Clinical trial: randomized study of clarithromycin versus placebo in active Crohn's disease

Background Crohn's disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad-spectrum antibiotic that has good penetration into macrophages. Aim To assess the efficacy of clarithromycin in active Crohn's disease. Methods Patients with Crohn's disease activity index > 200 and serum C-reactive protein >= 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI <= 150) or response (fall in CDAI >= 70 from pre-treatment level) at 3 months. Results The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn's disease activity index was 35 (80) clarithromycin and -2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn's disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01). Conclusion Clarithromycin 1 g for 3 months is ineffective in active Crohn's disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance.