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

A recombinant form of the high aYnity, natural inhibitor of tumour necrosis factor á (TNFá) is currently under development for the treatment of rheumatoid arthritis (RA). This molecule is referred to as recombinant-methionyl soluble TNF-type I receptor (r-metHu-sTNF-RI or sTNF-RI). Recombinant sTNF-RI is an Eschericia coli derived recombinant, truncated, monomeric form of the 4-domain soluble TNFtype I receptor. For optimal delivery, a high molecular weight (30 kDa) PEG molecule is attached at the N-terminus (met 1) position to form the molecule intended for clinical investigations (PEG r-metHu-sTNF-RI or PEG sTNF-RI). PEG sTNF-RI, with an approximate molecular weight of 42 kDa, has been designed for long term chronic subcutaneous (SC) administration for the treatment of RA. Preclinical studies to date demonstrate that PEG sTNF-RI is eYcacious in rodent and primate models of acute and chronic inflammatory diseases, including E coli induced septic shock. PEG sTNF-RI has demonstrated eYcacy in predictive animal models of RA at doses as low as 0.3 mg/kg every other day. The results of these and other preclinical studies indicate that PEG sTNF-RI is a promising treatment for chronic inflammatory diseases.