Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI)
- Pieter Dewint1,
- Bettina E Hansen1,
- Elke Verhey1,
- Bas Oldenburg2,
- Daniel W Hommes3,
- Marieke Pierik4,
- Cyriel I J Ponsioen5,
- Hendrik M van Dullemen6,
- Maurice Russel7,
- Ad A van Bodegraven8,
- C Janneke van der Woude1
- 1Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, Rotterdam, The Netherlands
- 2Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
- 3Department of Gastroenterology and Hepatology, University Medical Center Leiden, Leiden, The Netherlands
- 4Department of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands
- 5Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
- 6Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, Groningen, The Netherlands
- 7Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands
- 8Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
- Correspondence to Dr C Janneke van der Woude, Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, ‘s Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands;
- Received 9 January 2013
- Revised 22 February 2013
- Accepted 22 February 2013
- Published Online First 23 March 2013
Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD).
Design Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80 mg week 0, 2), patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks. After 12 weeks, adalimumab was continued. Follow-up was 24 weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohn's Disease Activity Index, Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ).
Results Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed.
Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained.
Trial registration ClinicalTrials.gov Identifier: NCT00736983.