Scolaris Content Display Scolaris Content Display

Aminosalicylates for induction of remission or response in Crohn's disease

This is not the most recent version

Abstract

available in

Background

Controlled clinical trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in patients with mildly to moderately active Crohn's disease.

Objectives

To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease.

Search methods

Separate MEDLINE (1966‐July 2010), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2010) and EMBASE database searches (1985‐July 2010) of all relevant English and non‐English language articles were performed, followed by manual searches of the reference list from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991‐2010) of the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG).

Selection criteria

Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included.

Data collection and analysis

Data extraction and assessment of methodological quality of each selected study was independently performed by the investigators and any disagreement was resolved by discussion and consensus. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Nineteen studies met the inclusion criteria and were analyzed. Pooled relative risks (RR) for inducing remission or clinical response and their 95% confidence intervals were calculated (random effects model) where appropriate.

Main results

Sulfasalazine was more likely to induce remission (RR 1.38; 95% CI 1.02 to 1.87; n = 263) compared to placebo with benefit confined mainly to patients with colitis. Sulfasalazine was less effective than corticosteroids (RR 0.66; 95% CI 0.53 to 0.81; n = 260). Olsalazine was less effective than placebo in a single trial. Low dose mesalamine (1 to 2 g/day) was not superior to placebo (RR = 1.46, 95% CI 0.89‐2.40; n = 302) and was less effective than corticosteroids. High dose mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02; 95% CI 0.75 to 5.45) or response (Weighted Mean Difference ‐19.8 points; 95% CI ‐46.2 to 6.7; n = 615). In a single randomized controlled trial, 5‐ASA was inferior to budesonide (RR 0.56; 95% CI 0.40 to 0.78). No statistically significant difference was found between high dose mesalamine and conventional corticosteroids (RR 1.04; 95% CI 0.79 to 1.36; n = 178). However, relatively few patients were available for analysis. There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations.

Authors' conclusions

Sulfasalazine has modest efficacy compared to placebo and is inferior to corticosteroids for the treatment of mild to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3 to 4.5 g/day) is not more effective than placebo for inducing response or remission. High dose mesalamine was inferior to budesonide for inducing remission in a single trial. In conclusion, sulfasalazine shows modest efficacy for the treatment of active Crohn's disease. However, the existing data show little benefit for 5‐aminosalicylates.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

available in

Aminosalicylates for treatment of active Crohn's disease

Crohn's disease is a chronic inflammatory disease of the intestines. Although Crohn's disease is often found in the ileum (the lower part of the small intestine), it can occur in any part of the digestive tract, from the mouth to the anus. The most common symptoms of Crohn's disease are diarrhea and abdominal pain which often occurs in the lower right region of the abdomen. Aminosalicylates are thought to treat Crohn's disease by reducing the inflammation of the intestines caused by the disease. Nineteen studies were reviewed. The studies compared aminosalicylates (sulfasalazine, mesalazine and mesalamine) with placebo (inactive pills or tablets) corticosteroids or budesonide (a steroid that is rapidly metabolized by the body and has less side‐effects than traditional corticosteroids) and found that sulfasalazine provides a modest benefit for the treatment of mild to moderately active Crohn's disease compared to placebo and is inferior to corticosteroids for treatment of active Crohn's disease. Sulphasalazine differs from other aminosalicylates in that it contains a sulpha portion that has been eliminated in the other preparations. Mesalazine and mesalamine formulations are not effective for inducing remission in active Crohn's disease. Budesonide was compared with high dose mesalamine (3 to 4.5 g/day) and was more effective for inducing remission. Aminosalicylates are safe for patients with Crohn's disease. Side effects are generally mild in nature and typically include nausea, vomiting, diarrhea, abdominal pain and dyspepsia (upset stomach or indigestion). In conclusion, sulfasalazine is modestly effective for the treatment of active Crohn's disease. However, the existing data show little benefit for mesalamine.