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Intravenous Human Recombinant Tumor Necrosis Factor Receptor p55-Fc IgG1 Fusion Protein, Ro 45-2081 (Lenercept): Results of a Dose-Finding Study in Rheumatoid Arthritis
DANIEL E. FURST, MICHAEL WEISMAN, HAROLD E. PAULUS, KENNETH BULPITT, MICHAEL WEINBLATT, RICHARD POLISSON, MICHEL ZAUG, JOHANNES KNEER, PHILIPPE VAN DER AUWERA, RANDALL M. STEVENS, and THE RHEUMATOLOGY STUDY GROUP 825
ABSTRACT.
Methods. In a double-blind, placebo-controlled, parallel-group, multicenter trial, adult patients with long-standing active RA stabilized on conventional therapy were randomly assigned to receive 3 IV infusions, one every 4 weeks, of one of the following: (a) placebo, (b) lenercept 0.01 mg/kg (maximum 1 mg), (c) lenercept 0.05 mg/kg (maximum 5 mg), (d) lenercept 0.2 mg/kg (maximum 20 mg), or (e) lenercept 0.5 mg/kg (maximum 50 mg). The material utilized in the study had a lower relative bioavailability [lower area under the time-concentration curve (AUC) per mg infused] than that used in a recent similar trial. Efficacy variables included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain. Results. Patients treated with lenercept exhibited improvement as early as one day after the first IV infusion. The treatment benefit, however, was modest, maximized by 2 weeks and then diminished or vanished as non-neutralizing anti-lenercept antibody concentrations increased. The majority of adverse experiences were mild or moderate and not considered related to study drug. Conclusion. Our results showed that lenercept administered by IV infusion every 4 weeks is well tolerated, but only transiently effective in patients with long-standing RA, likely due to both the low relative bioavailability of the material used in the study and the formation of non-neutralizing anti-lenercept antibodies. (J Rheumatol 2003;30:2123-6) Key Indexing Terms:
TUMOR NECROSIS FACTOR-a RECEPTOR
From the Virginia Mason Research Center, Seattle, Washington; University of California, San Diego; University of California, Los Angeles, California; Brigham and Women's Hospital, Boston; Massachusetts General Hospital, Boston, Massachusetts; F. Hoffmann-LaRoche, Nutley, New Jersey, USA; and Basel, Switzerland. Supported by F. Hoffmann-LaRoche. D.E. Furst, MD, Virginia Mason Research Center (current address University of California, Los Angeles); M. Weisman, MD, University of California, San Diego (current address Cedars Sinai Medical Center, Los Angeles); H. Paulus, MD; K. Bulpitt, MD, University of California, Los Angeles; M. Weinblatt, MD, Brigham and Women's Hospital; R. Polisson, MD, Massachusetts General Hospital; M. Zaug, Pharm D, MSc; J. Kneer, PhD; P. Van der Auwera, MD, F. Hoffmann-LaRoche, Basel; R. Stevens, MD, F. Hoffmann-LaRoche, Nutley. Address reprint requests to Dr. D.E. Furst, University of California, Los Angeles, 1000 Veteran Ave, Los Angeles, California, USA, 90095-1670. E-mail: defurst@mednet.ucla.edu Submitted February 19, 2002; revision accepted March 19, 2003. |