Last Updated: June 8, 2007 (Reuters Health)

Natalizumab, a humanized immunoglobulin G4 monoclonal antibody targeting alpha-4 integrins, is more effective than placebo in treatment of certain patients with Crohn's disease and active inflammation.

"These studies confirm that natalizumab can treat active Crohn's disease patients," lead author Dr. Stephan R. Targan told Reuters Health. "If approved by the FDA, it will offer patients an alternative therapy with a different mechanism of action from therapies targeted to tumor necrosis factor."

In the May issue of Gastroenterology, Dr. Targan of Cedars Sinai Medical Center, Los Angeles and colleagues report the results of their study of 509 patients with moderately to severely active Crohn's disease and elevated C-reactive protein levels.

They were randomized to receive natalizumab 300 mg or placebo intravenously at the start of the study and 4 and 8 weeks later.

In all, 48% of natalizumab patients and 32% of placebo patients showed a decrease of 70 points or more in the Crohn's Disease Activity Index (CDAI) score at 8 through 12 weeks (p < 0.001). Active treatment patients also showed higher response rates at 4 and 8 weeks.

Sustained remission, defined as a CDAI score less than 150 points, was seen in 26% of natalizumab patients and 16% of placebo patients (p = 0.002), the investigators report.

Adverse event frequencies were similar in both groups, and in fact, "patients receiving placebo experienced more serious adverse events than those treated with natalizumab," the team found.

They note in their discussion of the results that elevated CRP identifies patients whose symptoms are likely driven by inflammation. Patients with other causes such as bile salt diarrhea or bacterial overgrowth are unlikely to benefit from agents targeting inflammatory pathways.

Nonetheless, the researchers advise that CRP "should not be the sole or the most important factor upon which treatment decisions are made." Factors such as endoscopic findings, the ESR, and response to prior treatments "should all be considered when attempting to determine appropriate patient treatment."

Summing up, Dr. Targan and colleagues conclude that taken together with data from previous induction trials, the findings "indicate that natalizumab is effective for induction of sustained response and remission in patients with Crohn's disease and active inflammation as evidenced by elevated CRP concentration and may represent an alternative treatment option ... in appropriately selected patients."

Date Posted: June 15, 2007