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% takingantibiotics 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.
RCT Entities:
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.
Authors: Thaddeus S Stappenbeck; John D Rioux; Atsushi Mizoguchi; Tatsuya Saitoh; Alan Huett; Arlette Darfeuille-Michaud; Tom Wileman; Noboru Mizushima; Simon Carding; Shizuo Akira; Miles Parkes; Ramnik J Xavier Journal: Autophagy Date: 2011-04-01 Impact factor: 16.016
Authors: William Richard Berrington; Murdo Macdonald; Saraswoti Khadge; Bishwa Raj Sapkota; Marta Janer; Deanna Alisa Hagge; Gilla Kaplan; Thomas Richard Hawn Journal: J Infect Dis Date: 2010-05-01 Impact factor: 5.226