Rheumatoid Arthritis: Management and New Therapies Introduction Rheumatoid Arthritis (RA) is a chronic, systemic disease that affects the synovial joints. Once mechanical damage has occurred, pain and joint deformity often require aids and appliances and, eventually, surgery. Prevalence is approximately 1% worldwide. RA is three times more prevalent in women than men. Review and Discussion of Current Management and Referral Options: High dose of systemic steroids has been used to improve inflammatory synovitis symptoms and decrease progression of joint damage but side effects are unacceptably high. Low dose of systemic steroids may reduce progression of joint damage in early disease and intra-muscular steroids can speed up clinical improvement during initiation of gold therapy or other slow-acting drugs. Other analgesics could be helpful to relieve the symptoms. Monoclonal antibodies for example: infliximab, etanercept, enakinra, adalimumab for RA management. A revolution has occurred in treating RA due to the realisation that the pro-inflammatory cytokine TNF-alpha plays a central role. In the last 10 years several agents have been developed that block this molecule and TNF inhibitors significantly improve symptoms, and reduce disease activity and joint inflammation. Infliximab and etanercept are very effective in reducing the symptoms and signs of RA in patients who fail to respond to DMARDs and both reduce joint swelling, radiological erosions, malaise and fatigue. Recently, NICE (2007) reviewed and endorsed the use and clinical effectiveness of anti-TNF agents, including adalimumab, in active RA after DMARDs therapy failing. Anti-TNF agents have rapid onsets of action of days to weeks. Presentation of disease and management: Data and current situation NICE (2007) hag estimated that 400,000 people are affected in England and Wales and 40% of people with RA will be unable to work within 5 years of diagnosis, and 50% within 10 years. The life expectancy of people with RA is reduced by 5–10 years, 35–50% of this excess risk is accounted for by cardiovascular mortality. The British Society for Rheumatology (BSR) has published standards of care which patients with rheumatoid arthritis should expect to receive. Over time, bone erosion, destruction of cartilage and complete loss of joint integrity can occur. Eventually, multiple-organ systems may be affected. RA is the most common inflammatory arthritis, affecting adult population. Onset usually occurs between 30 and 50 years of age. Symptoms and typical patient complaints Symmetrical joint pain and swelling of small peripheral joints Morning joint stiffness and other diffuse aching. Fatigue, malaise and depression may precede other symptoms by months or weeks. Aetiology and pathophysiology The aetiology of RA is not fully understood. Evidence points to a complex interplay between environmental and genetic factors. Available drug therapies and goals of treatments Joint destruction in rheumatoid arthritis begins within a few weeks of symptom onset; early treatment decreases the rate of disease progression. Therefore, it is imperative to diagnose the disease and initiate treatment as soon as possible. Therapeutic goals include preservation of function and quality of life, minimization of pain and inflammation, joint protection, and control of systemic complications and possible side effects of therapy. Several new drugs recently have become available, including adalimumab, etanercept, leflunomide, infliximab and anakinra. this has not been recommended by NICE (2003) for RA. Pharmacotherapy for RA generally involves a non-steroidal anti-inflammatory drug (NSAID) for control of pain and initiation of a disease-modifying anti-rheumatoid drug (DMARD), corticosteroids, and non-pharmacological modalities also are useful. Patients who do not respond well to a single DMARD may be candidates for combination therapy which has shown better results. TNF is a key regulator of immunity and opportunistic infections, such as tuberculosis. Reactivation and worsening of disease, suppression of bone marrow and a variety of unusual idiosyncratic side effects can occur. BSR advices that patients should be reviewed annually by a hospital specialist or GP with special interest. Surgery Surgery could be considered for some patients who are on maximum tolerated therapy but have uncontrollable pain and/or significant restrictions of joint movement. Reflection In past decades, pharmacological treatment of RA was managed using a pyramid approach. However, different approach are now being experimented, DMARDs and Anti-TNF are initiated quickly to slow disease progression. A recent review mentions some other novel drugs that are in earlier development. These act at various points in the pathogenic cascade, and include some agents targeted at bone destruction rather than the inflammatory process. It is not clear whether the current protocols and referral pathways are being applied appropriately to promote an early diagnosis of RA. Perhaps an enforced coordination between primary and secondary healthcare, especially with a broader multidisciplinary approach and higher level of patient’s education, empowerment and self-management can improve RA management and early detection in order to stop or at least slow the disease progression. ACR 20 Response Rates Sustained in 86% of Combination Group (methotrexate and etanercept) Over 2 Years Conclusion More efficient and safer drugs and different approaches are still needed to treat those patients who do not respond to current therapies and patients should be referred to a specialist rheumatologist as soon as the condition is suspected. Early detection is now possible by laboratory diagnosis. A highly specific antibodies called anticyclic citrullinated peptides occur 10 years before the development of clinical disease. If the test is available to GPs locally it should be performed before referral to secondary care. 86% Etanercept + MTX†‡ (n=231) Etanercept (n=223) MTX (n=228) % of Patients 75% 71% 4 8 12 16 20 24 32 40 48 100 2 52 60 68 76 88 Weeks References -NICE (National Institute for Health and Clinical Excellence) (2007) Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis: Technology appraisal Oct 2007. -Smolen, J. S. (2007) New therapies for treatment of rheumatoid arthritis. The Lancet 2007; 370:1861-1874 -Luqmani, R. et al (2006) British Society for Rheumatology and British Health Professionals in Rheumatology Guideline for the Management of Rheumatoid Arthritis (The first 2 years) -Emery, P et al (2002). Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:290-7. -Klareskog L et al (2004): Annual European Congress of Rheumatology, Berlin, Germany, June 9-12, 2004. -Van Riel PL et al (2006). Efficacy and safety of combination etanercept and methotrexate vs etanercept alone in patients with rheumatoid arthritis with inadequate response to methotrexate.