Ulcerative colitis: iv cyclosporine induced remission in steroid-resistant active disease.

Clinical bottom line (level 1b)

  1. Patients with severe ulcerative colitis resistant to steroid therapy who had intravenous cyclosporine were much more likely to go into remission (NNT = 1 at 7 days) .
  2. The effect on need for surgical intervention was unclear.
Lichtiger et al: New England Journal of Medicine 1994; 330: 1841-1845
Expires May 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: two university hospitals, USA

20 patients (aged range 18 to 65 years; mean 39, 55% female) admitted with severe ulcerative colitis with no response to intravenous steroids after more than seven days

Excluded if
  • bacterial or parasitic pathogens in stools, Clostridium difficile toxin, septicaemia
  • bowel perforation
  • active fungal or viral infection
  • uncontrolled hypertension
  • mercaptopurine or azathioprine therapy in previous two weeks
  • elevated serum hepatic enzymes, hyperbilirubinaemia, renal dysfunction, serum cholesterol < 3.1 mmol/l


    • Control Group: (n = 9, 9 analysed): placebo
    Experimental Group: (n = 11, 11 analysed): intravenous cyclosporine 4 mg/kg daily for up to 14 days. Dose was reduced if creatinine > 30% increase above baseline, serum liver enzymes > 50% increase above baseline, or diastolic blood pressure consistently > 90 mmHg despite antihypertensive medication
    All patients received hydrocortisone iv 100 mg every 8 hours and hydrocortisone enemas (100 mg in 60 ml) nightly. Patients continued mesalamine enemas, oral 5-ASA compounds and antibiotics if already on them.
    100% followed for 7 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no improvement in clinical activity score 7 days 9
    (100%)    		 2
    (18.2%)    		 82%
    (36% to 95%)    		 81.8%
    (59.0% to 105%)    		 1
    (1 to 2)
    surgery 7 days 4
    (44.4%)    		 2
    (18.2%)    		 59%
    (-75% to 90%)    		 26.3%
    (-13.4% to 65.9%)    		 4
    (NNT = 2 to infinity;
    NNH = 7 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    change in clinical activity score 1
    ()     		5
    ()     		p<0.001
    ( to )

  • The commonest side effects in patients on cyclosporine were paresthesias (36%) and hypertension (36%). One patient had a grand mal seizure.

    • Comments

    1. The study is too small to show any differences between the two groups in need for surgical intervention.

    Citation

    1. Lichtiger S, et al: cyclosporine in severe ulcerative colitis refractory to steroid therapy. New England Journal of Medicine 1994; 330: 1841-1845
    Search Terms: Crohn in Best Evidence
    Contributor: David Ford and Chris Ball, September 2000
    Reviewer:

    Clinical Question.
    Patient severe ulcerative colitis
    Intervention or Exposure cyclosporine
    Comparison placebo
    Outcome remission