Abstract
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.
Highlights
Rheumatoid arthritis (RA) is a chronic, progressive, debilitating autoimmune disease that occurs in approximately 1% of adults [1]
Despite the therapeutic advance that tumour necrosis factor (TNF) inhibitors have brought to RA treatment, more than 50% of patients fail to achieve at least an ACR50 response, and more lose response over time or experience adverse events after treatment with TNF inhibitors
Observational studies have shown that some patients who have had an inadequate response to an initial TNF inhibitor do show an improvement in disease activity when switched to another TNF inhibitor
Summary
Rheumatoid arthritis (RA) is a chronic, progressive, debilitating autoimmune disease that occurs in approximately 1% of adults [1]. The proportion of patients who achieved a minimum clinically important difference (defined as an improvement in HAQ of ≤0.22 units) was higher for switchers (36%) than for stayers (31%) or stoppers (22%; P < 0.01 versus switchers) These data suggest that switching to a second TNF inhibitor is more beneficial than discontinuing treatment and receiving no biologic therapy during the subsequent 12 months, the majority of patients who switched did not experience a clinically significant improvement regarding functionality. A recently reported observational study [54] indicated that, in a population of patients with inadequate response to one or more TNF inhibitors, rituximab may be more effective at controlling disease activity than switching to an alternative TNF inhibitor (Figure 9). Further investigation in larger numbers of patients over time is warranted
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