title: Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI).
abstract: OBJECTIVE
  To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD).
  
  
  METHODS
  Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80 mg week 0, 2), patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks. After 12 weeks, adalimumab was continued. Follow-up was 24 weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohn's Disease Activity Index, Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ).
  
  
  RESULTS
  Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed.
  
  
  CONCLUSIONS
  Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00736983.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, , Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Dewint
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Elke
authors.initials: E
authors.lastname: Verhey
authors.forename: Bas
authors.initials: B
authors.lastname: Oldenburg
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.forename: Marieke
authors.initials: M
authors.lastname: Pierik
authors.forename: Cyriel I J
authors.initials: CI
authors.lastname: Ponsioen
authors.forename: Hendrik M
authors.initials: HM
authors.lastname: van Dullemen
authors.forename: Maurice
authors.initials: M
authors.lastname: Russel
authors.forename: Ad A
authors.initials: AA
authors.lastname: van Bodegraven
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012003:Rectal Fistula / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D002939:Ciprofloxacin; D000068879:Adalimumab
keywords: ANTIBIOTIC THERAPY; CROHN'S DISEASE; INFLAMMATORY BOWEL DISEASE