Rheumatoid Arthritis: Garrison L

Garrison L, McDonnell ND. · Immunex Corporation, Seattle, WA 98101, USA. · Ann Rheum Dis. · Pubmed #10577976 links to  free full text

Abstract: Tumour necrosis factor (TNF) plays a central part in the pathophysiology of rheumatoid arthritis (RA). TNF initiates signal transduction by interacting with surface bound TNF receptors. Soluble tumour necrosis factor receptors (sTNFRs) act as natural inhibitors of TNF activity. Etanercept, recombinant p75 sTNFR:Fc fusion protein, has received approval from the US Food and Drug Administration for patients with RA and juvenile RA (JRA) who have failed treatment with at least one other drug. Etanercept has demonstrated excellent safety and efficacy in large scale, randomised, double blind, placebo controlled trials of patients with RA and JRA who are refractory to other disease modifying anti-rheumatic drugs. The therapeutic effects mediated by etanercept are rapid and sustained. Combining etanercept with methotrexate was found to be safe and more effective than treatment with methotrexate alone in the treatment of RA. These clinical findings demonstrate that etanercept can result in symptomatic improvement in patients with RA and JRA. Etanercept is an important new addition to the treatment of these diseases.

Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, Weaver AL, Keystone EC, Furst DE, Mease PJ, Ruderman EM, Horwitz DA, Arkfeld DG, Garrison L, Burge DJ, Blosch CM, Lange ML, McDonnell ND, Weinblatt ME. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 35294-7201, USA. · Ann Intern Med. · Pubmed #10075615 links to  free full text

Abstract: BACKGROUND: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. OBJECTIVE: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. SETTING: 13 North American centers. PATIENTS: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. INTERVENTION: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months. MEASUREMENTS: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. RESULTS: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. CONCLUSIONS: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.