Budesonide for treatment of people with active Crohn's disease.

What is Crohn's disease?
Crohn's disease is a debilitating long-term (chronic) inflammatory bowel disease that can affect any part of the gastrointestinal tract from mouth to anus. Symptoms include abdominal pain, non-bloody diarrhea and weight loss. The most common initial treatment of the Crohn's disease is oral steroid therapy. Unfortunately, traditional steroids are usually absorbed into the body and cause significant unwanted side effects. These may include but are not limited to weight gain, diabetes, growth retardation, acne, mood instability, and high blood pressure. When people with Crohn's disease are experiencing symptoms of the disease it is said to be ‘active’; periods when the symptoms stop are called ‘remission’.

What is budesonide?
Budesonide is a steroid that is quickly metabolized by the liver thereby reducing corticosteroid-related side effects.

What did the researchers investigate?
The researchers investigated whether budesonide produces remission in people with active Crohn's disease; and whether these medications cause any harms (side effects). The researchers searched the medical literature up to June 12, 2014.

What did the researchers find?
The researchers identified 14 studies that included a total of 1805 participants. Nine studies (779 participants) compared budesonide to conventional corticosteroids, three studies (535 participants) compared budesonide to a placebo (e.g. a sugar pill), and two studies (491 participants) compared budesonide to mesalamine (an anti-inflammatory drug composed of 5-aminosalicylic acid). Ten studies were judged to be of high quality. Four studies were judged to be of low quality.

Budesonide was superior to placebo for induction of remission. An increase in side effects was not seen with budesonide compared to placebo. Withdrawals due to disease worsening were similar in budesonide and placebo groups. Budesonide patients were more likely than placebo patients to experience adrenal suppression a condition in which the adrenal glands do not produce adequate amounts of steroid hormones.

Budesonide was significantly less effective than conventional steroids for induction of remission in people with Crohn's disease. However, fewer side effects occurred in those treated with budesonide compared to conventional steroids and budesonide was better than conventional steroids in preserving adrenal function.

One study (n = 182) found budesonide to be superior to mesalamine for induction of remission in patients with Crohn's disease whereas another study found no difference in remission rates.

The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-aminosalicylic products. Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although budesonide is less effective than conventional steroids for induction of remission the likelihood of side effects and adrenal suppression is lower than with conventional steroids.

Authors' conclusions: 

Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression with budesonide is lower. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-ASA products.

Read the full abstract...
Background: 

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability.

Objectives: 

The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease.

Search strategy: 

The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, 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: 

Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion.

Data collection and analysis: 

Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria.

Main results: 

Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to conventional corticosteroids, three (535 patients) were placebo-controlled, and two (491 patients) compared budesonide to mesalamine. Ten studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to open label design. One study was judged to be at high risk of bias due to selective reporting. After eight weeks of treatment, 9 mg budesonide was significantly more effective than placebo for induction of clinical remission. Forty-seven per cent (115/246) of budesonide patients achieved remission at 8 weeks compared to 22% (29/133) of placebo patients (RR 1.93, 95% CI 1.37 to 2.73; 3 studies, 379 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (144 events). Budesonide was significantly less effective than conventional steroids for induction of remission at eight weeks. Fifty-two per cent of budesonide patients achieved remission at week 8 compared to 61% of patients who received conventional steroids (RR 0.85, 95% CI 0.75 to 0.97; 8 studies, 750 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to risk of bias. Budesonide was significantly less effective than conventional steroids among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Studies comparing budesonide to mesalamine were not pooled due to heterogeneity (I2 = 81%). One study (n = 182) found budesonide to be superior to mesalamine for induction of remission at 8 weeks. Sixty-eight per cent (63/93) of budesonide patients were in remission at 8 weeks compared to 42% (37/89) of mesalamine patients (RR 1.63, 95% CI 1.23 to 2.16). The other study found no statistically significant difference in remission rates at eight weeks. Sixty-nine per cent (107/154) of budesonide patients were in remission at 8 weeks compared to 62% (132/242) of mesalamine patients (RR 1.12, 95% CI 0.95 to 1.32). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better than conventional steroids in preserving adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78).

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