P579 Randomised open-label controlled trial of ciprofloxacin/doxycycline/hydroxychloroquine combination compared with standard budesonide in active Crohn’s disease (APRICOT)
J.M. Rhodes1, S. Subramanian2, P. Flanagan3, G. Horgan4, K. Martin2, J. Mansfield5, M. Parkes6, A. Hart7, H. Dallal8, T. Iqbal9, J. Butterworth10, K. Culshaw11, C. Probert1
1University of Liverpool, Institute of Translational Medicine, Liverpool- UK, UK, 2Royal Liverpool University Hospitals Trust, Gastroenterology, Liverpool, UK, 3Wirral University Teaching Hospital NHS Foundation Trust, Gastroenterology, Wirral, UK, 4Rowett Institute of Nutrition and Health, Biomathematics and Statistics Scotland, Aberdeen, UK, 5Newcastle upon Tyne Hospitals NHS Foundation Trust, Gastroenterology, Newcastle upon Tyne, UK, 6Cambridge University Hospitals NHS Foundation Trust, Gastroenterology, Cambridge, UK, 7St Mark’s Hospital- Harrow, Gastroenterology, London, UK, 8James Cook University Hospital, Gastroenterology, Middlesbrough, UK, 9Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Gastroenterology, Birmingham, UK, 10Shrewsbury and Telford Hospital NHS Trust, Gastroenterology, Shrewsbury, UK, 11University of Liverpool, Liverpool Cancer Trials Unit, Liverpool, UK
Background
Mucosal
Methods
Adult patients with active CD (CDAI>220 plus CRP≥5mg/l and/or faecal calprotectin >250 μg/g) were randomised to receive either standard oral budesonide (Entocort CR 9mg/day for 8 weeks, 6mg/day for 2 weeks, 3mg/day for 2 weeks) or antibiotics/hydroxychloroquine (AB/HCQ) - oral ciprofloxacin 500mg bd, doxycycline 100mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by continuation of doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for a further 20 weeks. The use of anti-TNF in the previous 3 months was an exclusion. Primary endpoint parameters were remission at 10 weeks, remission maintained through to 24 weeks, and remission maintained through to 52 weeks. Secondary endpoints included remission and/or response (fall in CDAI of >70) at 10 weeks and remission at 4 weeks. Patients who failed to respond by 10 weeks were invited to cross-over onto the alternative therapy.
Results
59 patients were recruited across 8 sites, lower than target (100) because 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). Withdrawals by 10 weeks due to adverse events were seen in 16 AB/HCQ, - including nausea (3), photosensitivity (2), Achilles pain (2) and activity of CD (4); and 7 budesonide. Although not significant when analysed per protocol, 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.
| Remission 10w | Remission maintained to 6m | Remission maintained to 12m | Rem. and/or response 10w | Remission 4week | |
| AB/HCQ | 7/27 | 6/24 (plus 3 10week responders in rem @ 6m) | 3/23 (plus 1 10week responder in rem @ 12m; plus 1 clin rem but WD UTI) | 15/27 | 8/30 |
| Budesonide | 10/34 | 1/32 | 1/31 | 13/34 | 9/38 |
Conclusion
The longer-term remissions seen in some patients receiving AB/HCQ are encouraging and a larger phase 3 study is justified.