title: Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease.
abstract: OBJECTIVE
  Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn's disease. We report a prospective, parallel, placebo-controlled, double-blind, randomized trial of 2 years of clarithromycin, rifabutin, and clofazimine in active Crohn's disease, with a further year of follow-up.
  
  
  METHODS
  Two hundred thirteen patients were randomized to clarithromycin 750 mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in addition to a 16-week tapering course of prednisolone. Those in remission (Crohn's Disease Activity Index <or=150) at week 16 continued their study medications in the maintenance phase of the trial. Primary end points were the proportion of patients experiencing at least 1 relapse at 12, 24, and 36 months.
  
  
  RESULTS
  At week 16, there were significantly more subjects in remission in the antibiotic arm (66%) than the placebo arm (50%; P=.02). Of 122 subjects entering the maintenance phase, 39% taking antibiotics experienced at least 1 relapse between weeks 16 and 52, compared with 56% taking placebo (P=.054). At week 104, the figures were 26% and 43%, respectively (P=.14). During the following year, 59% of the antibiotic group and 50% of the placebo group relapsed (P=.54).
  
  
  CONCLUSIONS
  Using combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for up to 2 years, we did not find evidence of a sustained benefit. This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn's disease in the majority of patients. Short-term improvement was seen when this combination was added to corticosteroids, most likely because of nonspecific antibacterial effects.
authors.affiliation: Royal Prince Alfred Hospital, Sydney, Australia. warwicks@mail.med.usyd.edu.au
authors.forename: Warwick
authors.initials: W
authors.lastname: Selby
authors.forename: Paul
authors.initials: P
authors.lastname: Pavli
authors.forename: Brendan
authors.initials: B
authors.lastname: Crotty
authors.forename: Tim
authors.initials: T
authors.lastname: Florin
authors.forename: Graham
authors.initials: G
authors.lastname: Radford-Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Gibson
authors.forename: Brent
authors.initials: B
authors.lastname: Mitchell
authors.forename: William
authors.initials: W
authors.lastname: Connell
authors.forename: Robert
authors.initials: R
authors.lastname: Read
authors.forename: Michael
authors.initials: M
authors.lastname: Merrett
authors.forename: Hooi
authors.initials: H
authors.lastname: Ee
authors.forename: David
authors.initials: D
authors.lastname: Hetzel
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002991:Clofazimine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy* / Q000382:microbiology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000150:complications*; D009162:Mycobacterium avium / Q000145:classification*; D010349:Patient Compliance; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D017828:Rifabutin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; D017828:Rifabutin; D011239:Prednisolone; D002991:Clofazimine; D017291:Clarithromycin