Findings published today in The New England Journal of Medicine from a first-of-its-kind comparator trial evaluating the anti-tumor necrosis factor (TNF)-alpha biologic treatment REMICADE (infliximab) in the treatment of moderately to severely active Crohn's disease in patients who were naive to immunomodulator and biologic therapy, showed that a significantly greater proportion of patients receiving REMICADE achieved steroid-free remission and mucosal healing compared with patients receiving azathioprine.
The results of the Phase 4 Study of Biologic and Immunomodulator Naive Patients in Crohn's (SONIC) clinical trial published in today's New England Journal of Medicine is the first of its kind to compare REMICADE, an anti-TNF-alpha therapy, with an immunomodulator (azathioprine) in patients with moderate to severe Crohn's disease. Azathioprine (AZA) is not approved by the United States Food and Drug Administration (FDA) for the treatment of Crohn's disease; however, it is widely used by gastroenterologists and other physicians in the U.S. to treat patients with Crohn's disease. Azathioprine is approved for the treatment of Crohn's disease in some countries outside the U.S.
Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that affects approximately 500,000 Americans. Symptoms of the disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss and fever. The cause of Crohn's disease is not known.
"As the first trial to compare an anti-TNF therapy with an immunomodulator in patients who have failed 5-ASA and/or steroids, the SONIC trial has the potential to change how we currently treat patients with moderate to severe Crohn's disease," said Dr. Jean-Frederic Colombel, Professor of Hepatogastroenterology, Centre Hospitalier Universitaire de Lille (France) and principal investigator. "The results provide new insights into the benefits of starting REMICADE alone or in combination with azathioprine -- earlier in the treatment of moderate to severe Crohn's disease."
Investigators reported that at the week 26 primary endpoint of the trial, 57 percent of patients receiving REMICADE combination therapy (REMICADE and azathioprine together) and 44 percent of patients receiving REMICADE monotherapy achieved steroid-free remission compared with 30 percent of patients receiving azathioprine alone (P<0.001 REMICADE with azathioprine vs. azathioprine monotherapy;>0.006 REMICADE monotherapy vs. azathioprine monotherapy;>0.02 REMICADE with azathioprine vs. REMICADE monotherapy).
In addition to improved rates of steroid-free remission in patients receiving REMICADE, the data showed that a greater proportion of patients receiving REMICADE achieved mucosal healing (i.e. complete absence of mucosal ulceration at week 26 in patients with mucosal ulcerations at baseline) a secondary endpoint of the study. Forty-four percent of patients receiving REMICADE combination therapy and 30 percent receiving REMICADE monotherapy achieved mucosal healing compared with 17 percent of patients receiving azathioprine alone (P<0.001 REMICADE with azathioprine vs. azathioprine monotherapy; >
Patients participating in the SONIC study through 30 weeks were given the option of continuing in a blinded study extension through 50 weeks. At week 50, REMICADE showed similar significant therapeutic benefit over azathioprine monotherapy.
The data also showed that the safety profile of REMICADE in combination or as monotherapy was similar to that of azathioprine monotherapy in the study. Through week 30, 24 percent of patients receiving azathioprine monotherapy experienced one or more serious adverse events compared with 16 and 14 percent of patients receiving REMICADE monotherapy and REMICADE with azathioprine, respectively. This includes two patients receiving azathioprine monotherapy who developed colon cancer, one patient receiving azathioprine monotherapy who died following a colectomy and one patient receiving REMICADE combination therapy who was diagnosed with tuberculosis. Serious infections were reported in 6 percent of patients in the azathioprine monotherapy group, 5 percent in the REMICADE monotherapy group and 4 percent in the REMICADE combination therapy group.
A final safety analysis for the entire study included data through week 54. The proportion of patients with one or more serious adverse events during the study was 27 percent>
In 1998, REMICADE became the first anti-TNF-alpha therapy approved by the FDA for the treatment of moderately to severely active Crohn's disease for the reduction of the signs and symptoms in patients who have an inadequate response to conventional therapy. During the past decade, REMICADE has also become the first and only anti-TNF-alpha therapy approved by the FDA for the treatment of moderately to severely active ulcerative colitis, in patients with an inadequate response to conventional therapy, a related inflammatory bowel disease. REMICADE is also approved for the treatment of pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapies.
SOURCE Centocor Ortho Biotech, Inc.