RA is the most common of all chronic inflammatory joint diseases, affecting 0.5-1% of the population in the industrialised world. Its typical symptoms are joint pain, stiffness, and swelling due to synovial inflammation and effusion.
Professor Josef Smolen, Division of Rheumatology, Medical University of Vienna, Austria and colleagues did a comprehensive study of the three new drugs – rituximab, abatacept and tocilizumab – and their effects as sole therapies or working in conjunction with existing treatments. They explore the pathogenesis of RA and the various routes for targeting treatments, including new therapeutic strategies, and also provide a comprehensive overview on ways to assess treatment response.
The authors say: “The enormous consequences for the individual and for health-care and socioeconomic systems can only be prevented by effective treatments.”
Traditional treatments for RA include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs). Only DMARDs, and to some extent glucocorticoids, can impede or stop the inflammatory and destructive disease processes. Methotrexate is the most widely used DMARD and is a cornerstone of most RA treatment regimens.
Of the three new drugs, rituximab and abatacept have been approved for RA treatment, while the third, tocilizumab, is in phase III trials. Rituximab targets the CD20 antigen in certain cells, and leads to a reduction in the CD20 cell count. Trials of rituximab showed it reduced RA symptoms by more than 50% for more than a third of patients.
Abatacept works by interfering in the T-cell activation response, viewed as vital in the mechanism of RA. A trial combining abatacept at 10mg per kg bodyweight for patients with their existing methotrexate treatment also found a reduction of RA symptoms of around 50% in some 40% of patients. This effect was much more pronounced than in patients given placebo instead of abatacept.
Tocilizumab targets interleukin-6, which is known to activate many cell populations. As with abatacept, combining tocilizumab with methotrexate reduced RA symptoms (in a phase II trial) by 50% in more than 40% of the patients.
Side effects vary between the drugs. Infusion reactions occurred in 30-35% of rituximab patients on first infusion, and rates of serious infections were higher with rituximab patients than those given placebo. Patients taking abatacept had higher incidence of headache, dizziness and serious infections than placebo. And some patients taking tocilizumab experienced headache and skin eruptions, stomatitis, fever, and increases in cholesterol levels and liver enzymes compared to placebo in phase II trials.
The authors conclude by saying all three new drugs diminish signs and symptoms of RA and improve physical function and health status, and retard progression of joint damage – thus expanding the range of treatments to fight RA.
But they conclude: “The many patients who obtain insufficient responses to established and novel treatments indicate the need to search for further therapies and treatment principles to increase response rates and to achieve high frequencies of remission or even cure in rheumatoid arthritis. The prospects are here.”
Tony Kirby | alfa
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