title: Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide.
abstract: OBJECTIVE
  Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings.
  
  
  METHODS
  We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score.
  
  
  RESULTS
  Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006).
  
  
  CONCLUSIONS
  In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy. Electronic address: marzia.lazzerini@burlo.trieste.it.
authors.forename: Marzia
authors.initials: M
authors.lastname: Lazzerini
authors.affiliation: Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Pellegrin
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Martelossi
authors.affiliation: Paediatric Sciences, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magazzù
authors.affiliation: Paediatric Sciences, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pellegrino
authors.affiliation: Paediatric Sciences, University of Messina, Messina, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Lucanto
authors.affiliation: Paediatric Gastroenterology Unit, Institute Giannina Gaslini, Genoa, Italy.
authors.forename: Arrigo
authors.initials: A
authors.lastname: Barabino
authors.affiliation: Paediatric Gastroenterology Unit, Institute Giannina Gaslini, Genoa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Calvi
authors.affiliation: Paediatric Gastroenterology Unit, Institute Giannina Gaslini, Genoa, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Arrigo
authors.affiliation: Department of Sciences for Woman and Child Health, University of Florence, Meyer Children's Hospital, Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lionetti
authors.affiliation: Paediatric Department, Children's Hospital "V. Buzzi", Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fontana
authors.affiliation: Paediatric Department, Children's Hospital "V. Buzzi", Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zuin
authors.affiliation: Paediatric Gastroenterology, University of Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bramuzzo
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Maschio
authors.affiliation: Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Salemme
authors.affiliation: Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Manenti
authors.affiliation: Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lorenzi
authors.affiliation: University of Trieste, Trieste, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Montico
authors.affiliation: Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004724:Endoscopy; D005260:Female; D005500:Follow-Up Studies; D006651:Histocytochemistry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D015337:Multicenter Studies as Topic; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010919:Placebos; D013792:Thalidomide
keywords: Drug; Efficacy; IBD; Intestinal Mucosa