New Long-Term Humira (adalimumab) Data Show Up to Seven-Year Efficacy with Combination Treatment for Rheumatoid Arthritis

PARIS, June 13, 2008 /PRNewswire-FirstCall/ -- Seven-year rheumatoid arthritis (RA) data from open-label extension studies show that treatment with Abbott's HUMIRA(R) (adalimumab) resulted in clinical remission among long-standing RA patients when used in combination with methotrexate (MTX). The percentage of patients achieving clinical remission continued to increase after two or more years of continuous treatment with combination therapy. These data were presented at the European League Against Rheumatism (EULAR) annual meeting in Paris.

The seven-year HUMIRA data are a combined analysis of open-label extensions of the ARMADA, DE019, STAR, DE005 and DE037 trials. The open-label extension period of these studies assessed the measures of efficacy, remission and change over time in the safety profile in patients with long-standing RA treated for up to seven years with 40mg of HUMIRA every other week plus MTX.

"Rheumatoid arthritis is a chronic, progressive disease with no cure and usually requires long-term management for patients, so it is reassuring that HUMIRA has demonstrated up to seven years of efficacy in patients with this disease," said Michael E. Weinblatt, M.D., Brigham and Women's Hospital, Boston, and lead investigator.

Seven-Year Clinical Data Summary

A total of 1,469 patients with a history of RA who had continued on from randomized, controlled HUMIRA trials were treated with HUMIRA and MTX for greater than or equal to 30 days and up to seven years in open-label extension studies. The average length of exposure to treatment was 47 months.

    The randomized controlled HUMIRA study included:


     *    The ARMADA trial: a Phase III study to evaluate efficacy and safety

          of HUMIRA in patients with moderate to severe RA who had failed at

          least one disease-modifying anti-rheumatic drug (DMARD).

     *    DE019: a Phase III study, which evaluated the efficacy and safety of

          HUMIRA in patients with moderate to severe RA with inadequate

          response to MTX, including assessment of inhibition of radiographic

          progression.

     *    The STAR trial: a Phase III study that evaluated the efficacy and

          safety of HUMIRA when added to a standard treatment regimen for RA

          in patients with inadequate response.

     *    DE005: a Phase I study evaluating the safety and efficacy of HUMIRA

          in combination with methotrexate in methotrexate partial responders.

     *    DE037: a Phase I roll-over study that evaluated the safety,

          pharmacokinetics and early signs of HUMIRA efficacy among RA

          patients in the United States and Japan.



    Efficacy


     *    After six months of therapy, all efficacy measures showed

          significant improvements versus baseline.

     *    At year two, additional improvements were observed in American

          College of Rheumatology (ACR) responses.  ACR responses represent a

          percent improvement in tender joint count, swollen joint count and

          other relevant clinical measures.

     *    Improved response after year one was confirmed by examining

          sustained clinical remission (Disease Activity Score (DAS28) of less

          than 2.6) for at least three consecutive visits; sustained remission

          was achieved in 42 percent of all patients after a mean of 18 +/- 17

          months.  DAS28 is a composite index that includes variables such as

          the number of tender and swollen joints, specific laboratory values

          and other measures of disease activity.



    Safety


     *    The treatment exposure-adjusted rate of serious adverse events

          (SAEs), and serious infections, declined progressively during seven

          years of observation.

     *    Rates and types of SAEs were consistent with randomized controlled

          trials, including the rate of serious infections.  Two patients

          reported tuberculosis, one after three months and another after 13

          months of exposure.


About Rheumatoid Arthritis

Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease where joints are inflamed, which may lead to damage of the joints' interior and the surrounding bone. The joints most commonly affected during the beginning of the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can be affected, but less often. Although there is no cure for RA, people continue to seek treatments that not only alleviate the pain and inflammation but also slow disease progression, thereby inhibiting the joint damage that can hinder patients from performing daily activities. Five million people worldwide are currently living with RA and most of them are between the ages of 25 and 55.

Important Safety Information

Globally, prescribing information varies; refer to the individual country product label for complete information.

Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.

TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the 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 combinations of HUMIRA and anakinra as well as HUMIRA and abatacept is not recommended.

TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.

More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age, gender and race matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of Psoralen Ultra-Violet A (PUVA) treatment, should be examined for the presence of non- melanoma skin cancer prior to and during treatment with HUMIRA.

In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.

The most frequently reported adverse event (greater than or equal to 1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (reported by greater than or equal to >1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia, fatigue (including asthenia and malaise).

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, ankylosing spondylitis (AS) and Crohn's disease in the United States and Europe. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-alpha), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases. To date, HUMIRA has been approved in 75 countries and more than 250,000 people worldwide are currently being treated with HUMIRA. Clinical trials are also under way evaluating the potential of HUMIRA in ulcerative colitis.

In Europe, HUMIRA in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. HUMIRA is also indicated for the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate. In the United States, HUMIRA is also approved for the treatment of juvenile idiopathic arthritis (JIA).

HUMIRA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti- rheumatic drug therapy has been inadequate. HUMIRA has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function.

HUMIRA is indicated for the treatment of adults with severe, active ankylosing spondylitis who have had an inadequate response to conventional therapy.

HUMIRA is indicated for treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with corticosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate.

HUMIRA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.

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.

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 http://www.abbott.com.

CONTACT: International Media, Ilke Arici, +1-847-938-8551, U.S. Media,Raquel Powers, +1-847-935-6563, or Financial, Lawrence Peepo,+1-847-935-6722, all of Abbott

Web site: http://www.abbott.com/

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Posted: June 2008

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