Corticosteroids for induction of remission in Crohn's disease

Corticosteroids have been used for decades to treat active Crohn's disease. Controlled clinical studies that evaluated the effect of systemic corticosteroids to induce remission in Crohn's disease were reviewed. For inclusion in this analysis, studies could compare any form of corticosteroid that is systemically absorbed (e.g. prednisone, prednisolone, 6-methylprednisolone or hydrocortisone) to either placebo (fake medicine) or 5-aminosalicylates (e.g. mesalazine, mesalamine or sulfasalazine). Corticosteroids were found to be more effective than either placebo or 5-aminosalicylates at inducing remission in Crohn's disease. Although corticosteroids caused side effects more often in patients compared with placebo and 5-aminosalicylates, these side effects were not serious enough to cause withdrawal from the studies reviewed. In summary, corticosteroids are effective at inducing remission in patients with Crohn's disease. While they cause frequent side effects, these side effects were relatively minor in the reviewed studies, some of which followed patients for up to 24 weeks.

Authors' conclusions: 

Corticosteroids are effective for induction of remission in patients with CD, particularly when used for more than 15 weeks. Although corticosteroids cause more adverse events than either placebo or low-dose 5-ASA, these adverse events did not lead to increased study withdrawal in the included studies. Further information is required to determine the optimal duration of treatment and tapering protocol to maximize the efficacy of treatment with corticosteroids. Additionally, further study is required to determine whether corticosteroids are more effective in patients with certain phenotypes or when administered intravenously.

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Background: 

Historically, corticosteroids have been the most commonly used class of medication for induction of remission in Crohn's disease (CD). Corticosteroids down regulate production of inflammatory cytokines and interfere with NF-κB production, thereby blunting inflammatory response.

Objectives: 

The primary objective was to systematically review the efficacy and safety of traditional corticosteroids (given orally or intravenously) for induction of remission in CD.

Search strategy: 

The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group Specialized Trial Register, and ClinicalTrials.gov. No language restrictions were applied. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched.

Selection criteria: 

Randomized, controlled clinical trials of traditional, 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 (as defined by the study authors or validated clinical activity indices), receiving any formulation of systemically available corticosteroid by any oral or parenteral methods of delivery. The primary outcome was induction of remission of CD. Secondary outcomes included clinical response, change in mean CDAI, adverse events and the proportion of patients withdrawing due to adverse events.

Data collection and analysis: 

Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.

Main results: 

Two studies compared corticosteroids to placebo and six studies compared corticosteroids to 5-ASA. Corticosteroids were found to be significantly more effective than placebo at inducing remission in CD (RR 1.99; 95% CI 1.51 to 2.64; P < 0.00001). Corticosteroids were found to be more effective than 5-ASA at inducing remission in studies with long follow-up duration (i.e. > 15 weeks; RR 1.65; 95% CI 1.33 to 2.03; P < 0.00001). Corticosteroids induced adverse events in a higher proportion of patients than placebo (RR 4.89; 95% CI 1.98 to 12.07; P = 0.0006), or 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 adverse events when steroids were compared to high-dose 5-ASA. Steroids did not induce more study withdrawals due to adverse events than either placebo or 5-ASA.