Published in:
01-08-2021 | Doxycycline | Original Article
Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease
Authors:
Jonathan M. Rhodes, Sreedhar Subramanian, Paul K. Flanagan, Graham W. Horgan, Kate Martin, John Mansfield, Miles Parkes, Ailsa Hart, Helen Dallal, Tariq Iqbal, Jeffrey Butterworth, Kate Culshaw, Christopher Probert
Published in:
Digestive Diseases and Sciences
|
Issue 8/2021
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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.