An open-label extension study of the CHARM and GAIN studies, performed in Abbott labs, demonstrate that patients with moderate-to-severe Crohn’s disease who are treated with HUMIRA® (adalimumab) actually achieved long-term clinical remission and a full clinical response respectively. This information was presented on May 21, 2008 at Digestive Disease Week® (DDW) in San Diego. DDW is the largest international gathering of physicians, researchers, and academics from the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Crohn’s Disease (CD) is a gastrointestinal disorder which is indicated by chronic inflammation of the wall of the digestive tract. The disease involves constant cycles of flare-ups and remission throughout the life of the patient. It is considered an inflammatory bowel disease (IBD), similar to ulcerative colitis, It can affect people of all ages, but is generally a disease of young adults, and most patients will experience onset before age 40. It affects more than 500,000 Americans, and over the course of the disease, up to 75% of all Crohn’s patients will undergo surgery for complications because the disease is resistant to treatment. Common symptoms include diarrhea, cramping, abdominal pain, weight loss, fever, and occasionally rectal bleeding.
HUMIRA, or Adalimumab, works by binding Tumor Necrosis Factor α (TNF-α), an important part of the immune response pathway — in this way it is related to infliximab and other TNF-α blockers.To date, it has been approved in 75 countries, and more than 250,000 patients are presently being administered HUMIRA. It is indicated for reducing signs and symptoms, as well as maintaining clinical remission in adult patients who haeve moderately to severely active CD, who have had inadequate response to conventional therapies, or if they have lost response or are intolerent to infliximab. HUMIRA has been approved for treatment of many autoimmune diseases such as CD, psoriasis, ankylosing spondylitis, and many types of arthritis including: rheumatoid, juvenile idiopathic, psoratic, and severe chronic plaque arthritis. Presently, clinical trials are in progress to evaluate the potential use of HUMIRA in other immune-mediated diseases.
The Crohn’s trial of the fully Human antibody Adalimumab for Remission Maintenance (CHARM) examined 854 patients with moderate to severe Crohn’s disease, in order to study HUMIRA’s efficacy in maintaining clinical remission. After four weeks of treatment, the 778 patients were blindly randomized to a placebo, HUMIRA dosed every week, or to the same dosage of HUMIRA administered half as often. At or after week 12, patients without remission were given the option of either of the non-placebo treatments for further therapy. The study evaluated clinical remission at weeks 26 and 56 for the HUMIRA groups compared to the placebo group. There was a significant improvement in clinical remission rates in HUMIRA treated patients in contrast to the placebo.
In the Gauging Adalimumab effectiveness in Infliximab Nonresponders (GAIN) study, 325 patients who had lost repsonse or were intolerent to infliximab were examined in a four week induction trial. In this study, three times as many HUMIRA patients reached clinical remission at week four in comparison to the placebo (21% versus 7%.)
The study reported at DDW was an open-label extension study (OLE) to focus on HUMIRA’s ability to maintain remission and achieve response in the long term follow up period. A diverse set of CD patients with moderate to severe Crohn’s disease were included, including those native to anti-TNF agents and those who had lost reponse or were intolerent to infliximab. Patients at the end of CHARM and the GAIN study were given HUMIRA every other week and the CHARM study received their previous regimens. Based on flare or non-response, patients were able to switch into the higher, every week, dosage. The results were pooled for analysis.
Response was measured by a change in the Crohn’s Disease Activity Index (CDAI), which is a weighted composite of eight clinical factors to evaluate patients wellness, including: daily number of liquid or very soft stools, severity of abdomincal pain, and levels of general well-being. Clinical remission was identified as a score of less than 150, and a clinical response was measured as a decline of 70 or more points.
The CHARM arm of the extension data showed that three quarters of patients (77%) taking HUMIRA, in remission at the end of the study, maintained clinical remission for an additional year. The gain GAIN extension data showed that, in the patients with a clinical response at four weeks, approximately 65% maintained clinical response at one year, while 40% remained in clinical remission.
“Crohn’s disease is a life-long condition with no known cure. One of the goals of treatment is to induce and maintain remission, which can help patients with their chronic symptoms,” said Remo Panaccione, M.D., Associate Professor, and Director of the Inflammatory Bowel Disease Clinic at the University of Calgary. “In this study, many patients taking HUMIRA during a lengthened treatment period showed clinical response and remission, which translates into improvement of disease symptoms. ”
Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott, concludes with additional support for the drug. “HUMIRA’s ability to effectively treat the chronic symptoms of Crohn’s disease makes it an important option for gastroenterologists and patients looking for improved disease management.”
More information about HUMIRA, including full prescribing information and Medication Guide, is available on the Web site www.humira.com or in the United States by calling Abbott Medical Information at 1-800-633-9110.
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, the American Gastroenterological Association (AGA) Institute, the American Society
for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 17-22, 2008, at the San Diego Convention Center, San Diego, CA. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.
Abbott is a global, broad-based health care company devoted to the discovery,development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries. Abbott’s news releases and other information are available on the company’s Web site at www.abbott.com.
Written by Anna Sophia McKenney