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TRADITIONAL CORTICOSTEROIDS FOR INDUCTION OF REMISSION IN CROHN DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
EI Benchimol1, C Seow2, AH Steinhart2, AM Griffiths1
1The Hospital for Sick Children, Toronto, Ontario; 2Mount Sinai Hospital, Toronto, Ontario
BACKGROUND: Historically, despite common adverse effects, corticosteroids have been the most commonly used class of medication to induce clinical remission in Crohn’s disease (CD). This review and meta-analysis examined the efficacy and toxicity of corticosteroids in induction of remission in CD.
METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Central Register, ClinicalTrials.gov), review articles, and conference proceedings were searched. Controlled clinical trials of systemic corticosteroids for the induction of remission of active CD were included in this review. Control groups included patients receiving either placebo or 5-aminosalicylates (5-ASA). The study population included patients of any age with active CD, receiving any formulation of traditional corticosteroid orally or parenterally. Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using Jadad’s criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity. Studies were then weighted using the DerSimonian & Laird or Mantel-Haenszel method.
RESULTS: Two studies compared corticosteroids to placebo and six studies compared corticosteroids to 5-ASA. When induction of clinical remission was assessed >15 weeks from start of treatment, corticosteroids proved more effective than placebo (RR 1.99, 95% CI 1.51 to 2.64, p < 0.00001) and than 5-ASA (RR 1.65, 95% CI 1.33 to 2.03, p < 0.00001) When likelihood of clinical remission was assessed earlier (at 4-6 weeks and at 10-12 weeks) corticosteroids were not found to be more effective than 5-ASA. Corticosteroids induced side effects in a higher proportion of patients compared to both placebo (RR 4.89, 95% CI 1.98 to 12.07, p = 0.0006), and to low-dose 5-ASA (RR 2.38, 95% CI 1.34 to 4.25, p = 0.003). No difference existed in the proportion of patients experiencing side effects comparing steroids to high-dose 5-ASA, nor did steroids induce more study withdrawals due to drug intolerance or adverse effects than either placebo or 5-ASA.
CONCLUSIONS: Corticosteroids are effective at inducing remission in patients with CD, when used for more than 15 weeks with dosage taper. Although corticosteroids cause more side effects than either placebo or low-dose 5-ASA, these adverse effects did not lead to increased study withdrawals.