Humira Stops Joint Damage For 5 Years in Early RA

Data Suggest Moderate to Severe Early RA Patients Achieve Greatest Results With Initial Combination Use of Humira Plus Methotrexate

ABBOTT PARK, Ill., October 29, 2008 – New data show half of patients with moderate to severe early rheumatoid arthritis showed no progression of joint damage at five years. These results were seen in patients who initially received HUMIRA? (adalimumab) in combination with methotrexate (MTX) for two years and continued on HUMIRA for an additional three years in an open-label extension study. These results were presented this week at the American College of Rheumatology annual meeting in San Francisco.

Five-year results of the PREMIER study found that patients with early rheumatoid arthritis (RA) achieved the best results with an initial combination of HUMIRA and methotrexate. Early RA patients were defined as those who had been diagnosed with the disease for less than three years. The patients who were started on combination therapy of HUMIRA with MTX when they entered the PREMIER trial had less progression of joint damage at year five than patients who started on either HUMIRA or MTX therapy alone. Patients who received the combination of HUMIRA plus MTX had the smallest average increase in modified total Sharp score (mTSS), a measurement used to determine joint damage. The increase in mTSS at year five in the combination group was 2.9 compared with 9.7 in the MTX-alone group and 8.7 in the HUMIRA-alone group.

"Early and aggressive treatment of moderate to severe rheumatoid arthritis can help prevent the progression of joint damage caused by this disease," said Desiree van der Heijde, M.D., of the Leiden University Medical Center in the Netherlands and lead author. "These data suggest that initial combined therapy with HUMIRA plus methotrexate for two years is better than either monotherapy alone in inhibiting radiographic progression for up to five years."

About the Study

PREMIER was a randomized, double-blind study for two years, followed by a three-year open-label extension. The PREMIER study evaluated the ability of HUMIRA to inhibit radiographic progression for up to five years in patients with moderate to severe early RA. In the blinded portion of PREMIER, 799 patients received either HUMIRA plus MTX, HUMIRA alone, or MTX alone for two years.

Patients who completed the two-year double-blind period of the study and chose to enroll in the extension study received open-label HUMIRA 40 mg every other week for an additional three years. 354 patients completed five years of therapy and had x-rays available for evaluation. Of these, 124 initially received Humira plus MTX, 115 received MTX alone, and 115 received HUMIRA alone when they started the two-year PREMIER trial.

X-rays were evaluated for progression of joint damage as measured by change in mTSS from baseline. More than half of the patients initially receiving combination therapy showed no further joint damage (mTSS increase of no more than 0.5) at five years.

"We continue to study HUMIRA to determine the benefit to patients of starting treatment early and remaining on therapy long-term in order to help inhibit the progression of joint damage," said Eugene Sun, M.D., vice president, Global Pharmaceutical Research and Development at Abbott.

Important Safety Information

Serious infections, sepsis, tuberculosis (TB) and opportunistic infections, including fatalities, have been reported with the use of TNF-blocking agents, including HUMIRA. Many of these serious infections have occurred in patients also taking other immunosuppressive agents that in addition to their underlying disease could predispose them to infections. Infections have also been reported in patients receiving HUMIRA alone.

Treatment with HUMIRA should not be initiated in patients with active infections. TNF-blocking agents, including HUMIRA, have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA. The combination of HUMIRA and anakinra is not recommended and patients using HUMIRA should not receive live vaccines.

More cases of malignancies have been observed among patients receiving TNF blockers, including HUMIRA, compared to control patients in clinical trials. These malignancies, other than lymphoma and non-melanoma skin cancer, were similar in type and number to what would be expected in the general population. There was an approximately three-fold higher rate of lymphoma in combined controlled and uncontrolled open label portions of HUMIRA clinical trials. The potential role of TNF- blocking therapy in the development of malignancies is not known. TNF-blocking agents, including HUMIRA, have been associated in rare cases with demyelinating disease and severe allergic reactions. Infrequent reports of serious blood disorders have been reported with TNF-blocking agents.

Worsening congestive heart failure (CHF) has been observed with TNF-blocking agents, including HUMIRA, and new onset CHF has been reported with TNF-blocking agents. Treatment with HUMIRA may result in the formation of autoantibodies and rarely, in development of a lupus-like syndrome.

In the placebo-controlled clinical studies of adult patients with rheumatoid arthritis, the most frequent adverse reactions 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.

In HUMIRA clinical trials for ankylosing spondylitis, psoriatic arthritis, Crohn’s disease and plaque psoriasis, the safety profile for adult patients treated with HUMIRA was similar to the safety profile seen in adult patients with rheumatoid arthritis. In the placebo-controlled clinical trials in plaque psoriasis, the incidence of arthralgia was 3 percent in HUMIRA-treated patients versus 1 percent in controls.

In general, adverse reactions in pediatric patients were similar in frequency and type to those seen in adult patients. Severe adverse reactions reported in the clinical trial in juvenile idiopathic arthritis (JIA) included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia and appendicitis. Serious infections were observed in 4 percent of patients within approximately 2 years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. Safety of HUMIRA in pediatric patients for uses other than JIA has not been established.

As with any treatment program, the benefits and risks of HUMIRA should be carefully considered before initiating therapy.

About HUMIRA

HUMIRA is approved by the FDA for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural joint damage, and improving physical function in adult patients with moderately to severely active RA.

HUMIRA is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in adult patients with psoriatic arthritis. HUMIRA is also indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. HUMIRA is indicated for reducing the signs and symptoms and inducing and maintaining clinical remission in adults with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. HUMIRA is indicated as a treatment to reduce signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients four years of age and older.

HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-α), an inflammatory protein that, when produced in excess, plays a key role in the inflammatory responses of some autoimmune diseases.

To date, HUMIRA has been approved in 77 countries and more than 310,000 patients worldwide are currently being treated with HUMIRA. Clinical trials are currently under way evaluating the potential of HUMIRA in other immune-mediated diseases.

Abbott's Commitment to Immunology

Abbott is focused on the discovery and development of innovative treatments for immunologic diseases.

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.

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 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.

Edelman Health 312-233-1223 caroline.landree@edelman.com

Posted: October 2008

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