Epidemiology

Azathioprine has changed the natural course of Crohn's disease

Last Updated: 2012-02-08 13:03:04 -0400 (Reuters Health)

By Will Boggs MD

NEW YORK (Reuters Health) - Early, aggressive use of azathioprine appears to have changed the typical course of Crohn's disease, Hungarian researchers say.

"This population-based study has demonstrated a significant change in the natural history of Crohn's disease over the last three decades," the researchers reported online January 10 in the American Journal of Gastroenterology.

Over that period they saw "reduced probability of disease behavior change, and reduced rates of surgery independently associated with increased and earlier azathioprine use."

This is the second of two papers "that confirm the long-term benefit of an early aggressive immunosuppressive therapy in Crohn's disease," said Dr. Peter Laszlo Lakatos from Semmelweis University in Budapest, in an email to Reuters Health.

"This is very reassuring since they are important proofs that the implementation of the new patient management is indeed altering the natural history," Dr. Lakatos said.

He added, "Most of us have already used this treatment strategy in the last five to 10 years."

Dr. Lakatos and colleagues used data on 506 Crohn's disease patients in the Veszprem province epidemiology database to analyze the evolution of surgical rates and medical therapy between 1977 and 2008.

They stratified patients according to year of diagnosis: 1977-1988 (74 patients), before azathioprine was widely used; 1989-1998 (199 patients), when azathioprine was generally started only after the first surgical resection; and 1999-2008 (233 patients) when azathioprine became more widely used earlier in the course of the disease.

The one- and five-year probability of azathioprine use increased with later years of diagnosis, from 3.2% and 6.2%, respectively, in the earliest group, to 11.4% and 29.9% in the middle group, and 34.8% and 46.2% in the most recent group.

Early azathioprine therapy (i.e., within three years of diagnosis) was significantly associated with an increased time to first resection, and the significant association between early and very early (within 1.5 years of diagnosis) azathioprine use and surgery requirements persisted after propensity score matching.

After excluding cases with resection within the first year of diagnosis, early (but not very early) azathioprine use was still significantly associated with an increased time to first resection in propensity score matched patients.

"Patients with a possible unfavorable phenotype (early disease, needing steroids early with severe flare, but hopefully without a complicated behavior) do require early aggressive therapy," Dr. Lakatos said. "Physicians should not wait until several clinical relapses or complicated disease behavior to upgrade therapy."

"The current therapeutic tools include the use of biologicals," Dr. Lakatos added. "Although clinical benefit is proven for the use of anti-TNFs, the benefit on long-term outcomes outside clinical studies is scant and outcomes from population based studies are awaited."

SOURCE: http://bit.ly/x2jEGc

Am J Gastroenterol 2012.