*Note from CCFA's Patient Education Commitee: the role of 5-ASA for the active treatment and maintenance of ulcerative colitis is well established.*

Drug & Device Development

Uncertain role for 5-aminosalicylates in inflammatory bowel disease

Last Updated: 2011-04-05 17:23:05 -0400 (Reuters Health)

By Will Boggs MD

NEW YORK (Reuters Health) - 5-aminosalicylates (5-ASAs) don't prevent colorectal cancer in patients with inflammatory bowel disease (IBD) and may not induce remission or prevent relapse in patients with Crohn's disease, according to 2 reports in the March 15th online American Journal of Gastroenterology.
"Much of this promotion (that 5-ASA is chemoprophylactic) has been driven by industry rather than rigorous science," Dr. Charles N. Bernstein from University of Manitoba, Winnipeg, Manitoba, Canada told Reuters Health in an email. "I for one would like it to be true because these are easy drugs to take, but the balance of evidence does not support that it is true."

Dr. Bernstein and colleagues used date from their IBD database to investigate whether long-term use of 5-ASA was associated with a reduced risk of colorectal cancer. Their first study compared colorectal cancer incidence of patients that used 5-ASA with that of patients who didn't use 5-ASA, and their second study compared the use of 5-ASA in patients who developed colorectal cancer with that in matched controls.
In their first study, there was no difference in colorectal cancer incidence between patients who didn't use 5-ASA and patients who took 5-ASA for at least 1 year, for at least 5 years, or for at least 7.5 years. There was also no difference in colorectal cancer risk between ever-users and nonusers of 5-ASA.

In their second study, there was no significant difference in 5-ASA use among colorectal cancer cases versus controls.

"While biologically it may be appealing that 5-ASA may prevent carcinogenesis, and while it also may be appealing from the perspective of the agent being well tolerated and easy to take, the balance of data do not support that they actually work," Dr. Bernstein concluded.

"There is a substantive cost implication for asking patients who have been well for years and who do not want to take any drugs to simply stay on 5-ASA for cancer prevention when it is not substantiated. Even for those who advocate for its use there are little data to direct on dosing."

In a separate study, Dr. Alexander C. Ford from Leeds General Infirmary, Leeds, UK and colleagues in the US, Canada, and Australia conducted a systematic review of placebo-controlled trials of 5-ASAs examining their efficacy in inducing remission in active Crohn's disease as well as in preventing relapse in quiescent disease.

"The role of 5-ASAs in Crohn's disease is still uncertain, even though a previous Cochrane review said that they don't work and no future randomized controlled trials are required," Dr. Ford told Reuters Health by email. "In fact, more research is needed."

In this review of 22 randomized controlled trials, there was a trend towards a benefit of sulfasalazine over placebo in inducing remission, but no definite benefit of mesalamine over placebo.

Sulfasalazine and mesalamine were both ineffective in preventing relapse of quiescent Crohn's disease.
In remission studies and relapse trials, there was no statistically significant difference in the incidence of adverse events with 5-ASA compared with placebo.

"Ideally we need to know if 5-ASAs work in a particular group of Crohn's patients, e.g., those with isolated small bowel disease, those with only ileocecal disease, or those with only Crohn's colitis," Dr. Ford said. "Few of the previous randomized controlled trials have reported data according to these subgroups clearly, so it is impossible to answer this question at the present time. Future randomized controlled trials (if there are any!) should report efficacy data according to disease distribution."

"In the early course of the disease, before consideration of an immunosuppressant or biological is given, there may be a role for 5-ASAs," Dr. Ford explained. "Also, in patients with an acute flare in refusing or intolerant of glucocorticosteroids there is some evidence that 5-ASAs are better than placebo at inducing remission."

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Am J Gastroenterol 2011