To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: EULAR: Anakinra (Interleukin-1 Receptor Antagonist) Arrests Joint Destruction, Improves Function In Rheumatoid Arthritis URL: http://www.pslgroup.com/dg/1FE5BA.htm Doctor's Guide June 17, 2001
PRAGUE, CZECH REPUBLIC -- June 17, 2001 -- Amgen today announced that data presented at the European League Against Rheumatism (EULAR) 2001 Annual European Congress of Rheumatology suggest that treatment with the rheumatoid arthritis (RA) therapy anakinra (interleukin-1 receptor antagonist; IL-1ra) can arrest joint destruction in patients with established erosions and improve function, productivity and quality of life for patients with RA. In a double blind, multi-centre, randomized, placebo-controlled study, 472 patients with active RA were randomized to receive 30 mg, 75 mg, or 150 mg daily treatment with anakinra or placebo. After six months, placebo patients were re-randomized in a blinded manner to treatment with one of the anakinra doses. Joint destruction was evaluated by radiographs, using a modified Sharp assessment tool*, and functional status and quality of life were measured by the Health Assessment Questionnaire (HAQ)** and Nottingham Health Profile (NHP), respectively. The first analysis assessed the effect of anakinra on progressive joint damage in patients with baseline erosive disease. Of the 472 patients enrolled in this study, approximately 75 per cent exhibited baseline erosive disease. After 24 weeks of treatment, nearly twice as many anakinra-treated patients with erosive disease demonstrated an arrest of progressive joint damage compared to placebo (31 percent versus 16.7 percent, 150 mg versus placebo, P<0.05) (1). Professor Barry Bresnihan, Professor of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland and lead author, commented, "These results are extremely encouraging. They suggest that patients receiving anakinra who already have baseline erosive disease not only benefit from rapid symptomatic relief, but also the arrest of progressive joint damage is seen after only 20 weeks." Further analyses of this monotherapy trial demonstrated clinically significant benefits to the functional status of RA patients. Following baseline assessment, patients receiving 24 weeks of anakinra experienced a significant improvement in their ability to function, as measured by the HAQ. Mean HAQ scores decreased by an average of 0.24, superior to the mean change in subjects receiving placebo therapy (p=0.0003) (2). This improvement was both statistically significant and clinically meaningful. Additionally, these same anakinra treated patients also displayed an increase of productivity (reduction of lost days of work or domestic activity). These gains occurred rapidly, with over a two-day gain by week 8. Furthermore, by the end of the study, an additional 14 percent of anakinra patients did not miss any work or domestic activities compared to 6 percent for placebo (3). Professor Bresnihan continued, "Rheumatoid arthritis can be an extremely debilitating and painful condition. For people with this disease, maintaining a 'normal' lifestyle, in terms of function and being able to go out to work, are extremely high priorities. Treatment with anakinra has been shown to offer clinically significant benefits in all of these areas." Anakinra also demonstrated health related quality of life benefits, as measured by the Nottingham Health Profile (NHP), in an additional analysis of the same patients, who were not receiving DMARD (disease-modifying anti-rheumatic drug) therapy. The NHP consists of 38 items that assess the physical mobility, pain, energy, sleep, emotional reactions and social isolation. The NHP is scored so the lower scores indicate better health-related quality of life and negative change scores indicate improvements. Patients receiving anakinra for 24 weeks demonstrated statistically significant improvements in their NHP scores, in both physical and psychosocial domains, significantly exceeding those for placebo patients (4). Art Brouwer, Vice-President of Amgen European Operations added, "Amgen is committed to high quality research and development in the field of RA in terms of developing efficacious and unique therapies as well as enhancing quality of life for RA patients. The encouraging data presented this week has clearly demonstrated how this commitment has proved beneficial. We intend to continue our commitment to high quality research and development for anakinra as well as for our other pipeline products." Anakinra is a recombinant form of human IL-1Ra. It competitively binds to IL-1 receptors, interfering with the action of excess IL-1 that RA patients produce, thereby restoring the balance between IL-1 and IL-1Ra. Amgen has filed for regulatory approval of anakinra in the United States, Canada and the European Union and first approvals are expected in the second half of 2001. Amgen also presented data at EULAR this week on PEGylated Recombinant Soluble TNF-Receptor Type I (PEG sTNF-RI), a type I soluble TNF receptor with high-affinity binding to both soluble and membrane bound TNF. PEG sTNF-RI was given weekly for 12 weeks to 194 subjects with RA at doses of 400 or 800 mcg/kg versus placebo. The study assessed both the efficacy and safety of the molecule (5). Efficacy versus placebo was demonstrated by an ACR20 (American College of Rheumatology Responder Index showing >20 percent improvement in both tender and swollen joint counts and in three of five criteria) response rate of 50 percent versus 26 percent (p=0.005) with the 800-mcg/kg-dose group at week 12. Moreover, an increasing ACR20 response rate was seen with increasing doses. Treatment at all doses appeared to be safe and well tolerated. Most notable, however, was the improvement in health-related quality of life (6). To measure this, the SF-36*** was administered at study entry and weeks 4 and 12. Patients using PEG sTNF-RI experienced statistically significant, clinically and socially relevant improvements across a full range of health-related quality of life scales, ranging from the physical to psychosocial. PEG sTNF-R1 is an optimized, monomeric form of a first-generation molecule TNF-binding protein. It was designed to bind to the proinflammatory cytokine Tumor Necrosis Factor and has been modified with a Polyethylene Glycol (PEG) molecule to extend its biological half-life. Phase II studies of PEG sTNF-R1 in RA were initiated in the second quarter of 2001 in the United States, Canada and Europe. Phase I studies of the combination of anakinra and PEG sTNF-R1 in RA were initiated in the first half of 2000. References: (1) B Bresnihan et al. Anakinra arrests joint destruction in patients with RA and established erosions. EULAR, Prague, 2001. (2) Emery et al. Anakinra 0560 Study Group: Improvements in functional status due to anakinra therapy in patients with rheumatoid arthritis who are not using DMARDS. EULAR, Prague, 2001. (3) B Bresnihan et al. Anakinra 0560 Study Group: Anakinra improves productivity as measured by missed work/domestic activity days of patients with RA. EULAR, Prague, 2001. (4) P Emery et al, Anakinra 0560 Study Group: Improvement in health-related quality of life from anakinra therapy in patients with RA not using DMARDS, EULAR, Prague, 2001. (5) M Schiff et al. The efficacy and safety of PEGylated Methionyl Human soluble tumor necrosis factor receptor type I (PEG sTNF-RI) in a randomized, placebo-controlled, double blind, clinical study of patients with rheumatoid arthritis. EULAR, Prague, 2001. (6) J Tesser et al. PEG sTNF-RI improves health-related quality of life in patients with rheumatoid arthritis. EULAR, Prague, 2001. * Modified Sharp assessment tool measures joint destruction based on erosive damage and joint space narrowing of the hands and wrist. Increases in scores signify progressive structural damage. ** Functional status, measured by the Health Assessment Questionnaire (HAQ), an eight-scale tool that assesses a patient's ability to perform standard activities of daily living. Each scale ranges from zero (able to function without any difficulty) to three (unable to function). A weighted sum of the scale scores is the HAQ disability index. A lower score indicates better health-related quality of life. *** The SF-36 consists of 36 items designed to assess physical function, role limitations due to physical problems, body pain, general health, vitality/energy, social function, role limitations due to emotional problems and mental health. The SF-36 is scored from 0 to 100, with higher scores indicating better health-related quality of life. Differences of 3 to 5 points are considered clinically and socially relevant. SOURCE: Amgen --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.