DDW 2009: Treatment-Refractory Crohn's Patients Respond to Combination Therapy in the SONIC Trial

Martha Kerr

June 04, 2009

June 4, 2009 (Chicago, Illinois) — One-year data from the Study of Immunomodulator Naive Patients in Crohn's Disease (SONIC) show that nearly three quarters of patients with Crohn's disease who failed to respond to initial treatment with conventional therapies respond to combination therapy with infliximab (Remicade, Centocor Ortho Biotech Inc) and azathioprine.

Response rates were significantly lower with monotherapy.

Results of SONIC were presented during a late-breaking clinical-trials session here at Digestive Disease Week 2009 by William J. Sandborn, MD, professor of medicine and vice-chair of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota.

In SONIC, 508 patients with refractory Crohn's disease were randomized to infliximab monotherapy, azathioprine monotherapy, or infliximab plus azathioprine combination therapy. Patients underwent colonoscopies at baseline and again at week 26. Patients were given the option of continuing in the open-label phase of the trial for another 30 weeks, which 280 patients did.

Patients who did not enter the study extension were assumed to be nonresponders or not in steroid-free remission at week 50.

For the entire 508-patient study group, steroid-free remission rates at 50 weeks were 46% in the combination group, 35% in the infliximab group, and 24% in the azathioprine group (combination vs azathioprine therapy, P < .001; infliximab vs azathioprine therapy, P = .028; combination vs infliximab therapy, P = .035).

For the subgroup of 280 patients in the extension phase, 72% of those in the combination group, 61% of those in the infliximab group, and 55% of those in the azathioprine group achieved steroid-free remission at week 50 (combination vs azathioprine therapy, P = .010; infliximab vs azathioprine therapy, P = .324; combination vs infliximab therapy, P = .065).

The serious adverse-event rate with 1 or more serious events at week 54 was 27% with azathioprine, 24% with infliximab, and 15% with combination therapy; all events occurred within the first 26 weeks of the study.

"These results are strong enough to change clinical practice," Dr. Sandborn said. "They certainly changed mine."

"Results of the colonoscopies were interesting," Dr. Sandborn told Medscape Gastroenterology after his presentation. "They showed that 20% to 25% of patients with symptoms of Crohn's disease have no signs of inflammation on the intestinal mucosa. These patients may not need anti-inflammatories. . . . The symptoms appear to be caused by something else."

He noted that the anti-inflammatory component of therapy carries the highest risk for adverse effects.

"The importance of these findings is that these drugs are frequently used in combination [off label]. It's extremely important to know what happens when you throw these things together," moderator Nicholas J. Shaheen, MD, MPH, associate professor of medicine and epidemiology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill, told Medscape Gastroenterology. "It appears that they are safer together than as monotherapy."

SONIC is supported by funding from Centocor Ortho Biotech, Inc., of Philadelphia, Pennsylvania. Dr. Shaheen has disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2009: Abstract 751f. Presented June 2, 2009.

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