title: Effect of Thalidomide on Clinical Remission in Children and Adolescents with Ulcerative Colitis Refractory to Other Immunosuppressives: Pilot Randomized Clinical Trial.
abstract: BACKGROUND
  In a randomized controlled trial, thalidomide has shown to be effective in refractory Crohn's disease in children. This pilot study aimed at evaluating thalidomide in refractory pediatric ulcerative colitis (UC).
  
  
  METHODS
  Double-blind, placebo-controlled randomized clinical trial on thalidomide 1.5 to 2.5 mg/kg/day in children with active UC despite multiple immunosuppressive treatments. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks; all responders were followed up for a minimum of 52 weeks.
  
  
  RESULTS
  Twenty-six children with refractory UC were randomized to thalidomide or placebo. Clinical remission at week 8 was achieved by significantly more children treated with thalidomide {10/12 (83.3%) versus 2/11 (18.8%); risk ratio, 4.5 (95% confidence interval [CI], 1.2-16.4); P = 0.005; number needed to treat, 1.5}. Of the nonresponders to placebo who were switched to thalidomide, 8 of 11 (72.7%) subsequently reached remission at week 8 (risk ratio, 4.0 [95% CI, 1.1-14.7]; number needed to treat, 2.45; P = 0.01). Clinical remission in the thalidomide group was 135.0 weeks (95% CI, 32-238), compared with 8.0 weeks (95% CI, 2.4-13.6) in the placebo group (P < 0.0001). Cumulative incidence of severe adverse events was 3.1 per 1000 patient-weeks. Peripheral neuropathy and amenorrhea were the most frequent adverse events.
  
  
  CONCLUSIONS
  In this pilot randomized controlled trial on cases of UC refractory to immunosuppressive therapy, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and in longer term maintenance of remission. These findings require replication in larger clinical studies evaluating both thalidomide efficacy and safety.
authors.affiliation: *Institute for Maternal and Child Health IRCCS "Burlo Garofolo," Trieste, Italy; †Department of Paediatric Sciences, University of Messina, Messina, Italy; ‡Paediatric Gastroenterology Unit, Instituto Giannina Gaslini, Genoa, Italy; §Department of Sciences for Woman and Child Health, Meyer Children's Hospital, University of Florence, Florence, Italy; ‖Paediatric Department, Children's Hospital "V. Buzzi," Milan, Italy; ¶Department of Paediatric Gastroenterology, University of Pisa, Pisa, Italy; **University of Trieste, Trieste, Italy; and ††Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Lazzerini
authors.forename: Stefano
authors.initials: S
authors.lastname: Martelossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magazzù
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pellegrino
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Lucanto
authors.forename: Arrigo
authors.initials: A
authors.lastname: Barabino
authors.forename: Angela
authors.initials: A
authors.lastname: Calvi
authors.forename: Serena
authors.initials: S
authors.lastname: Arrigo
authors.forename: Paolo
authors.initials: P
authors.lastname: Lionetti
authors.forename: Monica
authors.initials: M
authors.lastname: Lorusso
authors.forename: Francesca
authors.initials: F
authors.lastname: Mangiantini
authors.forename: Massimo
authors.initials: M
authors.lastname: Fontana
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zuin
authors.forename: Gabriella
authors.initials: G
authors.lastname: Palla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.forename: Matteo
authors.initials: M
authors.lastname: Bramuzzo
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Pellegrin
authors.forename: Massimo
authors.initials: M
authors.lastname: Maschio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Stefania
authors.initials: S
authors.lastname: Manenti
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.forename: Sara
authors.initials: S
authors.lastname: De Iudicibus
authors.forename: Rossella
authors.initials: R
authors.lastname: Paparazzo
authors.forename: Marcella
authors.initials: M
authors.lastname: Montico
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D013792:Thalidomide / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide