Treatment of Rheumatoid Arthritis with a Recombinant Human Tumor Necrosis Factor Receptor (p75)–Fc Fusion Protein

Abstract

In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.

Remaining Pain in Early Rheumatoid Arthritis Patients Treated With Methotrexate

“…Thus, inflammatory actions on nerve endings, including nociceptive fibers, may result in long‐term sensitization, which contributes to chronic pain conditions. Proinflammatory cytokines like tumor necrosis factor (TNF) and interleukin 6 (IL‐6) are both of specific importance in RA pathogenesis, and specific cytokine blockade has been shown beneficial 22, 23. Both TNF and IL‐6 also affect pain thresholds in experimental arthritis 24, 25, as well as long‐term sensitization of joint nociceptors 26.…”

Electro-gene therapy of collagen-induced arthritis by using an expression plasmid for the soluble p75 tumor necrosis factor receptor-Fc fusion protein

“…37 Randomized, double-blind, placebo-controlled trials showed that human p75 sTNFR:Fc fusion protein treatment yielded significant clinical benefits, with minimal toxicity, in patients with RA who had inadequate responses to other disease-modifying drugs. 17 Soluble cytokine receptors may have a distinct advantage over other TNF-neutralizing agents, such as monoclonal antibodies, in terms of immunogenicity. Indeed, no antibodies against sTNFR:Fc were detected in clinical studies involving patients with RA and normal volunteers.…”

“…Indeed, no antibodies against sTNFR:Fc were detected in clinical studies involving patients with RA and normal volunteers. 17,38 However, due to the chronic characteristics of autoimmune arthritis, subcutaneous injection of 25 mg sTNFR:Fc twice weekly is required to obtain a significant clinical benefit.…”

“…14,15 Several experimental and clinical studies demonstrated that the p75 TNFR:Fc fusion protein was effective in RA while the p55 TNFR:Fc fusion protein worked, but to a lesser extent. [16][17][18] Effective control of autoimmune arthritis requires prolonged neutralization of proinflammatory mediators, and gene therapy offers several potentially unique advantages over previous protein therapies. With the recent advances in gene therapy, the TNFR gene has been delivered by retrovirus and adenovirus-based vectors intraarticularly or systemically to achieve anti-inflammatory effects with varying degrees of success.…”

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

“…Indeed, the aim of medical treatment of RA patients has shifted from the short-term improvement of the quality of life (QOL) through pain relief to the long-term improvement of QOL by the prevention of joint damage and improved mortality. Tumor necrosis factor (TNF) is considered to be a major cytokine involved in RA pathogenesis, and anti-TNF therapy using monoclonal antibodies or fusion proteins was the first anti-cytokine therapy to be developed for RA [4–6]. Anti-TNF therapy has achieved great success in suppressing rheumatoid inflammation and preventing the progression of joint damage in RA patients [7–9], thereby confirming that TNF indeed appears to be critically involved in the pathogenesis of RA synovitis.…”