Newly Published Study Evaluates Abbott's HUMIRA(R) in Crohn's Disease

ABBOTT PARK, Ill., Jan. 31 /PRNewswire-FirstCall/ -- Patients with active Crohn's disease who have ceased responding to Remicade (infliximab) may respond to HUMIRA(R) (adalimumab), according to a new study in the January 2005 issue of the American Journal of Gastroenterology. The study found that 11 of 13 (85 percent) of Crohn's patients who had experienced a reduced or loss of response to infliximab -- currently the only FDA-approved biologic treatment for Crohn's disease -- experienced a reduction in disease activity with HUMIRA.

Crohn's disease is a serious chronic and inflammatory disease of the gastrointestinal tract that affects approximately 500,000 Americans and is typically diagnosed before age 30. Common symptoms of the disease include diarrhea, cramping, abdominal pain, weight loss, fever and in some cases rectal bleeding. There is no cure for Crohn's disease.

"Crohn's is a serious and complex disease with limited treatment options," said Konstantinos A. Papadakis, M.D., the lead study investigator from Cedars- Sinai Medical Center, Los Angeles. "We are very encouraged by the findings of this study and look forward to larger prospective studies to further assess HUMIRA in patients where infliximab is no longer an option."

About the Study

Papadakis and colleagues retrospectively evaluated the safety and efficacy of six months of therapy with HUMIRA in 15 patients with active Crohn's disease (CD) who experienced a reduced or loss of response to infliximab. All patients who received treatment had a diagnosis of moderate to severe active CD, were steroid-dependent and had failed standard immunomodulators and/or had experienced draining fistula despite concomitant medical therapy. Patients selected for the study had received a median of five infliximab infusions prior to treatment with HUMIRA and experienced a reduced or loss of response to infliximab as determined by their physicians.

Disease activity was scored according to the Harvey-Bradshaw clinical activity index (HBI), a clinical assessment of disease activity, which scores level of general well-being, severity of abdominal pain, number of liquid stools per day, and presence of abdominal mass and disease complications. Complete response was defined as an HBI of less than or equal to 4 and withdrawal of corticosteroid treatment; partial response was defined as a decrease of at least 50 percent in HBI and reduction in corticosteroid dose. All other patients were considered non-responders.

Trial participants initiated treatment with an 80 mg subcutaneous (under the skin) injection of HUMIRA followed by a 40 mg dose every two weeks. To maintain clinical response, the dose and/or dosing frequency was increased during the study; three patients received an increased dose of 80 mg every two weeks, two patients were given 80 mg weekly and one patient was given 120 mg every two weeks. Concomitant treatment with immunomodulators was continued.

Of the 13 patients who completed the study, seven (54 percent) had a complete response to treatment with HUMIRA, four (31 percent) had a partial response, and two (15 percent) were non-responders. Patients with extra- intestinal manifestations of CD (joint pain) (n=7) improved or resolved their symptoms with HUMIRA treatment, as did one patient who suffered from oral ulcers. Five of the 11 patients taking concomitant corticosteroid therapy were able to discontinue their use (by week 14 of treatment with HUMIRA) and three were able to decrease the dose (at last follow-up).

No severe adverse events were observed in this study. There was no evidence of immediate or delayed-type hypersensitivity reactions. The most frequent adverse event was injection site reaction characterized by erythema and discomfort lasting less than 24 hours.

Additional Data on HUMIRA in Infliximab-Intolerant Patients Recently Published

The Papadakis study follows research published recently in the Journal of American Gastroenterology on HUMIRA in Crohn's patients with loss of response or intolerance to infliximab. In that 12-week, open-label study led by William J. Sandborn, M.D., Mayo Clinic, and Stephen Hanauer, M.D., University of Chicago, 24 patients received 40 mg of HUMIRA every other week following an initial 80 mg dose, all given via subcutaneous injection.

The study assessed the safety of HUMIRA as well as the Crohn's Disease Activity Index (CDAI) score. CDAI is a weighted composite score of eight clinical factors, including a daily number of liquid or very soft stools, severity of abdominal pain, level of general well-being, presence of extra- intestinal manifestations or abdominal mass, use of anti-diarrheal agents, hematocrit and decrease in standard body weight. Clinical response was defined as a decrease in the CDAI by at least 100 points, in patients whose baseline CDAI score was at least 220. The primary efficacy variable was the induction of clinical remission, defined as a CDAI score of less than 150 at week four in the subset of patients who had a baseline CDAI score of at least 220 points.

Seventeen of the 24 patients (71 percent) had baseline CDAI scores of at least 220. At four- and 12-week follow up, clinical remission occurred in two (12 percent) and five (29 percent) patients, respectively, while clinical response occurred in seven (41 percent) and 10 (59 percent) patients, respectively. Of the nine patients who had draining fistulas, five (56 percent) experienced a decrease in the number of draining fistulas and three (33 percent) had complete fistula closure at week 12.

Study participants who did not achieve clinical remission and complete fistula closure or complete steroid withdrawal could escalate the dosing schedule to 40 mg weekly after the fourth week of therapy. Nineteen patients (79 percent) escalated their dose between weeks four and six.

All 24 patients were able to tolerate HUMIRA. The most common adverse events included upper respiratory tract infection and headache.

"Given the outcome of both studies, we are excited to continue evaluating the potential of HUMIRA in Crohn's," said Becky Hoffman, M.D., global project head, immunology, Abbott.

Important Safety Information

Cases of tuberculosis (TB) have been observed in patients receiving HUMIRA. Serious infections and sepsis, including fatalities, have been reported with the use of TNF-blocking agents, including HUMIRA. Many of these infections occurred in patients also taking other immunosuppressive agents that in addition to their underlying disease could predispose them to infections. The combination of HUMIRA and anakinra is not recommended.

TNF-blocking agents, including HUMIRA, have been associated in rare cases with demyelinating disease and severe allergic reactions. Infrequent reports of serious blood disorders and rare reports of lymphoma have been reported with TNF-blocking agents. Patients with rheumatoid arthritis, particularly those with highly active disease are at a higher risk for the development of lymphoma. The potential role of TNF-blocking therapy in the development of malignancies is not known.

The most frequent adverse events seen in the placebo-controlled clinical trials in rheumatoid arthritis (HUMIRA vs. placebo) were injection site reactions (20 percent vs. 14 percent), upper respiratory infection (17 percent vs. 13 percent), injection site pain (12 percent vs. 12 percent), headache (12 percent vs. 8 percent), rash (12 percent vs. 6 percent) and sinusitis (11 percent vs. 9 percent). Discontinuations due to adverse events were 7 percent for HUMIRA and 4 percent for placebo. As with any treatment program, the benefits and risks of HUMIRA should be carefully considered before initiating therapy.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved by the FDA for reducing the signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). HUMIRA can be used alone or in combination with methotrexate or other DMARDs. HUMIRA offers convenient every-other-week dosing by subcutaneous injection (shot beneath the skin) via a specially designed pre-filled syringe. The recommended dose of HUMIRA for adult patients with RA is 40 mg every other week.

HUMIRA is the first fully human monoclonal antibody approved in Europe for RA, and the first tumor necrosis factor alpha (TNF-a) antagonist approved with an indication for use with methotrexate or as monotherapy. To date, HUMIRA has been approved in 54 countries and prescribed to more than 83,000 patients suffering from rheumatoid arthritis worldwide.

Clinical trials are currently underway evaluating the potential of HUMIRA in other autoimmune diseases.

HUMIRA was discovered through a broad scientific collaboration between Abbott and Cambridge Antibody Technology (CAT). As part of the collaboration, Abbott had the right to select several target antigens for which a joint Abbott/CAT research team would discover human antibody therapeutics. HUMIRA was isolated and optimized by Abbott and CAT as part of this collaboration. Abbott owns exclusive worldwide rights to HUMIRA, including responsibility for clinical development, manufacturing, sales and marketing. Abbott will book all revenues for HUMIRA, and CAT will receive a royalty fee based on HUMIRA sales.

Abbott's Commitment to Immunology

Abbott is focused on the discovery and development of innovative treatments for immunologic diseases. The Abbott Bioresearch Center, founded in 1989 in Worcester, Mass., United States, is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases. More information about Abbott Immunology and HUMIRA, including full prescribing information, is available on the Web sites http://www.abbottimmunology.com/ and http://www.humira.com/ , or in the United States by calling Abbott Medical Information at 1-800-633-9110.

About Abbott

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 60,000 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 http://www.abbott.com/ .