Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease

被引:259
作者
Selby, Warwick [1 ]
Pavli, Paul
Crotty, Brendan
Florin, Tim
Radford-Smith, Graham
Gibson, Peter
Mitchell, Brent
Connell, William
Read, Robert
Merrett, Michael
Ee, Hooi
Hetzel, David
机构
[1] Royal Prince Alfred Hosp, Sydney, NSW, Australia
[2] Canberra Hosp, Canberra, ACT, Australia
[3] Austin Hlth, Melbourne, Vic, Australia
[4] Mater Hlth Serv Adult Hosp, Brisbane, Qld, Australia
[5] Royal Brisbane Hosp, Brisbane, Qld 4029, Australia
[6] Royal Melbourne Hosp, Melbourne, Vic, Australia
[7] Launceston Gen Hosp, Launceston, Tas, Australia
[8] St Vincents Hosp, Melbourne, Vic, Australia
[9] Hornsby Ku Ring Gai Hosp, Sydney, NSW 2077, Australia
[10] Frankston Hosp, Melbourne, Vic, Australia
[11] Sir Charles Gairdner Hosp, Perth, WA, Australia
[12] Royal Adelaide Hosp, Adelaide, SA 5000, Australia
关键词
D O I
10.1053/j.gastro.2007.03.031
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 :5150) 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.
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收藏
页码:2313 / 2319
页数:7
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