Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease.
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.
Selby
Warwick
W
Royal Prince Alfred Hospital, Sydney, Australia. warwicks@mail.med.usyd.edu.au
Pavli
Paul
P
Crotty
Brendan
B
Florin
Tim
T
Radford-Smith
Graham
G
Gibson
Peter
P
Mitchell
Brent
B
Connell
William
W
Read
Robert
R
Merrett
Michael
M
Ee
Hooi
H
Hetzel
David
D
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
D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; D017828:Rifabutin; D011239:Prednisolone; D002991:Clofazimine; D017291:Clarithromycin