title: A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).
abstract: BACKGROUND
  Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms.
  
  
  METHODS
  Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'.
  
  
  RESULTS
  136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up.
  
  
  CONCLUSIONS
  This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS.
  
  
  BACKGROUND
  NCT01316718.
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
authors.forename: Ching
authors.initials: C
authors.lastname: Lam
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Leighton
authors.affiliation: Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hastings
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lingaya
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
authors.forename: Yirga
authors.initials: Y
authors.lastname: Falcone
authors.affiliation: Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhou
authors.affiliation: FRAME laboratory, University of Nottingham, Nottingham, UK.
authors.forename: Luting
authors.initials: L
authors.lastname: Xu
authors.affiliation: Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Whorwell
authors.affiliation: Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Walls
authors.affiliation: Department of Histopathology, Nottingham University Hospital Trusts, Nottingham, UK.
authors.forename: Abed
authors.initials: A
authors.lastname: Zaitoun
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Montgomery
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Spiller
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine
keywords: 5-AMINOSALICYLIC ACID (5-ASA); DIARRHOEA; IRRITABLE BOWEL SYNDROME