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RENÉ WESTHOVENS, FRÉDÉRIC HOUSSIAU, JOHAN JOLY, DANIEL E. EVERITT, ESTHER BOUMAN-THIO, YAOWEI ZHU, DEBORAH SISCO, BART van HARTINGSVELDT, MARY ANN MASCELLI, MARTIN A. GRAHAM, and PATRICK DUREZ ABSTRACT. Objective. To assess safety, clinical response, and pharmacokinetics of subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of infliximab [including experimental SC doses following administration of commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid arthritis (RA) refractory to methotrexate. Methods. In this randomized, open-label, 3-stage design, 43 subjects were enrolled in 7 dose groups. In Stage I, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 mg/kg. In Stage II, 21 subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections); 3 mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions) followed by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks (3 injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3 injections). Results. No treatment-related serious adverse events were observed, and there were no serious injection site reactions. A low-titer infliximab antibody response was detected in 27% of subjects receiving single SC doses, 5% receiving multiple SC doses, and 43% receiving IM doses. SC administration yielded roughly dose-proportional increases in Cmax and AUC. American College of Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2 weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses, and 80.0% receiving SC doses every 4 weeks. Conclusion. SC and IM treatment with this experimental infliximab formulation was well tolerated and was associated with a favorable ACR response. (First Release April 1 2006; J Rheumatol 2006;33:847–53) Key Indexing Terms: RHEUMATOID ARTHRITIS
From the Rheumatology Department, University Hospitals KU Leuven, Leuven, Belgium; Rheumatology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium; Johnson & Johnson Pharmaceutical Research and Development, LLC, Springhouse, Pennsylvania, USA; Centocor, Inc., Malvern, Pennsylvania, USA; Centocor, BV, Leiden, The Netherlands; and PKPD Inc., Philadelphia, Pennsylvania, USA. Supported by Centocor, Inc. R. Westhovens, MD, PhD, Professor, Rheumatology Department, KU Leuven; F. Houssiau, MD, PhD, Professor, Rheumatology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; J. Joly, RN, Department of Rheumatology, KU Leuven; D.E. Everitt, MD; E. Bouman-Thio, MD; Y. Zhu, PhD; D. Sisco, BS; B. van Hartingsveldt, MSc; M.A. Mascelli, PhD; M.A. Graham, PhD; P. Durez, MD, Chef de Clinique Adjoint, Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain. Address reprint requests to Dr. R. Westhovens, Rheumatology Department, UZ Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. E-mail: rene.westhovens@uz.kuleuven.ac.be Accepted for publication December 6, 2005.
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