacology*
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / pathology
  • Drug Resistance / drug effects*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Retrospective Studies
  • Tacrolimus / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Acute-Phase Proteins
  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Tacrolimus