JOURNAL ARTICLE
REVIEW

Budesonide for maintenance of remission in Crohn's disease

M Ellen Kuenzig, Ali Rezaie, Cynthia H Seow, Anthony R Otley, A Hillary Steinhart, Anne Marie Griffiths, Gilaad G Kaplan, Eric I Benchimol
Cochrane Database of Systematic Reviews 2014 August 21, (8): CD002913
25141071

BACKGROUND: Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events, particularly when corticosteroids are used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism and is effective for induction of remission in Crohn's disease.

OBJECTIVES: To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease.

SEARCH METHODS: The following databases were searched from inception to 12 June 2014: PubMed, MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched.

SELECTION CRITERIA: Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with quiescent Crohn's disease.

DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was maintenance of remission at various reported follow-up times during the study. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological, improvement in quality of life, adverse events and study withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference (MD) and 95% CI for continuous outcomes. Data were analysed on an intention-to-treat basis. The Chi(2) and I(2) statistics were used to assess heterogeneity. Random-effects models were used to allow for expected clinical and statistical heterogeneity. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria.

MAIN RESULTS: Twelve studies (n = 1273 patients) were included in the review: eight studies compared budesonide to placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, one compared budesonide to azathioprine, and one compared two doses of budesonide. Nine studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Nine studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to blinding and one of these studies also had inadequate allocation concealment. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months, 6 months or 12 months. At three months 64% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.25, 95% CI 1.00 to 1.58; 6 studies, 540 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to moderate heterogeneity (I(2) = 56%) and sparse data (315 events). At six months 61% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.15, 95% CI 0.95 to 1.39; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (238 events). At 12 months 55% of budesonide 6 mg patients remained in remission compared to 48% of placebo patients (RR 1.13; 95% CI 0.94 to 1.35; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (215 events). Similarly, there was no significant benefit for budesonide 3 mg compared to placebo at 6 and 12 months. There was no statistically significant difference in continued remission at 12 months between budesonide and weaning doses of prednisolone (RR 0.79; 95% CI 0.55 to 1.13; 1 study, 90 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (51 events) and high risk of bias (no blinding). Budesonide 6 mg was better than mesalamine 3 g/day at 12 months (RR 2.51, 95% CI 1.03 to 6.12; 1 study, 57 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (18 events) and high risk of bias (no blinding). There was no statistically significant difference in continued remission at 12 months between budesonide and azathioprine (RR 0.81; 95% CI 0.61 to 1.08; 1 study 77 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to sparse data (55 events) and high risk of bias (single-blind and no allocation concealment). The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (MD -24.30, 95% CI -46.31 to -2.29) and 12 months (MD -23.49, 95% CI -46.65 to -0.32) and mean time to relapse of disease (MD 59.93 days, 95% CI 19.02 to 100.84). Mean time to relapse was significantly shorter for patients receiving budesonide than for those receiving azathioprine (MD -58.00, 95% CI -96.68 to -19.32). Adverse events were not more common in patients treated with budesonide compared to placebo (6 mg: RR 1.51, 95% CI 0.90 to 2.52; 3 mg: RR 1.19, 95% CI 0.63 to 2.24). These events were relatively minor and did not result in increased rates of study withdrawal. Commonly reported treatment-related adverse effects included acne, moon facies, hirsutism, mood swings, insomnia, weight gain, striae, and hair loss. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg (RR 2.88, 95% CI 1.72 to 4.82) and 3 mg daily (RR 2.73, 95% CI 1.34 to 5.57) compared to placebo.

AUTHORS' CONCLUSIONS: These data suggest budesonide is not effective for maintenance of remission in CD, particularly when used beyond three months following induction of remission. Budesonide does have minor benefits in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
25141071
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"