Outcomes and adverse events in children and young adults undergoing tacrolimus therapy for steroid-refractory colitis.
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.
Watson
Sheree
S
Division of Gastroenterology, Children's Hospital, Boston Massachusetts, USA.
Pensabene
Licia
L
Mitchell
Paul
P
Bousvaros
Athos
A
D000209:Acute-Phase Proteins / Q000378:metabolism; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004351:Drug Resistance / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000209:Acute-Phase Proteins; D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016559:Tacrolimus