P0601 THE USE OF TACROLIMUS IN ELEVEN CHILDREN WITH STEROID-DEPENDENT/STEROID-RESISTANT ULCERATIVE COLITIS

Abstract

Introduction: Tacrolimus is a potent macrolide immunosuppressant used widely in liver and small bowel transplant patients. It has been studied in inflammatory bowel disease as an alternative to IV cyclosporin in patients with severe steroid-dependent or steroid-resistant (SD/SR) UC. In this study we examined the efficacy and safety of tacrolimus for induction and maintenance therapy of pediatric SD/SR UC. Methods: This is a retrospective review of 11 patients initially diagnosed with SD/SR UC who were treated with tacrolimus for induction and maintenance of remission. All patients were either steroid-dependent, defined as unable to wean from steroids secondary to diarrhea, bloody stools, or abdominal pain, or steroid-resistant, defined as continued diarrhea or bloody stools despite treatment with IV steroids for at least 4 days. All patients were initially given tacrolimus 0.2 mg/kg/d divided BID with goal trough blood levels between 10 and 15 ng/ml. Remission was defined as HBI <4. All patients were closely monitored for renal toxicity, received PCP prophylaxis, and received oral magnesium supplementation (if necessary). Results: Ten patients responded to therapy within 14 days. Seven of these patients weaned from steroids on average 7.5 weeks from the start of tacrolimus therapy. Four patients achieved prolonged remission and remain in remission on tacrolimus alone (mean follow up 17 months). Five patients achieved remission in two weeks, only to flare either during steroid weaning (3) or following steroid withdrawal (2). Despite maintaining adequate levels of tacrolimus, three patients who responded in the short-term ultimately required colectomy. Two other patients with short-term response to therapy remain symptomatic. One patient achieved remission, but had headaches associated with tacrolimus, and was changed to azathioprine. The last patient had no response to tacrolimus, developed tacrolimus-associated neurotoxicity with seizures, and ultimately required colectomy. One of the patients requiring colectomy developed EBV-associated lymphoproliferative disorder. The main side effect of tacrolimus therapy was neurotoxicity, seen in 3 patients with complaints of seizure (1), tremulousness (3), and headaches (1). No nephrotoxicity or infectious complications were encountered. Conclusion: Prolonged treatment with tacrolimus has significant risks, and should only be attempted by physicians with a strong comfort level with dosing this drug and monitoring for its side effects. This retrospective study indicates that tacrolimus may have a role in pediatric steroid-resistant and steroid-dependent UC for both induction and maintenance of remission.