Crohn's disease: an infusion TNF-alpha antibodies improves symptoms and chance of remission in active disease

Clinical bottom line (level 1b)

  1. Patients with moderately active Crohn's disease who receive a single infusion of anti-TNF-alpha antibodies are more likely to improve symptomatically (NNT = 4 at 12 weeks) and go into remission (NNT = 6 at 12 weeks) .
Targan et al: New England Journal of Medicine 1997; 337: 1029-1035
Expires May 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 18 acute hospitals, North America and Europe

108 patients (aged mean 37, 51% male) with moderately active Crohn's disease for at least six months (Crohn's disease activity index 220 to 400)

Excluded if
  • on mesalamine for less than 8 weeks or dose varied within previous 4 days
  • on > 40 mg corticosteroids per day, or on steroids for less than 8 weeks, or dose varied in last 2 weeks
  • on mercaptopurine or azathioprine for less than 6 months, or dose varied in last 8 weeks
  • history of allergy to murine proteins
  • prior treatment with murine, chimeric or humanized monoclonal antibodies
  • treatment with parenteral corticosteroids or corticotropin within 4 weeks)
  • received treatment with cyclosporine, methotrexate, or experimental agents in previous 3 months
  • symptomatic stenosis or ileal strictures
  • proctocolectomy or total colectomy
  • stoma


    • Note:
  • Patients were stratified for study centre and corticosteroid use before randomisation.


    • Control Group: (n = 25, 25 analysed): placebo
    Experimental Group: (n = 83, 83 analysed): cA2 5 mg/kg or 10 mg/kg or 20 mg/kg intravenously over 2 hours
    Patients continued on steroids, mesalamine and azathioprine or mercaptopurine during the study. Patients were not allowed to start any of these medications or cyclosporine or methotrexate during the study.
    100% followed for 12 weeks
    Outcome notes:
    • reduction in CDAI index > 70 points : at 4 weeks
    • remission : CDAI < 150 at 4 weeks
    • reduction in CDAI index > 70 points : at 12 weeks
    • remission : CDAI < 150 at 12 weeks

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    reduction in CDAI index > 70 points 4 weeks 4
    (16.0%)    		 54
    (65.1%)    		 310%
    (63% to 910%)    		 49.1%
    (31.4% to 66.7%)    		 2
    (1 to 3)
    remission 4 weeks 1
    (4.0%)    		 27
    (32.5%)    		 710%
    (16% to 5600%)    		 28.5%
    (15.9% to 41.2%)    		 4
    (2 to 6)
    reduction in CDAI index > 70 points 12 weeks 3
    (12.0%)    		 34
    (41.0%)    		 240%
    (14% to 920%)    		 29.0%
    (12.4% to 45.5%)    		 3
    (2 to 8)
    remission 12 weeks 2
    (8.00%)    		 20
    (24.1%)    		 200%
    (-24% to 1100%)    		 16.1%
    (2.03% to 30.2%)    		 6
    (3 to 49)

    Comments

    1. cA2 antibody binds to TNF-alpha
    2. No dose response was noted - however the study was too small to show any differences between the different doses.

    Citation

    1. Targan SR, Hanauer SB, van Deventer SJ, et al: a short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. New England Journal of Medicine 1997; 337: 1029-1035
    Search Terms: Crohn* in Cochrane
    Contributor: Chris Ball and Clare Wotton, October 1999
    Reviewer:

    Clinical Question.
    Patient active Crohn's disease
    Intervention or Exposure cA2 antibody to TNF-alpha
    Outcome remission