Two-year Combination Antibiotic Therapy With Clarithromycin, Rifabutin, and Clofazimine for Crohn's Disease

Gastroenterology. 2007 Jun;132(7):2313-9. doi: 10.1053/j.gastro.2007.03.031. Epub 2007 Mar 21.

Abstract

Background & aims: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Clarithromycin / administration & dosage*
  • Clarithromycin / adverse effects
  • Clarithromycin / therapeutic use
  • Clofazimine / administration & dosage*
  • Clofazimine / adverse effects
  • Clofazimine / therapeutic use
  • Crohn Disease / drug therapy*
  • Crohn Disease / microbiology*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium Infections / complications*
  • Mycobacterium avium / classification*
  • Patient Compliance
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use
  • Rifabutin / administration & dosage*
  • Rifabutin / adverse effects
  • Rifabutin / therapeutic use
  • Treatment Failure

Substances

  • Anti-Bacterial Agents
  • Glucocorticoids
  • Rifabutin
  • Prednisolone
  • Clofazimine
  • Clarithromycin