Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease



Rhodes, Jonathan M ORCID: 0000-0002-1302-260X, Subramanian, Sreedhar ORCID: 0000-0002-6483-1730, Flanagan, Paul K, Horgan, Graham W, Martin, Kate, Mansfield, John, Parkes, Miles, Hart, Ailsa, Dallal, Helen, Iqbal, Tariq
et al (show 3 more authors) (2020) Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease. Digestive Diseases and Sciences.

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Abstract

Background Increased mucosa-associated E. coli are present in Crohn’s disease, but their role in pathogenesis is uncertain. Aims To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. Methods Adults with moderately active disease (CDAI > 220–450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 μg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. Results Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. Conclusion Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

Item Type: Article
Uncontrolled Keywords: Crohn's disease, Antibiotics, Ciprofloxacin, Doxycycline, Hydroxychloroquine, E, coli
Depositing User: Symplectic Admin
Date Deposited: 18 Aug 2020 13:44
Last Modified: 09 Jan 2021 01:38
DOI: 10.1007/s10620-020-06477-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3098014