title: Validation of endoscopic activity scores in patients with Crohn's disease based on a post hoc analysis of data from SONIC.
abstract: OBJECTIVE
  Mucosal healing might alter midterm and long-term outcomes of patients with Crohn's disease (CD) and has become an important end point in clinical trials. However, the minimal degree of mucosal improvement (endoscopic response) required to alter midterm outcomes is not known. We aimed to determine the best definition of endoscopic response by evaluating data on the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) from the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC trial).
  
  
  METHODS
  We analyzed data from 172 patients who participated in the SONIC trial, were found to have endoscopic lesions at baseline, and underwent a second endoscopic examination at week 26 of treatment with infliximab, azathioprine, or both. Mucosal healing was defined as absence of ulcers. A central reader calculated SES-CD and CDEIS results. Different cutoff values were set for endoscopic response based on the SES-CD or CDEIS. The diagnostic ability of these different cutoff values was evaluated using receiver operating characteristic (ROC) curves, positive likelihood ratios (PLR), and negative likelihood ratios (NLR). Corticosteroid-free clinical remission (CFREM) at week 50 was used as a binary classifier.
  
  
  RESULTS
  Based on analyses of ROC curves, PLR, and NLR, endoscopic response was defined as a decrease from baseline in SES-CD of at least 50%. At week 26, mucosal healing and endoscopic response were achieved in 48% and 65% of patients, respectively. Mucosal healing at week 26 was associated with CFREM at week 50, with 56% sensitivity, 65% specificity, a PLR of 1.60, and an NLR of 0.67. Endoscopic response at week 26 was associated with CFREM at week 50, with 74% sensitivity, 48% specificity, a PLR of 1.42, and an NLR of 0.54. Endoscopic response, defined as a decrease from baseline in CDEIS of at least 50%, yielded similar results.
  
  
  CONCLUSIONS
  In patients with CD, mucosal healing and endoscopic response (defined as a decrease from baseline in SES-CD or CDEIS of at least 50%) at week 26 of treatment identified those most likely to be in CFREM at week 50. The ability of the proposed endoscopic response cutoff value to predict midterm CFREM should be validated in an independent, prospective cohort. Its correlation with changes in long-term disease progression still needs to be demonstration. ClinicalTrials.gov, Number: NCT00094458.
authors: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. Electronic address: marc.ferrante@uzleuven.be.
authors: Marc
authors: M
authors: Ferrante
authors: Jean-Frederic
authors: JF
authors: Colombel
authors: William J
authors: WJ
authors: Sandborn
authors: Walter
authors: W
authors: Reinisch
authors: Gerassimos J
authors: GJ
authors: Mantzaris
authors: Asher
authors: A
authors: Kornbluth
authors: Daniel
authors: D
authors: Rachmilewitz
authors: Simon
authors: S
authors: Lichtiger
authors: Geert R
authors: GR
authors: D'Haens
authors: Christien J
authors: CJ
authors: van der Woude
authors: Silvio
authors: S
authors: Danese
authors: Robert H
authors: RH
authors: Diamond
authors: Alessandra Faria
authors: AF
authors: Oortwijn
authors: Kezhen L
authors: KL
authors: Tang
authors: Michael
authors: M
authors: Miller
authors: Freddy
authors: F
authors: Cornillie
authors: Paul J
authors: PJ
authors: Rutgeerts
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015599:Trauma Severity Indices; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab; D001379:Azathioprine
keywords: AUC; C-reactive protein; CD; CDAI; CDEIS; CFREM; CI; CRP; Crohn's Disease Activity Index; Crohn's Disease Endoscopy Index of Severity; Crohn's disease; IBD; MH; Mucosal Healing; NLR; PLR; Prognosis; REM; RESΔ100; RESΔ70; ROC; Response to Therapy; SES-CD; SMH; SONIC; Simple Endoscopic Score for Crohn's disease; Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease; area under the curve; clinical remission; clinical response with at least a 100-point reduction in Crohn's Disease Activity Index score; clinical response with at least a 70-point reduction in Crohn's Disease Activity Index score; confidence interval; corticosteroid-free clinical remission; mucosal healing; negative likelihood ratio; positive likelihood ratio; receiver operating characteristic; segmental mucosal healing