title: Early change in faecal calprotectin predicts primary non-response to anti-TNFα therapy in Crohn's disease.
abstract: OBJECTIVE
  The early identification of primary non-response to anti-TNFα therapy facilitates the timely management of patients with Crohn's disease (CD). A recent, pilot study to detect prognostic markers of early response to anti-TNFα therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non-responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post-anti-TNFα induction can predict primary non-response.
  
  
  METHODS
  Retrospective study of 32 CD patients treated over a two-year period. Outcomes were assessed at 6 months based on clinical activity scores and the use of corticosteroids: (a) remission: Harvey-Bradshaw index (HBI) < 5, off corticosteroids >2 months; (b) response: drop in HBI >3, off corticosteroids; (c) non-response: ΔFCAL (and ΔCRP, respectively) was calculated as (FCAL post-induction - FCAL pre-induction) × 100/FCAL pre induction.
  
  
  RESULTS
  At 6 months, 23 (72%) patients had responded (median (interquartile range) HBI: 4 (3-5), FCAL: 55 (27-146)), 17 (73%) of whom were in remission [HBI: 3 (2.5-4) and FCAL: 42 (16-115)]. There was a significant difference in the ΔFCAL from baseline to post-induction in the three groups (p < 0.0001). Comparing non-responders to combined response and remission groups, the AUC of ΔFCAL to predict outcome at 6 months was 0.97. Using ROC analysis, a Δ70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR= 23). ΔCRP did not predict 6 months outcomes.
  
  
  CONCLUSIONS
  A drop in FCAL <70% after induction predicts primary non-response to anti-TNFα in CD.
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Polychronis
authors.initials: P
authors.lastname: Pavlidis
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Gulati
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dubois
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Chung-Faye
authors.affiliation: b Department of Biochemistry , Viapath Laboratory, King's College Hospital , Denmark Hill, London , UK.
authors.forename: Roy
authors.initials: R
authors.lastname: Sherwood
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bjarnason
authors.affiliation: a Department of Gastroenterology , King's College Hospital , Hill, London , Denmark, UK.
authors.forename: Bu'Hussain
authors.initials: B
authors.lastname: Hayee
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003424:Crohn Disease / Q000628:therapy*; D016208:Databases, Factual; D005243:Feces / Q000737:chemistry; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000069285:Infliximab / Q000008:administration & dosage*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: Anti-TNFα; Crohn’s; faecal calprotectin; primary non-response