Additional ENBREL Five-Year Data Support Long-term Efficacy and Tolerability in Rheumatoid Arthritis
THOUSAND OAKS, Calif. and COLLEGEVILLE, Pa., Oct. 24 -- More than one third (37 percent) of rheumatoid arthritis (RA) patients treated with Enbrel(R) (etanercept) plus methotrexate combination therapy achieved clinical remission of their disease at one year as measured by the Disease Activity Score (DAS) criteria. In addition, 80 percent of combination-treated patients experienced no progression of joint damage and a majority (51 percent) of patients reported significant improvement in functionality at one year. Results from the ENBREL TEMPO, (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study were presented at the American College of Rheumatology's (ACR) Annual Scientific Meeting in Orlando, Fla.
"It is very exciting as a physician to see such a sizeable proportion of combination therapy RA patients in this study achieve clinical remission and, for the first time, statistically significant, credible evidence of negative progression scores," said Desiree van der Heijde, M.D., professor of rheumatology, University of Maastricht in the Netherlands. "The outstanding results of the ENBREL TEMPO study underscore the importance of aggressive treatment of RA and give new insight to combination treatment of the disease."
At one year, 37 percent of patients taking combination therapy of ENBREL and methotrexate (n=212) achieved clinical remission, as assessed by the Disease Activity Score (DAS). In comparison, 18 percent of patients treated with ENBREL alone (n=212) and 14 percent of patients treated with methotrexate alone (n=212) achieved clinical remission during the same time period. Clinical remission is defined as a DAS score of <1.6. DAS scores measure tender and swollen joints, erythrocyte sedimentation rate (ESR), an inflammatory marker found in the blood, and overall disease activity.
"This is the first time any TNF inhibitor in combination with methotrexate has demonstrated the ability to help this many patients achieve clinical remission as measured by DAS criteria-a major goal of RA therapy," said Willard Dere, M.D., vice president of clinical development for Amgen.
Additionally, 80 percent of combination-treated patients experienced no progression of joint damage (unit change of TSS<0.5) at one year as assessed by the van der Heijde modified Total Sharp Score (TSS), an x-ray measurement of changes in joint damage. In comparison, 68 percent and 57 percent of ENBREL monotherapy and methotrexate monotherapy-treated patients, respectively, had no progression of joint damage at one year. Combination therapy patients also achieved a mean negative Total Sharp Score (-0.5 unit mean change, 95 percent confidence interval of -1.00 to -0.07). ENBREL monotherapy patients experienced significantly less progression of joint damage compared with methotrexate monotherapy patients, with a 0.5 unit mean change from baseline at one year in TSS compared with a 2.8 unit mean change.
At one year, a substantial percentage of patients experienced an improvement in RA symptoms. In the ENBREL and methotrexate combination group, 85 percent of patients achieved ACR 20, 69 percent achieved ACR 50 and 43 percent of patients achieved ACR 70. ACR scores are a composite measure of improvement in RA symptoms, including joint swelling and tenderness, pain, level of disability, overall self and physician assessment, and an objective marker of inflammation, such as ESR.
Patients also completed a Health Assessment Questionnaire (HAQ), which measures functionality. Fifty-one percent of combination therapy patients reported an improvement in HAQ scores of greater than or equal to 1, indicating a significant improvement in functionality.
The ENBREL TEMPO study randomized 682 patients with RA, of which 642 were included in radiographic analysis for a period of one year to receive ENBREL (25 mg twice weekly), methotrexate (up to 20 mg once weekly) or ENBREL (25 mg twice weekly) plus methotrexate twice weekly. Patients in the ENBREL TEMPO trial had active RA and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD) other than methotrexate. The primary radiographic endpoint was the change from baseline in van der Heijde-modified TSS at one year. Secondary radiographic endpoints included the changes in total erosions, changes in total joint space narrowing, number of eroded joints and non-progression (TSS change less than or equal to 0.5 or TSS change less than or equal to 3.0 or progression greater than the smallest detectable difference).
Proven Efficacy and Tolerability Over a Five-Year Period
Results from a long-term follow up study of patients enrolled in the original ENBREL studies, some of which lead to FDA approval of ENBREL five years ago, further support the continued efficacy and tolerability of ENBREL. This study followed more than 2,000 patients taking ENBREL. A subset of these patients was followed for as long as five years. Thirty percent of those patients experienced no tender joints, 23 percent had no swollen joints and 16 percent had a Health Assessment Questionnaire (HAQ) score of zero, which indicates no disability, at the five-year mark (n=329). Additionally, the rate of infections was comparable to that of control groups in controlled clinical trials.
"ENBREL has been enhancing the lives of individuals with RA for more than five years, reducing disability and helping them to return to more normal lives," says Victoria Kusiak, M.D., vice president of global medical affairs and North American medical director of Wyeth Pharmaceuticals. "These data reinforce the proven tolerability and sustained efficacy of ENBREL in patients with RA, and we are committed to exploring its use to help patients across a number of TNF-activated disorders."
More than two million Americans suffer from RA, which causes stiffness, swelling and limitation in the motion and function of multiple joints. If left untreated, or improperly treated, patients can become disabled from irreversible joint damage caused by the disease, limiting their ability to function.
ENBREL is the only fully human TNF receptor approved to reduce signs and symptoms, improve physical function, and inhibit the progression of structural damage in patients with moderately to severely active rheumatoid arthritis (RA), and to reduce the signs and symptoms and inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. ENBREL is the only biologic therapy approved for first-line treatment of RA patients, and can be used alone or in combination with methotrexate. It is approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). It is also the first biologic approved to treat the signs and symptoms in patients with active ankylosing spondylitis (AS).
ENBREL has been used by more than 200,000 patients worldwide across indications since becoming commercially available nearly five years ago.
ENBREL acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory process of RA, JRA, psoriatic arthritis and AS. The binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, the following have been reported in patients using ENBREL:
* Serious Infections - Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes - Some serious infections were fatal - Rare cases of tuberculosis * What to do/Not do - Do not start ENBREL if you have an infection or are allergic to ENBREL or its components - Tell your doctor if you are prone to infection - Stop ENBREL if a serious infection occurs - Contact your doctor if you have questions about ENBREL or develop an infection * Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes. - Tell your doctor if you have ever had any of these disorders or if you develop them after starting ENBREL. * Rare reports of serious blood disorders (some fatal) - Contact your doctor immediately if you develop symptoms such as persistent fever, bruising, bleeding, or paleness * In medical studies of all TNF-inhibitors, a higher rate of lymphoma (a type of cancer) was seen compared to the general population, however, the risk of lymphoma may be up to several fold higher in RA patients. The role of TNF-inhibitors in the development of lymphoma is unknown. * The incidence of other cancers has not increased with extended exposure to ENBREL and is similar to the expected rate. * ENBREL can also cause injection site reactions. * In a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults. - The kinds of infections reported were generally mild and similar to those usually seen in children - Other serious adverse reactions were reported rarely, including serious infections (2 percent) and depression/personality disorder (1 percent)
Amgen and Wyeth Pharmaceuticals, a division of Wyeth, market ENBREL in North America. Wyeth markets ENBREL outside of North America. Immunex Corporation, a wholly owned subsidiary of Amgen, manufactures ENBREL. Additional information about ENBREL, including full Prescribing Information, can be found on the Web site sponsored by the companies at www.enbrel.com or by calling toll free 888-4ENBREL (888-436-2735).
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