Treatment of rheumatoid arthritis with PEGylated recombinant human soluble tumour necrosis factor receptor type I: a clinical update

• Published in: Annals of the rheumatic diseases 2000-11, Vol.59 (suppl 1), p.i41-i43
• Main Authors: Davis, Mark W, Feige, Ulrich, Bendele, Alison M, Martin, Steven W, Edwards, Carl K
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Bone density; Bones, joints and connective tissue. Antiinflammatory agents; Clinical Trials, Phase II as Topic; Disease; Drug dosages; Gangrene; Humans; Inflammatory diseases; Medical sciences; Molecular weight; PEG sTNF-RI; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Randomized Controlled Trials as Topic; Receptors, Tumor Necrosis Factor - blood; Receptors, Tumor Necrosis Factor - therapeutic use; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins - blood; Recombinant Proteins - therapeutic use; rheumatoid arthritis; Studies; Tumor Necrosis Factor Decoy Receptors; Tumor necrosis factor-TNF
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.59.suppl_1.i41

Preclinical studies to date demonstrate that PEGâ[euro][per thousand]sTNF-RI is efficacious in rodent 2-4 and primate 5 models of acute and chronic inflammatory diseases, includingE coli induced septic shock. 6 PEGâ[euro][per thousand]sTNF-RI has demonstrated efficacy in predictive animal models of RA at doses as low as 0.3 mg/kg every other day. 2 The results of these and other 7-9 preclinical studies indicate that PEGâ[euro][per thousand]sTNF-RI is a promising treatment for chronic inflammatory diseases. The pharmacokinetics of PEGâ[euro][per thousand]sTNF-RI after single SC administration were dose independent in the range of 100 to 1000â[euro][per thousand]μg/kg after single dose administration, and peak plasma concentrations were observed 48 to 96 hours after the dose. 11 The pharmacokinetics were characterised by a slow absorption rate (absorption half life of 25 hours), a limited volume of distribution (130 ml/kg), a low clearance rate (1.1 ml/h/kg), and a long elimination half life (83 hours).