Advances being made with monoclonal antibodies for the treatment of GI disorders

CHICAGO, IL (June 2, 2009) — Monoclonal antibodies can be safely and successfully used for the treatment of several gastroenterological disorders according to data being presented at Digestive Disease Week® (DDW®) 2009. DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

“The use of monoclonal antibodies is rising for a number of gastroenterological disorders, such as inflammatory bowel disease” according to Nicholas J. Shaheen, MD, MPH, AGAF, University of North Carolina School of Medicine. “New indications for these treatments are continuing to be developed and the safety profile is better understood, making them good treatment options for patients with recurrent or chronic gastrointestinal diseases.”

One-Year Data from the SONIC Study: A Randomized, Double-Blind Trial Comparing Infliximab and Infliximab plus Azathioprine to Azathioprine in Patients with Crohn’s Disease Naïve to Immunomodulators and Biologic Therapy (Abstract #751f)

The use of infliximab (IFX) plus azathioprine (AZA) and infliximab monotherapy increase the likelihood of patients achieving long-term steroid-free clinical remission in patients with moderate to severe Crohn’s disease, according to a new study. This study represents the first time longer term outcome data has been available to show the advantages of the combination therapy and IFX monotherapy.

Crohn’s disease causes inflammation of the lining and wall of the large and/or small intestine. When inflamed, the lining of the intestinal wall is red and swollen, becomes ulcerated, and bleeds.

“Results of this study will provide practitioners and their patients with more clinical data on how to use these drugs most appropriately to most effectively treat Crohn’s disease,” said William J. Sandborn, MD, AGAF, professor of medicine and vice chair of the division of gastroenterology and hepatology, Mayo Clinic, Rochester. “For the first time, we have longer term outcome data on the advantages of combination therapy that will help guide our treatment of patients with Crohn’s disease.”

While IFX plus AZA is used in clinical practice, gastroenterologists have not been sure how to best treat patients with the combination treatment. This study randomized 508 patients who were naïve to immunomodulators to receive either IFX plus AZA, IFX plus placebo or AZA plus placebo for 30 weeks, with the option to continue in a blinded study extension through week 50. The proportion of the patients enrolled in the study extension who were in steroid-free remission at week 50 was 72.2 percent with IFX plus AZA, 60.8 percent with IFX monotherapy and 54.7 percent with AZA monotherapy. If it was assumed that participants who did not enroll in the extension trial did not experience steroid-free remission at week 50, then the proportion of the patients who were in steroid-free remission at week 50 was 46.2 percent with IFX plus AZA, 34.9 percent with IFX monotherapy and 24.1 percent with AZA monotherapy. The proportion of patients in the overall trial with serious infections was similar in all treatment groups. No new opportunistic infections, malignancies or deaths occurred during this study extension.

Since this was a comparative effectiveness trial, patients were started on biologics earlier in the course of their Crohn’s disease than would occur in typical practice. The study used a CDAI score to measure clinical symptoms and for the first time in a Crohn’s disease clinical trial, investigators conducted several colonoscopies on all study participants to better identify the effectiveness of the treatment regimen, according to Dr. Sandborn.

Dr. Sandborn will present these data on Tuesday, June 2 at 3:30 p.m. CDT in Room E451B, McCormick Place.

Phase II Efficacy of Human Monoclonal Antibody Treatment to Prevent C. difficile Recurrence (Abstract 751b)

The use of two different monoclonal antibodies, CDA1 and CDB1, administered together along with standard of care antibiotics, reduces the risk of recurrence of C. difficile diarrhea, according to results of a study presented by researchers from MassBiologics of the University of Massachusetts Medical School, Boston, and Medarex, Inc., Princeton, NJ. Of note, the treatment showed efficacy for the BI/Nap1/027 epidemic strain as well as for those with multiple prior episodes of C. difficile diarrhea. Results also suggest an effect in reducing the severity of infection of the first episode of disease, and reduction of additional hospitalizations although further study will be needed to confirm these results. The combination was well tolerated with a good safety profile.

Recurrence of C. difficile is a major medical problem with the emergence of an epidemic hypervirulent strain and estimates of the disease occurrence keep climbing. Patients who experience one recurrence have a 25 percent chance of a second episode and patients having more than one episode of C. difficile diarrhea have up to a 60 percent chance of recurrence.

C. difficile diarrhea is a world-wide epidemic that is on the rise,” said Donna Ambrosino, MD, from MassBiologics and senior investigator of the study. “We need new approaches to prevent the recurrence of C. difficile to decrease morbidity, hospitalizations and health utilization costs.”

This randomized, double-blind, placebo-controlled phase II study examined attacking the problem of C. difficile differently, as an antibody approach that has never been previously examined. Earlier approaches have included the use of antibacterials/antibiotics or “tying up” the toxins upon exposure.

In this study, 200 patients from 30 clinical sites received either CDA1+CDB1 (101 patients) or placebo (99 patients) in addition to standard of care antibiotics. Treatment with CDA1+CDB1 resulted in a 70 percent reduction in recurrence rate in a complete intent to treat analysis. Of those who received CDA1+CDB1 treatment for the initial episode of C. difficile, 29.7 percent experienced severe diarrhea compared to 43.4 percent of those in the placebo group. Duration of initial hospitalization for patients was unaffected by CDA1+CDB1 (9.5 vs. 9.4 days), however exploratory analysis found that the affected proportion of patients who were subsequently hospitalized after infusion was significantly reduced (8.9 percent vs. 20 percent). All adverse events that reached significance were experienced by patients on the placebo arm, such as dehydration (0 percent vs. 5 percent) and low blood pressure (0 percent vs. 7 percent).

The study was funded by MassBiologics of the University of Massachusetts Medical School, and Medarex, Inc., who are equal partners in developing the product.

Dr. Israel Lowy, from Medarex, will present these data on Tuesday, June 2 at 2:15 p.m. CDT in Room E451B, McCormick Place.

Digestive Disease Week® 2009 (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 30 — June 4, 2009 in Chicago, IL. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

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