Conventional disease-modifying antirheumatic drugs such as methotrexate are the mainstay of treatment for rheumatoid arthritis. More recently, biologic agents such as etanercept, infliximab and adalimumab, which act by inhibiting tumour necrosis factor (TNF), have become available. TNF inhibitors have proved to be very effective in patients not responding to conventional disease-modifying antirheumatic drugs. However, about 20% to 40% of patients treated with a TNF inhibitor fail to achieve a 20% improvement in American College of Rheumatology criteria, and more lose response over time (secondary failure or acquired therapeutic resistance) or experience adverse events following treatment with a TNF inhibitor. In this group of patients, therapeutic options were limited until recently and an established treatment approach was to switch from one TNF inhibitor to another. In recent years, therapeutic options in these patients have increased with the introduction of biologic agents with novel mechanisms of action, such as rituximab and abatacept. This review outlines the current evidence in support of the available treatment strategies in patients with an inadequate response or intolerance to an initial TNF inhibitor.
http://arthritis-research.com/content/11/S1/S1Rheumatoid arthritis (RA) is a chronic, progressive, debilitating autoimmune disease that occurs in approximately 1% of adults [1]. Although the disease may develop at any age, RA occurs most commonly in people aged 40 to 70 years. Approximately 2.5 times more women than men are affected [1]. The disease is characterized by chronic inflammation of the synovium, which over time results in damage to the joints, leading to pain and disability. RA is associated with increased mortality, particularly in older women [2,3], and it may reduce life expectancy by 3 to 18 years [4]. Recent studies have demonstrated that a substantial proportion of patients continue to show radiographic progression, even though clinically they are in a state of low disease activity, suggesting that achieving remission should be the ultimate goal [5,6].
Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment for RA. Methotrexate is the most commonly used agent in this class, and it is effective on standard clinical measures of disease activity [7], cost-effective and comparatively well tolerated. The development of biologic agents represented a major advance in the treatment of RA. The targets of biologic agents are interactions between the immune effector cells (T lymphocytes, B lymphocytes and macrophages), which are responsible for inflammation and structural damage in affected joints, and the signalling molecules involved in their activation. The first approved biologic agents for the treatment of RA were inhibitors of tumour necrosis factor (TNF). There are now three agents available in this treatment class: etanercept, infliximab and adalimumab. These agents are very effective at improving the signs and symptoms, and at slowing or preventing structural damage in patients with RA [8-14]. Newer TNF inhibitors are also in clinical development for the treatment of RA and include golimumab [15] and certolizumab pegol [16]. Both of these agents are effective at improving signs and symptoms of disease, and prevention of structural damage has been reported for certolizumab pegol [17,18].
However, anti-TNF agents are not effective in all patients. About 30% of patients treated with a TNF inhibitor failed to achieve an improvement of 20% in American College of Rheumatology criteria (ACR20; primary failure or inefficacy) [11,13,14], and more patients lose efficacy during therapy (secondary failure or acquired therapeutic resistance) [19] or experience adverse events following treatment with a TNF inhibitor.
Very good information Lynn. Good to know, there are options! Thank-you! [QUOTE=waddie]Very good information Lynn. Good to know, there are options! Thank-you! [/QUOTE]