Counseling Points - March 2008 - (Page 11)

signal imparted by proteins CD80 and CD86, which is necessary for full T-cell activation. Abatacept is intravenously administered over 30 minutes at a fixed dose of approximately 10 mg/kg. It is initially given at baseline, 2 weeks, 4 weeks, and then once per month.28,34 Response to abatacept is typically seen within 3 months.29 Results from clinical trials have demonstrated that when used in combination with methotrexate, abatacept produced significant improvements in RA symptoms, physical functioning, and quality of life.33 Furthermore, patients with initial responses continued to exhibit sustained symptom and functional improvements over 12 months.33 The most frequently reported adverse effects of abatacept are headache, upper respiratory infections, nasopharyngitis, and nausea.35 Infections are also increased, and range from mild to severe.35 Due to an increased risk of infection and neoplasms, the drug should not be administered concomitantly with TNF antagonists, anakinra, or other biologic DMARDs. In clinical trials, the frequency of adverse events increased when abatacept was given to patients with chronic obstructive pulmonary disorder (COPD). Therefore, extreme caution should be undertaken when treating RA patients with COPD and they should be closely monitored for worsening of respiratory status.35 B-Cell Depletion: Rituximab (Rituxan®) Like abatacept, rituximab is a newer compound used to treat RA that is refractory to TNF antagonist therapy. Used in combination with methotrexate, rituximab is indicated to reduce signs and symptoms of RA in patients with moderately to severely active disease.36-38 Recent research indicates that B cells initiate and contribute to the inflammatory process of RA by disrupting antigen presentation by T cells and promoting the expression of proinflammatory cytokines and autoantibodies.36-38 CD20 is an antigen that is present on B cells and is thought to play an important role in B-cell activation and proliferation. Rituximab is a chimeric monoclonal antibody that binds complement and induces antibody-dependent cellular cytotoxicity, effectively depleting CD20expressing B-cells.36-38 Results from clinical trials have documented that rituximab is effective in both improving the signs and symptoms of RA and in slowing joint deterioration.36,37 Moreover, beneficial effects of this agent may last 6 months to 2 years following a single course of treatment.36,37 In one pivotal study, patients taking rituximab achieved significantly 11 higher ACR scores at 24 weeks, compared with placebo controls. Additionally, rituximab had a statistically significant effect on slowing structural damage at 56 weeks, relative to placebo.36,37,39 There are many effective treatments available to help alleviate symptoms and slow or halt the damaging effects of RA. A course of rituximab is intravenously administered in two 1,000-mg doses given 2 weeks apart and each infusion takes about 3 to 4 hours.38 Common side effects include headache, nausea, and upper respiratory tract infection.38 Although rare, cases of hepatitis B reactivation have been reported with rituximab.38 Additionally, infusion reactions may occur with the agent, including hives, itching, swelling, difficulty breathing, fever, chills, and changes in blood pressure, and usually develop within 24 hours after the first infusion.33 To reduce the incidence of these reactions, pretreatment with corticosteroids, acetaminophen, and an antihistamine is recommended.38 IL-1 Receptor Antagonist: Anakinra (Kineret™) IL-1, a cytokine produced by macrophages and other specialized cells in the synovium, contributes to the inflammatory effects of RA. IL-1 is typically downregulated by the naturally occurring IL-1 receptor antagonist, which competes for binding to the IL-receptor type 1.28 It is thought that people with RA have an imbalance or deficiency in ILreceptor antagonists, or an overabundance of IL-1, which contributes to the inflammatory effects of the disease.28 Anakinra is a recombinant form of human IL-1 receptor antagonist and targets IL-1 receptor type 1.40 It competitively inhibits IL-1 from binding to the IL-1 receptor type 1, thus retarding the biologic inflammatory activity of the cytokine.40 In clinical trials, the drug has been demonstrated to significantly slow the rate of radiographic progression of RA.40 Response to anakinra treatment usually occurs between 2 to 4 weeks.29 Because of its short half-life, the recommended dosage of anakinra is 100 mg per day injected subcutaneously.19,28,40 Skin irritation (sometimes severe) at the injection site is the most adverse event associated with use of anakinra and occurs in approximately two-thirds of patients.28,40 Treatment with the drug increases infections, and serious infections have occurred in 2% of patients taking anakinra compared with 1% of subjects taking placebo.28,40 Also, the use of anakinra in combination with TNF inhibitors MARCH 2008

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Counseling Points - March 2008 Welcome Pharmacological and Nonpharmacological Treatment of Rheumatoid Arthritis

Counseling Points - March 2008

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