Tumour necrosis factor inhibitors: risks and benefits in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and can, if left untreated, result in significant disability and early death. It is also associated with large direct and indirect costs to the individual and to society. Early and aggressive disease modifying anti-rheumatic drug (DMARD) treatment of patients at risk of erosive disease has improved the outcome in the majority, but not all, RA patients. Tumour necrosis factor (TNF) appears to be a key mediator of the inflammatory and destructive process in RA, and consequently inhibitors of TNF action have been tested in randomized controlled trials in patients with RA. The results of these studies have suggested that TNF inhibitors are potent DMARD particularly when combined with methotrexate. They appear well tolerated with the commonest adverse events related to their parenteral route of administration, and the serious but rare side-effects being various infections, notably tuberculosis, multiple sclerosis, and worsening of cardiac failure. Treatment costs are high and range from $15 000 to $25 000 per patient per year. Etanercept, adalimumab and infliximab have recently been subsidised under the Pharmaceutical Benefits Scheme in Australia for patients with severe DMARD-resistant RA. The availability of TNF inhibitors in RA represents a significant advance in the treatment of patients with severe RA.