Orlando, Florida, October 24, 2003 — New data show that Abbott Laboratories’ HUMIRA (adalimumab) exhibits sustained response for up to five years in adult patients with active rheumatoid arthritis (RA). The data, presented this week at the American College of Rheumatology (ACR) annual meeting show that HUMIRA, taken alone or in combination with methotrexate (MTX), was effective in reducing signs and symptoms of RA over a five-year period, and was well tolerated.
“With a progressive, debilitating disease such as RA, having a therapy like HUMIRA that offers long-term efficacy and safety is an important option,” said Ferdinand C. Breedveld, M.D., professor, Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, and lead investigator on the study.
HUMIRA with MTX Effective and Well Tolerated at Five Years
An open-label extension study was designed to evaluate the long-term efficacy and safety of HUMIRA in patients with active RA taking methotrexate. Sixty-eight percent (n=36) of patients who entered this study remained on HUMIRA for five years.
Trial participants received standard doses of MTX (16 mg/week) and HUMIRA (1 mg/kg) administered by intravenous injection or subcutaneous injection (under the skin). Frequency of administration varied from once a week to every four weeks, with the majority of patients receiving HUMIRA every other week. After 2.5 years, all patients began receiving 40 mg every other week
Overall results at five years show a sustained reduction in signs and symptoms of RA as measured by ACR 20, 50, and 70 scores, which represent percentage improvements in tender and swollen joint counts and other clinical measures. At year five, 77 percent of patients receiving HUMIRA achieved an ACR 20 response, 46 percent achieved an ACR 50 response, and nearly 1 in 4 (22 percent) achieved an ACR 70 response, which represents the closest clinical measure to remission of RA signs and symptoms.
During the initial double-blind study period, frequency and type of adverse events were comparable between both HUMIRA treatment arms and placebo. The rate of adverse events was stable during the long-term follow-up period
“These data are particularly important because RA is a progressive, life-long disease and patients need a treatment option, such as HUMIRA, with sustained effectiveness in treating signs and symptoms and slowing disease progression,” said Jim Lefkowith, M.D., divisional vice president, Immunology Development, Abbott Laboratories.
HUMIRA Shows Sustained Benefit as Monotherapy at Five Years
A second study examined the sustained effectiveness and safety of HUMIRA primarily as monotherapy in RA patients whose mean duration of disease was 11 years and mean number of prior disease modifying antirheumatic drugs (DMARDs) was 3.8. In all, 794 patients who completed treatment with HUMIRA in previous studies were enrolled in a long-term continuation trial, receiving 40 mg of HUMIRA every other week (EOW). Patients on MTX in the initial study (10 percent) were allowed to remain on therapy
Of the original 794 patients, 48 had received HUMIRA for five years and demonstrated sustained improvement in signs and symptoms as measured by ACR scores. Sixty-seven percent achieved an ACR 20 response, 40 percent achieved an ACR 50 response and 17 percent achieved an ACR 70 response, which represents the closest clinical measure to remission of RA signs and symptoms. The median swollen joint count was 3.5, and the median tender joint count was 4.0, which represented an improvement from baseline.
HUMIRA as monotherapy over five years provided sustained benefit and was well tolerated in patients with established RA (greater than two years), with the spectrum of adverse events similar to those seen in placebo-controlled trials. Rate of serious infections was 0.037 per patient-year
Of patients who remained on HUMIRA for five years, 16 percent had no tender joints, 14 percent had no swollen joints, five percent had a HAQ score of zero, and five percent had a DAS28<2.
“Patients with established RA who have failed other DMARDS represent an enormous treatment challenge,” said Michael Schiff, M.D., director of clinical research, Denver Arthritis Clinic. “These findings are encouraging and suggest using HUMIRA as monotherapy is effective and well tolerated particularly in this patient group.”
RA is a chronic autoimmune disease that affects more than five million people worldwide, with women accounting for three out of four cases. RA causes pain, swelling and stiffness in the joints of hands, feet and wrists, and often leads to the destruction of joints. Unlike osteoarthritis, the “wear and tear” joint condition and most common form of arthritis, RA is an autoimmune disease where joints are inflamed, often resulting in eventual destruction of the joint’s interior and erosion of the surrounding bone. The long-term prognosis for RA patients can be poor, and many patients face disability and premature death.
Quality of life is seriously affected as RA progresses. Many people with RA experience fatigue, which can be extreme and limit normal activity. Sufferers also endure pain that can interfere with daily function, missed workdays, and feelings of helplessness and depression
Important Safety Information
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Cases of tuberculosis (TB), frequently disseminated or extra pulmonary at clinical presentation, 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 on concomitant immunosuppressive therapy that in addition to their underlying disease could predispose them to infections. Other invasive opportunistic fungal infections have also been observed in patients treated with TNF-blocking agents, including HUMIRA.
TNF-blocking agents, including HUMIRA, have been associated in rare cases with exacerbation of demyelinating disease. The most frequent adverse events seen in the placebo-controlled clinical trials (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.
HUMIRA is the first human monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for reducing the signs and symptoms and inhibiting the progression of structural damage in adults with moderately to severely active rheumatoid arthritis (RA) who have had insufficient response to one or more traditional disease modifying antirheumatic drugs (DMARDs). HUMIRA can be used alone or in combination with methotrexate (MTX) or other DMARDs. HUMIRA was created using phage display technology, resulting in an antibody with human-derived heavy and light chain variable regions and human IgG1:K constant regions.
On September 10, 2003, the European Commission granted marketing authorization to HUMIRA for the treatment of adult rheumatoid arthritis (RA). With E.U. marketing authorization, HUMIRA became the first 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. HUMIRA is indicated for the treatment of moderate to severe active RA in adult patients when the response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate.
On October 1, 2003, HUMIRA submitted a supplemental Biologics Licensing Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval for the use of HUMIRA to improve physical function in patients with moderately to severely active rheumatoid arthritis
Clinical trials are also 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, like RA. The Abbott Bioresearch Center, founded in 1989 in Worcester, Massachusetts, U.S., is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases.
As part of its commitment to the research and treatment of immunological diseases, Abbott developed the Abbott Scholar Award, which provides funding to researchers in the early stages of their careers to promote career development and encourage continued research in rheumatology.
Additionally, Abbott and the ACR Research and Education Foundation are collaborating to develop new opportunities for medical residents interested in the field of rheumatology. This collaboration – supported by a $4.5 million endowment from Abbott, the largest one-time gift that the Foundation has received to date – is designed to ensure the continued recruitment of rheumatologists and rheumatology health professionals for years to come.
More information about Abbott Immunology and HUMIRA, including full prescribing information, is available on the Web sites, www.abbottimmunology.com and www.HUMIRA.com, or in the United States by calling Abbott Medical Information at 1-800-633-9110.
Patients interested in more information about RA can visit the Web site, www.RA.com.
Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals, nutritionals, and medical products, including devices and diagnostics. The company employs more than 70,000 people and markets its products in more than 130 countries. In 2002, the company’s sales were $17.7 billion.