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).
Author(s): Dewint P(1), Hansen BE, Verhey E, Oldenburg B, Hommes DW, Pierik M, Ponsioen CI,
van Dullemen HM, Russel M, van Bodegraven AA, van der Woude CJ.
Affiliation(s): Author information:
(1)Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, , Rotterdam,
The Netherlands.
Publication date & source: 2014, Gut. , 63(2):292-9
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.
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