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

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).