Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease.
Rhodes, Jonathan M Subramanian, Sreedhar Flanagan, Paul K Horgan, Graham W Martin, Kate Mansfield, John Parkes, Miles Hart, Ailsa Dallal, Helen Iqbal, Tariq
Rhodes, Jonathan M
Subramanian, Sreedhar
Flanagan, Paul K
Horgan, Graham W
Martin, Kate
Mansfield, John
Parkes, Miles
Hart, Ailsa
Dallal, Helen
Iqbal, Tariq
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2020-07-17
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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.
Trial registration: ClinicalTrials.gov NCT01783106.
Citation
Rhodes JM, Subramanian S, Flanagan PK, Horgan GW, Martin K, Mansfield J, Parkes M, Hart A, Dallal H, Iqbal T, Butterworth J, Culshaw K, Probert C. Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease. Dig Dis Sci. 2021 Aug;66(8):2700-2711. doi: 10.1007/s10620-020-06477-y. Epub 2020 Jul 17
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