OP16. Adding ciprofloxacin to adalimumab results in a higher fistula closure rate in perianal fistulizing Crohn's disease [on behalf of ICC (Initative on Crohn's and Colitis)]
P. Dewint1, B. Hansen1, E. Verhey1, B. Oldenburg2, D.W. Hommes3, M. Pierik4, C. Ponsioen5, H. van Dullemen6, M.G. Russel7, A. van Bodegraven8, C.J. van der Woude1
1Erasmus Medical Center, Department of Gastroenterology & Hepatology, Rotterdam, Netherlands; 2University Medical Centre Utrecht, Department of Gastroenterology, Utrecht, Netherlands; 3UCLA, Division of Digestive Diseases, Los Angeles, United States; 4Maastricht University Medical Center, Dept of Gastroenterology, Maastricht, Netherlands; 5Academic Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands; 6UMC Groningen, Gastroenterology, Groningen, Netherlands; 7Medisch Spectrum Twente, Gastroenterology, Enschede, Netherlands; 8VU University Medical Center, Gastroenterology, Amsterdam, Netherlands
Background: Both anti‑TNF agents and antibiotics have shown their efficacy for the closure of perianal Crohn's fistulas. The existence of an additive effect of combination therapy for fistula closure remains to be demonstrated.
Methods: A multicenter, double-blind, placebo controlled trial, supported by Abbott Laboratories, was conducted, evaluating adalimumab in combination with ciprofloxacin or placebo in the treatment of active fistulizing, perianal disease (ADAFI).
Seventy-four patients with Crohn's disease related perianal fistulas were enrolled. After randomization, all patients received induction therapy with adalimumab subcutaneously (160 mg on week 0, 80 mg on week 2), followed by maintenance therapy (40 mg every other week) and were co-treated with placebo or ciprofloxacin 500 mg twice daily for 12 weeks, depending on the randomization arm. The primary endpoint was clinical response, defined as a reduction of at least 50% of the number of draining fistulas from baseline to week 12.
Results: 37 patients were allocated to the placebo-treatment, whereas 35 patients received ciprofloxacin. The primary endpoint was met in 50% of placebo treated patients and in 74% of ciprofloxacin treated patients (p = 0.048). However, this difference did not remain significant (p = 0.453) at week 24, with clinical response in 55% of placebo treated patients versus 64% in the ciprofloxacin co-treatment arm.
Conclusions: For the induction of perianal fistula closure in Crohn's disease, combination therapy of adalimumab and ciprofloxacine is highly effective and can be advocated over adalimumab alone. After discontinuation of antibiotic therapy, the initial beneficial effect of co-administration on fistula closure rate is not maintained.