- Reduction of disease activity, prevention of further joint damage and preservation of physical function were the three goals evaluated
ABBOTT PARK, Ill., Nov. 12, 2012 /PRNewswire/ -- Abbott today announced results from a post-hoc analysis of HUMIRA® (adalimumab) data in early and long-standing moderate-to-severe rheumatoid arthritis (RA) patients from three randomized, controlled trials—DE019, OPTIMA and PREMIER. The analysis evaluated the simultaneous achievement of three key treatment goals: low disease activity, normal physical function and the absence of radiographic progression at one year. These results are being presented at the American College of Rheumatology Annual Scientific Meeting (ACR) in Washington, D.C.
In the analysis, low disease activity was measured by the Disease Activity Score 28 based on C reactive protein [DAS28 (CRP)], less than 3.2; normal function was measured by the Health Assessment Questionnaire for RA Disability Index [HAQ-DI], less than 0.5; and the absence of radiographic progression was demonstrated by a change in modified Total Sharp Score [mTSS], less than or equal to 0.5 at one year.
For long-standing RA patients in the DE019 trial, 19 percent (40/207) of patients taking HUMIRA plus methotrexate (MTX) simultaneously achieved all three key treatment goals at one year, versus 5 percent (10/200) of placebo plus MTX-treated patients in the study. DE019 enrolled patients with long-standing moderate-to-severe RA (mean=11 years) and an inadequate response to MTX.
For early RA patients in the OPTIMA trial – those who were given open label HUMIRA plus MTX following inadequate response to 26 weeks of MTX monotherapy – 29 percent (102/348) of patients simultaneously achieved all three key treatment goals at one year. This rate was comparable to what was observed in the PREMIER trial with MTX-naïve early RA patients who were treated with HUMIRA plus MTX (32 percent; 87/268). OPTIMA and PREMIER enrolled early moderate-to-severe RA (mean=0.4 and 0.7 years, respectively) and MTX-naïve patients.
According to treatment guidelines from the ACR and the European League Against Rheumatism (EULAR), the primary target of RA treatment should be clinical remission, defined as the absence of signs and symptoms of significant inflammatory disease activity. For patients with long-standing disease, ACR and EULAR recommend low disease activity as an appropriate alternative measure.
"In recent years, we have been discussing the need for a broader approach to treatment—such as in addition to measuring disease activity, measuring structural changes and functional impairment—which may help physicians and patients mitigate further irreversible effects of the disease," said Dr. Edward Keystone, Professor of Medicine, University of Toronto, Canada. "This analysis evaluates whether or not this is a realistic treatment goal for RA patients, and sheds light on HUMIRA's potential to help patients simultaneously achieve all three key treatment goals. It also supports that the response rates are likely to be higher in patients diagnosed and treated earlier."
All studies in this analysis–DE019, OPTIMA and PREMIER–included a comparison of the use of HUMIRA plus MTX versus placebo plus MTX. The results are based on a post-hoc analysis and are hypothesis-generating only.
"Advances in the last decade offer new treatment options to better manage RA, including reducing signs and symptoms, improving physical function and inhibiting progression of further joint damage," said John R. Medich, Ph.D., divisional vice president, Immunology Clinical Development, Global Pharmaceutical Research and Development, Abbott. "We believe that the potential effects of RA need to be addressed in a comprehensive manner that addresses not only symptom improvement but also other important treatment goals. Through 15 years of clinical experience and ongoing HUMIRA studies, Abbott is committed to this effort."
About Rheumatoid Arthritis
RA is a chronic inflammatory disease that can start in any joint of the body, but most commonly begins in the smaller joints in the fingers, hands and wrists. Unlike osteoarthritis, the "wear and tear" arthritis and most common form of arthritis, RA is an autoimmune disease and occurs when the body's immune system malfunctions, attacking healthy joints. Major symptoms include joint pain, stiffness and swelling. RA affects approximately 1.3 million people in the U.S. and 1 percent of the adult population worldwide.
DE019 was a Phase 3, randomized, placebo-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 injections; all received concomitant MTX. The primary endpoints were ACR 20 response rate at 6 months, change in HAQ and change in mTSS at week 52. Results of this trial demonstrated the clinical, functional and radiographic superiority of HUMIRA plus MTX over placebo plus MTX.
OPTIMA was a multicenter, randomized, double-blind, 78-week two-period study that enrolled 1,032 MTX-naïve patients age 18 or older with early (less than one year) moderate to severe RA. In period 1, patients were randomized to receive the combination of HUMIRA 40 mg every other week (eow) and MTX or placebo and MTX for 26 weeks. Patients in the combination therapy arm who achieved the target (defined as LDAS, DAS28<3.2) at week 22 and 26 were blindly re-randomized to receive either MTX alone (treatment arm 1) or continued combination therapy (treatment arm 2) in period 2. Patients in the initial placebo plus MTX group who achieved the target at weeks 22 and 26 continued to receive MTX monotherapy (treatment arm 4) in a blinded fashion in period 2. Patients failing to achieve the target at weeks 22 and 26 received open-label combination therapy regardless of initial treatment assignment (treatment arms 3 and 5).
The primary endpoint of the study was a composite response of LDAS (DAS28<3.2) and no radiographic progression (change in mTSS < or = to 0.5) at week 78 in patients who continued the combination of HUMIRA and MTX versus those who continued on MTX monotherapy (arms 2 and 4). Significantly more patients who achieved the initial target response in period 1 and who continued on HUMIRA + MTX achieved the composite outcome of a LDAS and no radiographic progression at week 78 compared with those that achieved the initial target with placebo and MTX in period 1 and continued to receive placebo + MTX.
PREMIER was a Phase 3, randomized, controlled trial in MTX-naïve patients with early moderate to severe RA. Patients received MTX, HUMIRA 40 mg eow or HUMIRA 40 mg eow plus MTX for two years of blinded treatment. The co-primary endpoints were ACR 50 response and mean change from baseline in mTSS at week 52 for the HUMIRA + MTX combination therapy arm versus the MTX monotherapy. Results of this trial demonstrated the radiographic, clinical and functional superiority of initial combination therapy over the individual monotherapies.
About HUMIRA® (adalimumab)
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 lifethreatening 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.
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