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

Arie Levine, Michal Kori, Jarek Kierkus, Rotem Sigall Boneh, Malgorzata Sladek, Johanna C. Escher, Eytan Wine, Baruch Yerushalmi, Jorge Amil Dias, Ron Shaoul, Gigi Veereman Wauters, Mona Boaz, Guila Abitbol, Athos Bousvaros, Dan Turner

Research output: Contribution to journalArticlepeer-review

Abstract

Objective Crohn's disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD. Design This blinded randomised controlled trial allocated children 5-18 years with 10<Pediatric Crohn's Disease Activity Index (PCDAI)≤40 to azithromycin 7.5 mg/kg, 5 days/week for 4 weeks and 3 days/week for another 4 weeks with metronidazole 20 mg/kg/day (group 1) or metronidazole alone (group 2), daily for 8 weeks. Failures from group 2 were offered azithromycin as open label. The primary end point was response defined by a decrease in PCDAI>12.5 or remission using intention to 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 calprotectin declined 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 azithromycin led to remission in 10/12 (83%). Conclusions The combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin. Trial registration number NCT01596894.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalGut
Volume68
Issue number2
DOIs
StatePublished - 1 Feb 2019

Keywords

  • Crohn's disease
  • antibiotics
  • azithromycin
  • inflammatory bowel disease
  • paediatric
  • therapy

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