Crohn's disease: infliximab helped heal chronic abdominal or perianal fistulas.

Clinical bottom line (level 1b)

  1. Patients with chronic abdominal or perianal fistulas who received infliximab compared with placebo were more likely to have complete remission (NNT = 3 at 3 months) .
  2. Patients were more likely to have a 50% or more reduction in draining fistulas (NNT = 3 at 3 months) .
  3. There was no clear effect on the number of patients suffering adverse effects.
Present et al: New England Journal of Medicine 1999; 340 (18): 1398-1405
Expires May 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: twelve acute hospitals, USA and Europe

94 patients (aged mean 36 years, 53% female) with single or multiple draining abdominal or perianal fistulas for more than three months due to Crohn's disease (confirmed on radiography, endoscopy, or pathological examination)

Excluded if
  • <18 or >65 years old
  • on cyclosporine
  • treated with investigational agents or medication to reduce TNF-alpha within three months
  • other complications of Crohn's disease; current strictures or abscesses, presence of a stoma created within six months
  • history of allergy to murine proteins
  • previous treatment with infliximab


    • Note:
  • Patients were allowed to continue:
    • aminosalicylates (if stable for four weeks)
    • oral corticosteroids (at a dose 40 mg or less daily if stable for three weeks)
    • methotrexate (if given for three months at a dose stable for four weeks)
    • azathioprine or mercaptopurine (if given for six months at a dose stable for eight weeks)
    • antibiotics (if stable for four weeks)
  • Patients were stratified for the study centre and their number of fistulas.


    • Control Group: (n = 31, 31 analysed): placebo
    Experimental Group: (n = 63, 63 analysed): infliximab 5 mg/kg or 10 mg/kg intravenous at 0, 2 and 6 weeks

    100% followed for 34 weeks
    Outcome notes:
    • failure : success: 50% or more reduction from baseline in the number of draining fistulas on two or more consecutive visits (closure of fistula: no longer drained despite gentle finger compression)
    • adverse effects : headache, abscess, upper respiratory tract infection, fatigue

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    failure 34 weeks 23
    (74.2%)    		 24
    (38.1%)    		 49%
    (25% to 65%)    		 36.1%
    (16.6% to 55.6%)    		 3
    (2 to 6)
    incomplete response 34 weeks 27
    (87.1%)    		 34
    (54.0%)    		 38%
    (19% to 52%)    		 33.1%
    (16.1% to 50.2%)    		 3
    (2 to 6)
    adverse effects 34 weeks 20
    (64.5%)    		 47
    (74.6%)    		 -16%
    (-56% to 14%)    		 -10.1%
    (-30.1% to 9.89%)    		 -10
    (NNT = 10 to infinity;
    NNH = 3 to infinity)

  • There was no clear difference in effectiveness or side-effects in patients given 5 mg/kg or 10 mg/kg of infliximab.

    • Comments

    1. Infliximab is a genetically constructed IgG1 murine-human chimeric monoclonal antibody that binds both soluble subunit and the membrane-bound precursor of TNF-alpha.

    Citation

    1. Present DH, Rutgeerts P, Targan S, et al: Infliximab for the treatment of fistulas in patients with Crohn's disease. New England Journal of Medicine 1999; 340 (18): 1398-1405
    Search Terms: hand search
    Contributor: Chris Ball and Clare Wotton, September 2000
    Reviewer:

    Clinical Question.
    Patient chronic abdominal or perianal fistulas
    Intervention or Exposure infliximab
    Comparison placebo
    Outcome remission, side effects