title: Thalidomide use and outcomes in pediatric patients with Crohn disease refractory to infliximab and adalimumab.
abstract: OBJECTIVE
  The aim of the study was to evaluate thalidomide as rescue therapy for pediatric patients with severe refractory Crohn disease (CD) who failed to respond to antitumor necrosis factor (TNF) biologic agents.
  
  
  METHODS
  A computerized database was used to identify children with CD who had failed conventional immunosuppression therapy and received thalidomide rescue therapy. Twelve patients, mean age at diagnosis 10 years, were identified. Eight children had disease localized to the ileum and colon and 4 to the gastroduodenal area and colon. Five cases were complicated by strictures and 7 by fistulae. Previous drug therapy included azathioprine/6-mercaptopurine (11/12), methotrexate (7/12), and anti-TNF biologics (12/12). Outcome measures were Harvey-Bradshaw Index, change in prednisone dose, hospitalizations, bowel resections, and incision and drainage procedures. Laboratory evaluations were calculated before and after 1 to 6 months of thalidomide.
  
  
  RESULTS
  Mean Harvey-Bradshaw Index score improved from 11.8 to 3.9 (P = 0.0004), mean prednisone dose decreased from 13.9 to 2.3  mg/day (P = 0.001), mean number of hospitalizations decreased from 6.3 to 1.3 (P = 0.002), and erythrocyte sedimentation rate decreased from 35 to 14  mm/h (P = 0.02). The surgery rate pre-thalidomide was 0.031 and on thalidomide was 0.004. Of the 7 patients with fistulae, 5 had complete fistula closure, 1 had partial closure, and 1 showed no improvement. Adverse reactions that resulted in discontinuation of thalidomide are as follows: 42% peripheral neuropathy, 17% worsening of the CD, 8% dizziness, and 8% allergic reaction. All 5 patients who developed peripheral neuropathy had clinical resolution of the neurologic symptoms within 2 to 3 months after stopping thalidomide.
  
  
  CONCLUSIONS
  Thalidomide is a potentially effective rescue therapy for severe refractory CD in children who fail to respond to anti-TNF medications.
authors.affiliation: Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, IL, USA. lfelipez@peds.bsd.uchicago.edu
authors.forename: Lina M
authors.initials: LM
authors.lastname: Felipez
authors.forename: Ranjana
authors.initials: R
authors.lastname: Gokhale
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Tierney
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Kirschner
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001799:Blood Sedimentation / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003251:Constriction, Pathologic; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005402:Fistula / Q000188:drug therapy* / Q000601:surgery; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000069285:Infliximab; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008297:Male; D017063:Outcome Assessment, Health Care; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D013792:Thalidomide; D000069285:Infliximab; D000068879:Adalimumab; D011241:Prednisone