Rheum for Improvement

Rheumatoid arthritis (RA) is one of the most common forms of arthritis, with a prevalence worldwide of about one per cent. It is a chronic, inflammatory, multisystem, autoimmune disorder that affects the joints in a polyarticular manner. RA can be distinguished from other forms of arthritis in that it is characterised by inflammation and soft-tissue swelling of many joints at the same time (polyarthritis). As the disease progresses, it gradually affects all joints in the body and the inflammatory activity leads to erosion and destruction of the joint surface, which impairs their range of movement and leads to deformity. Some relief from pain can be achieved through use of the affected joints, meaning that stiffness and joint pain is at its most acute first thing in the morning.

Examination of the synovium in RA patients indicated that cytokines are important in mediating the inflammatory process. In particular, tumour necrosis factor alpha (TNF-α) has emerged as a proinflammatory cytokine with a key role to play (1). TNF-α inhibition is therefore a logical strategy in the treatment of RA.

ANTI-TNF ANTIBODY THERAPEUTICS

This has led to the development of monoclonal antibodies such as Remicade (Infliximab, Centocor Inc) (2) and Humira (Adalibumab, Abbott Laboratories) (3) and the p75 TNF-α receptor – immunoglobulin Fc fusion protein, Enbrel (Etanercept, Amgen/Wyeth) (4) as diseasemodifying treatments for RA. Blockade of TNF-α using each of these treatments reduces the signs and symptoms of inflammation and also appears to retard the destruction of joints through disease progression.

However, treatment with these anti-TNF-α therapies is expensive – in the region of about ˆ7,000-10,000 a year per patient – which limits their availability in most countries to only certain patients. Part of the reason for this high cost is the fact that these antibody therapeutics are needed in substantial quantities to achieve their therapeutic effects. Administering such large amounts of antibody to a patient carries its own risks. An additional factor is the cost of manufacturing, as each of these RA treatments is produced in costly rate-limiting mammalian cell-culture. This in turn means that production cannot be easily accommodated to large increases in demand.