Abstract
Background and Aims
The role of E.coli in Crohn[symbol]¯s disease pathogenesis is uncertain. This Phase 2a study aimed to assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E.coli inside macrophages.
Methods
Adults with active disease (CDAI>220 plus CRP¡Ý5mg/l and/or faecal calprotectin >250 ug/g) were randomised to receive (open label) oral budesonide (Entocort CR 9mg/day 8 weeks, 6mg/day 2 weeks, 3mg/day 2 weeks) or oral ciprofloxacin 500mg bd, doxycycline 100mg bd, hydroxychloroquine 200 mgs tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200mgs tds for 20 weeks. Use of anti-TNF in the previous 3 months was excluded. Primary endpoints were remission (CDAI =150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding by 10 weeks were invited to cross-over onto the alternative therapy.
Results
Fifty-nine patients were recruited across 8 sites. Including cross-over, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 6 months, 12 months, on intention to treat analysis including crossover 7/39, 6/39, 3/39 patients were in remission on antibiotics/hydroxychloroquine compared with 10/39, 1/39, 1/39 on budesonide (not significant). Withdrawals by 10 weeks due to adverse events were seen in 15 AB/HCQ and 6 budesonide. Nine of 24 patients receiving antibiotics/hydroxychloroquine per protocol were in remission at 24 weeks and 4/23 at 52 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location.
Conclusion
Long-term remissions with antibiotics/hydroxychloroquine are encouraging and justify a phase 3 study.
Registered at ClinicalTrials.gov NCT01783106
Year
2021
Category
Refereed journal