- Studies are Among Longest Open-Label Trials in Patients with Rheumatoid Arthritis Treated with an Anti-TNF

BERLIN, June 6, 2012 /PRNewswire/ -- Abbott (NYSE: ABT) today announced results from two long-term, open-label studies, which evaluated the results of HUMIRA® (adalimumab) treatment for up to 10 years in patients with long-standing, moderate-to-severe rheumatoid arthritis (RA). These 10-year HUMIRA studies, DE019 and DE020, are among the longest, open-label trials in RA. Results presented at the European League Against Rheumatism (EULAR) 2012 Congress in Berlin, Germany, include information on clinical response, radiographic inhibition and physical function data in patients with long-standing RA.

In both studies, patients were assessed for improvements in signs and symptoms of the disease, such as joint pain, swelling and stiffness, as well as physical function and achievement of clinical remission. Following up to 10 years of HUMIRA therapy, patients in the studies continued to maintain improvements in disease activity. In both DE019 and DE020, a DAS28 (CRP) <2.6, a measure of clinical remission, was observed in more than half of patients who continued on HUMIRA for up to 10 years (59.6 percent and 57.2 percent, respectively). A DAS28 score of <2.6 as a measure of clinical remission is supported by both EULAR and the American College of Rheumatology (ACR).

DE019 also assessed the ability of HUMIRA to inhibit radiographic progression. Patients who completed 10 years of treatment and also had X-rays available at baseline and year 10 demonstrated an average change of 2.8 in modified total Sharp score (mTSS), a measure of radiographic inhibition. In this study, patients who were initially treated with HUMIRA plus methotrexate (MTX) for the first year had less radiographic progression (measured as mean change in mTSS) at year 10 compared with patients who initially received placebo plus MTX. This result was driven by the change in mTSS during the one year randomized controlled trial.

"Managing RA is more than just treating the signs and symptoms, but also inhibiting joint damage, and improving physical function," said Dr. Edward Keystone, Professor of Medicine, University of Toronto, Canada. "The results of these long-term studies add to the vast arsenal of evidence that rheumatologists can reference when treating their patients with RA, a disease with irreversible effects."

Abbott's global clinical trial database for HUMIRA is extensive and includes more than 14,000 RA patients representing more than 23,000 patient years of exposure to the medication.

"Many patients with RA are not diagnosed early in the disease process and then may not be treated as quickly as they should, which can result in long-term, and sometimes irreversible, effects of the disease," said John Medich, Ph.D., divisional vice president, Clinical Development, Immunology, Abbott. "These long-term results on clinical response and radiographic inhibition provide additional data about the use of HUMIRA in long-standing RA and further demonstrate Abbott's continued commitment to improving the standards of care for patients with the disease."

Clinical outcomes were assessed by Disease Activity Score 28 (DAS28), which is a composite index that includes variables such as the number of tender and swollen joints and either erythrocyte sedimentation rate or C-reactive protein (CRP), both of which are measures of inflammation.

About DE019

DE019 was a Phase 3, randomized, controlled trial in which patients with long-standing RA and an inadequate response to MTX were randomized to one year of HUMIRA 40 mg every other week (ADA-40), HUMIRA 20 mg weekly (ADA-20) or placebo (PBO) injections; all received concomitant MTX. The 52-week controlled portion of the trial demonstrated the clinical and radiographic superiority of HUMIRA plus MTX over placebo plus MTX. Of the 619 patients initially randomized, a total of 202 patients (32.6 percent) continued on open-label HUMIRA plus MTX through year 10. This post-hoc analysis evaluated the radiographic data available at baseline and year 10 for patients who had data available for both time periods.

Clinical and functional outcomes were assessed using the DAS28 and the Health Assessment Questionnaire Disability Index (HAQ-DI), which is a measure of a patient's physical function. Radiographic damage was assessed at baseline and years one, eight and 10 using the modified total Sharp score (mTSS), which records both bone and cartilage damage (joint erosion score and joint space narrowing score, respectively) on X-ray.

After ten years in the study, patients had a mean DAS28 (CRP) of 2.6, mean HAQ-DI of 0.7 and a mean change in mTSS of 2.8. DAS28 (CRP) <2.6 was observed in more than half of patients who continued on HUMIRA for up to 10 years (59.6 percent). In the DE019 study, no new safety signals were identified following up to 10 years of HUMIRA exposure.

About DE020

DE020 was a long-term, open-label, follow-up trial enrolling patients from four previous studies (including the ARMADA and STAR studies, as well as two smaller studies) in the early development program of HUMIRA. All four studies included patients with active RA and an inadequate response to MTX and/or other disease-modifying antirheumatic drugs (DMARDs). Patients could receive supplemental DMARD therapy at the investigator's discretion after inclusion in DE020. A total of 846 patients were enrolled in this follow-up study.

Clinical and functional responses were assessed as the percentage of patients observed to achieve ACR criteria 20/50/70 responses, DAS28 <3.2 (a measure of low disease activity), DAS28 <2.6 and HAQ-DI <0.5 at year 10. ACR response criteria measure the percent improvement in tender and swollen joints, as well as patient and physician global assessment, pain, disability and inflammatory markers.

A total of 286 patients (33.8 percent) completed 10 years of treatment with HUMIRA. DAS28 (CRP) <2.6 was observed in more than half of patients (57.2 percent) at year 10. A composite of both DAS28 (CRP) <3.2 and HAQ-DI <0.5 was observed in more than one-third (37.3 percent) of patients at year 10. At baseline, the patient population showed a mean DAS28 score of 5.7, indicating high disease activity.

The mean DAS28 score at year 10 was 2.6. At baseline, the patient population had a mean HAQ-DI score of 1.4 (+/-0.6). At year 10, average HAQ-DI scores were observed to be 0.8 (+/-0.7). The following data were also observed at year 10:

• 78.6 percent of patients achieved at least 20 percent improvement in the ACR criteria (ACR20)
• 55.5 percent achieved at least 50 percent improvement in the ACR criteria (ACR50)
• 32.8 percent achieved at least 70 percent improvement in the ACR criteria (ACR70)
• 71.2 percent achieved a Disease Activity Score 28 [DAS28 (CRP) <3.2]
• 42.4 percent achieved a Health Assessment Questionnaire Disability Index (HAQ-DI) <0.5

No new safety signals were identified in this study following more than 10 years of HUMIRA exposure and rates of adverse events (AE) were consistent with the known safety profile of HUMIRA.

About HUMIRA® (adalimumab)

Uses
HUMIRA (adalimumab) is a prescription medicine used alone, with methotrexate, or with certain other medicines to reduce the signs and symptoms of moderate to severe rheumatoid arthritis in adults. It may prevent future damage to bones and joints and may help with the ability to perform daily activities.

Important Safety Information
HUMIRA is a TNF blocker medicine that affects the immune system and can lower the ability to fight infections. Serious infections have happened in people taking HUMIRA. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections. People should be tested for TB before HUMIRA use and monitored for signs and symptoms of TB during therapy. People at risk of TB may be treated with medicine for TB.

Treatment with HUMIRA should not be started in a person with an active infection, unless approved by a doctor. HUMIRA should be stopped if a person develops a serious infection.

People should tell their doctor if they live in or have been to a region where certain fungal infections are common, have had TB, hepatitis B, are prone to infections, or have symptoms such as fever, fatigue, cough, or sores.

For people taking TNF blockers, including HUMIRA, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers including HUMIRA, the chance of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life-threatening if treated.

Other possible serious side effects with HUMIRA include hepatitis B infection in carriers of the virus, allergic reactions, nervous system problems, blood problems, certain immune reactions, including a lupus-like syndrome, liver problems, and new or worsening heart failure or psoriasis. The use of HUMIRA with anakinra or abatacept is not recommended. People using HUMIRA should not receive live vaccines.

Common side effects of HUMIRA include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.

HUMIRA is given by injection under the skin.

The benefits and risks of HUMIRA should be carefully considered before starting therapy.

This is not a complete list of the safety information for HUMIRA. For additional important safety information, please click for the Full Prescribing Information and Medication Guide.

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 approximately 91,000 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.

SOURCE Abbott