Counseling Points - November 2008 - (Page 9)

repetitive disease flares, unacceptable disease activity, such as ongoing disease after 3 months of maximum therapy, or progressive joint damage, the treatment regimen should be changed.12 Biologic DMARDs—Who is a Candidate? Although there are more than 170 possible dual-DMARD or triple-DMARD combinations among the five conventional DMARDs from which to choose, many patients still may have a suboptimal therapeutic response and will require treatment with biologic DMARDs.12 For example, one recent study found that methotrexate montherapy was effective in 1/3 of patients with early RA.15 When additional nonbiologic DMARDS were added to methotrexate (sulfasalazine and leflunomide or sulfasalazine and hydroxychloroquine) a high percentage of patients in each treatment group (64% and 87%, respectively) still failed therapy. However, when a biologic DMARD was added to methotrexate, 71% of patients were treated successfully.15 Treatment with biologic DMARDs has a number of potential advantages over conventional DMARD therapies.11 These agents have novel mechanisms of action to target specific molecules that play pivotal roles in the disease process. Additionally, biologic DMARDs have a rapid onset, induce fewer overall side effects than conventional DMARDs, and have improved dosing schedules.11 Currently there are six biologic DMARDs being used in the clinical management of RA— abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab. Anakinra will not be discussed due to its infrequent use according to the 2008 ACR treatment guidelines.12 ACR treatment recommendations for the use of biologic DMARDS appear in Table 5. pathologic inflammation and the joint destruction associated with RA.11 The three anti-TNF agents available in the United States are adalimumab, etanercept, and infliximab. All of these drugs are efficacious, evidence-based treatments for RA in appropriate patients.12 TFN antagonist therapy has been shown to significantly improve RA course by producing remission and reducing or halting articular destruction in some patients.16 Treatment with biologic DMARDs has a number of potential advantages over conventional DMARD therapies. Individuals with early RA and low or moderate disease activity are not considered candidates for anti-TNF therapy. 12 However, the ACR recommends the use of these agents (interchangeably) in combination with methotrexate in early RA patients who have never received DMARDs with high disease activity present for less than 3 months with features of poor prognosis and an absence of barriers associated with treatment cost and insurance restrictions.12 The ACR also recommends TNF inhibitors in patients with intermediate and longer duration RA with moderate disease activity who have had an inadequate response to methotrexate monotherapy or methotrexate in combination with another DMARD and poor prognostic features and also in patients who have high disease activity regardless of prognosis.12 Although the ACR states that TNF antagonists may be used interchangeably, there are pharmacokinetic differences among the three available agents. Infliximab is a chimeric mouse/human monoclonal antibody and adalimumab is a fully human IgG1 monoclonal antibody, whereas etanercept is a dimeric TNF receptor IgG1 fusion protein. All of the TNF antagonists bind to both soluble and membranebound TNF-α, but etanercept also binds to lymphotoxin.11 Infliximab additionally binds to both monomeric and trimeric TNF forms, which are thought to cause cell lysis via antibody-dependent cell-medicated cytotoxicity or through complement activation.11 Randomized, controlled trials have demonstrated improved physical function and health-related quality of 9 NOVEMBER 2008 TNF Antagonists The recognition of the complex immune cytokine network in RA has revealed new targets for therapeutic intervention, such as tumor necrosis factor (TNF), a pro-inflammatory cytokine produced by macrophages and lymphocytes. As a regulatory protein that is involved in systemic inflammation, TNF is present in large quantities in rheumatoid joints and plays an important role in both the

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Counseling Points - November 2008

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