Rheumatoid arthritis - pegsunercept
Although the precise cause of rheumatoid arthritis is unknown, it is an autoimmune condition.
Although the precise cause of rheumatoid arthritis is unknown, it is an autoimmune condition.
Symptoms include joint pain, inflammation and damage to both bone and cartilage. Drug therapies currently rely on non-steroidal anti-inflammatory drugs, which relieve the pain but have no effect on the progression of the disease, and on disease modifying antirheumatic drugs (DMARDs), which do, but their tolerability and efficacy in the long term are limited.
An obvious alternative target would be the immune cascade that results in the disease. Tumour necrosis factor a (TNF-a) is involved in the joint destruction process, as it stimulates resorption of both bone and cartilage, causes inflammation, and suppresses the formation of new bone by suppressing the synthesis of bone collagen.
As a result, Amgen has been investigating agents that act against TNF-a as possible therapies for rheumatoid arthritis, and it has identified pegsunercept as having potential.1 This is a recombinant methionyl p55 monomeric soluble TNF receptor type I that has been linked to polyethylene glycol, a modified form of a previously identified agent that was effective at modifying the disease, but turned out to be immunogenic and unsuitable for administration in the long term.
A Phase II multicentre randomised placebo-controlled trial has been carried out in 194 patients with rheumatoid arthritis.2 The patients were allowed to continue with DMARD therapy, and were given 400 or 800µg/kg of pegsunercept subcutaneously each week for 12 weeks. Those given the higher dose had a significantly higher response rate, and quality of life was improved for patients receiving both doses.
A second Phase II trial in 309 patients with active rheumatoid arthritis has also been carried out.3 In the double-blind randomised placebo-controlled study, subjects were allowed methotrexate but not DMARDs, and dosed with 400, 800 or 1100µg/kg subcutaneously twice a week for 24 weeks. The active at all doses was significantly more effective than placebo.
Pegsunercept's long term safety was investigated in an open label extension study.4 A total of 502 patients who had participated in the aforementioned Phase II trials were given 400 or 800µg/kg once a week, or 300 or 600µg/kg twice a week for an average of seven months. It was found to be well tolerated, and the symptoms of rheumatoid arthritis continued to improve. Phase II trials continue.