Anti-TNF agents for rheumatoid arthritis

Rheumatoid arthritis (RA) is 3 chronic inflammatory, autoimmune disease wit h 3 prevalence of approximately 1% and an annual incidence of 0.04%. Up to 50% of patients with RA are unable to work 10 years after diagnosis. The di sease is associated with significant morbidity and mortality with associate d medical costs to the UK of between pound 240 M and pound 600 M per year. Non steroidal anti-inflammatory drugs (NSAIDs) have little effect on the un derlying course of RA. but they have some anti-inflammatory and analgesic p roperties. Disease modifying antirheumatic drugs (DMARDs) have been shown t o slow progression of RA and are currently recommended early in the course of treatment of RA which is when disease progression is most rapid. Etanercept and infliximab belong to a new group of parentally administered antitumour necrosis factor (TNF) drugs. Etanercept is licensed in the UK for the treatment of active rheumatoid art hritis in patients who have not responded to other DMARDs and in children w ith polyarticular-course juvenile arthritis who have not responded to or ar e intolerant of methotrexate. ill adults it products significant improvemen ts in all measures of rheumatic disease activity compared to placebo. In pa tients whose disease remains active despite methotrexate treatment. further improvement in control is obtained with the addition of etanercept without an increase in toxicity. In one small trial, etanercept was found to be mo re effective than placebo ill a selected group of children. Infliximab is a monoclonal antibody which is currently licensed in the UK for Crohn's dise ase and, ill combination with methotrexate for the treatment of rheumatoid arthritis in patients with active disease when the response to disease-modi fying drugs, including methotrexate, has been inadequate. Ill clinical tria ls infliximab produced significant improvements ill all measures of rheumat ic disease activity compared with placebo. Infliximab in combination with m ethotrexate was shown to be superior to methotrexate or infliximab alone. There are currently no predictors of 3 good response to anti-TNF drugs and a percentage of patients fail to respond to treatment (25%, to 38%, of etan ercept patients, 21% to 42% of infliximab patients). Infliximab monotherapy induces the production of anti-infliximab antibodies, which may reduce its effectiveness. Adding methotrexate to infliximab therapy may prevent this response. Anti-TNF drugs may affect host defences against infection and malignancy; w hether these agents affect the development and course of malignancies and c hronic infections is unknown and safety and efficacy in patients with immun osuppression or chronic infections has not been investigated. With inflixim ab, upper respiratory tract infections. general infections and those requir ing antimicrobial treatment were more common in patients than placebo. Like wise. upper respirator); tract infections were more common in patients trea ted with etanercept than with placebo. Injection site reactions occur with both infliximab (16%-21%) and etanercept (37%). There are approximately 600 000 patients with RA in the UK, and of these between 2% and 3.5% may have severe disease which has failed to respond to conventional treatment and wh o might be eligible for anti-TNF therapy. If between 50% and 70%, of patien ts treated with anti-TNF drugs respond and continue on long-term treatment then the recurrent annual cost to the NHS could be between pound 48 M and p ound 129 M.