Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn’s disease : a randomised controlled trial

Objective Crohn’s disease (CD) pathogenesis associated with dysbiosisand presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycinis active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazolealone in paediatric CD. Design This blinded randomised controlled trial allocated children 5–18 years with 10 12.5 or remission using intentionto treat analysis. Results 73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectindeclined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycinled to remission in 10/12 (83%). Conclusions The combination of azithromycinand metronidazolefailed to improve response but was superior for induction of remission and reduction in calprotectin. Trial registrationnumber NCT01596894.