Introduction Mucosal E. coli are increased in Crohn’s disease (CD). They replicate within macrophages and are then inaccessible to penicillins and gentamicin. Hydroxychloroquine is used with doxycycline to treat Whipple’s disease. It raises macrophage intra-vesicular pH and inhibits replication of bacteria that require acidic pH. Ciprofloxacin and doxycycline are also effective against E. coli within macrophages.
Methods Adult patients with active CD (CDAI>220 plus CRP≥5 mg/l and/or faecal calprotectin >250 ugram/g) were randomised to receive (open label) either oral budesonide (Entocort CR 9 mg/day 8 weeks, then 6 mg/day 2 weeks and 3 mg/day 2 weeks) or antibiotics/hydroxychloroquine (AB/HCQ) - oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mgs tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mgs tds for 20 weeks. Use of anti-TNF in the previous 3 months was an exclusion. 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 59 patients were recruited across 8 sites, lower than target (100) as recruitment slowed due to widening access to biologics. Including cross-over, 39 patients received AB/HCQ and 39 received budesonide. No significant differences were seen comparing AB/HCQ with budesonide at 10, 24 or 52 weeks on either intention-to-treat or per protocol analysis (see table 1). Withdrawals by 10 weeks due to adverse events were seen in 16 AB/HCQ and 7 budesonide. When patients on AB/HCQ who responded at 10 weeks and later remitted were included, 9/24 patients were in remission at 24 weeks and 4/23 at 52 weeks. No correlation was seen between response to AB/HCQ and ASCA/OmpC status.
Conclusions The long term remissions seen with AB/HCQ are encouraging and justify a phase 3 study.
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