Drug Topics - March 2009 - (Page 46) Continuing Education RHEUMATOID ARTHRITIS sus 1.5 percent receiving placebo, P=0.003). Findings from this trial suggest that abatacept may be a possible option for controlling RA symptoms, especially in patients inadequately controlled with TNF-alpha antagonists. However, abatacept is not devoid of adverse effects. Patients treated with abatacept have been reported to experience headache, nausea, and infusion reactions. Also, as are other biologic agents, abatacept is associated with an increased risk for infections. In patients who develop serious infections, treatment should be discontinued. For this reason, abatacept should not be given in combination with TNF-alpha antagonists or anakinra. Patients with chronic obstructive pulmonary disease (COPD) have been noted to experience more dyspnea, cough, rhonchi, and COPD exacerbations when treated with abatacept. Cautious use is warranted in this population. Live vaccines should not be administered to patients during treatment with abatacept or for three months after therapy is discontinued. sion reactions, severe mucocutaneous reactions, and tumor lysis syndrome. The risk for fatal infusion reactions is greatest within the first 24 hours following an infusion, and up to 80 percent of cases occur with the first dose. Thus, during all infusions, patients should be closely monitored for the development of urticaria, hypotension, bronchospasms, and myocardial infarction. Rituximab therapy also increases the potential risk for hepatitis B reactivation. Patients have developed a diagnosis of hepatitis B at a median of from four months after therapy initiation to one month after treatment discontinuation. Thus, all patients should be monitored for hepatitis B development while receiving therapy and for a period of time after discontinuation. Screening of all high-risk patients is recommended, and carriers of the virus should be closely monitored throughout therapy. Any patient developing hepatitis B should discontinue therapy with rituximab. Other potential adverse events associated with therapy include bowel obstruction and perforation, renal and cardiac toxicities, hypertension, nausea, and arthralgias. CD20-directed chimeric monoclonal antibody Originally studied for its use in non-Hodgkin’s lymphoma, rituximab has been approved for use in the treatment of rheumatoid arthritis. Rituximab is effective against this condition by depleting immature and mature B cells with CD20 on their surfaces. Ultimately, this reduces the production of cytokines. This agent is given as two 1,000-mg doses on day one and day 15, to be repeated every 15 to 18 months for two to seven years. Most patients experience a B cell depletion for at least six months following a two-dose cycle. An intravenous glucocorticoid such as methylprednisolone 100 mg or its equivalent should be given about 30 minutes prior to infusion along with an antihistamine and acetaminophen to minimize infusion reactions. Initially, the drug is infused at a rate of 50 mg/hour, which can be increased by 50 mg/ hour every 30 minutes to a maximum of 400 mg/hour if the patient does not develop infusion reactions. In the event that an infusion reaction occurs, the rate of therapy should be slowed or interrupted. If the patient tolerated the first infusion, subsequent infusions may occur at 100 mg/hour with increases by 100 mg/hour every 30 minutes to a maximum of 400 mg/hour. Similar to infliximab, rituximab must be given in combination with methotrexate. In a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, rituximab was compared to placebo in patients who had failed TNF-alpha antagonist therapy and were continuing treatment with methotrexate. At 24 weeks, 51 percent of patients receiving rituximab achieved ACR 20 responses (P<0.0001) compared to 18 percent receiving placebo, with similar findings noted for ACR 50 (27 percent versus 5 percent, respectively) and ACR 70 responses (12 percent versus 1 percent, respectively). As are other biologic agents, rituximab therapy is associated with various adverse effects. This drug has quite a few boxed warnings, including an increased risk for fatal infu- Back to Jessica . . . It appears that Jessica’s RA is no longer controlled by methotrexate, leflunomide, and scheduled ibuprofen dosing, all of which are appropriate for a patient with RA. This is evidenced by the presence of painful, swollen, stiff joints, fatigue, and elevated CRP, ESR, and RF levels. The presence of a rheumatoid nodule could be associated with active disease or could be a result of treatment with methotrexate. Therefore, while other nonbiologic agents may be considered, it is a reasonable option to treat with a biologic agent. While infliximab may be effective for treating her symptoms, there is a risk of worsening of her seizures with TNF-alpha antagonist therapy. Thus, consideration may be given to other biologic agents such as anakinra or abatacept. Before starting therapy with a biologic agent, it would be prudent to ensure that Jessica has received all CDC-recommended vaccinations, especially any live immunizations. Also, it may be prudent to ask whether Jessica is planning to become pregnant in the near future. While the biologic agents fall under pregnancy category B or C, there are a lack of safety data for this population of patients. In fact, the manufacturers of some of these biologic agents now have a pregnancy registry for the reporting of any adverse effects. The selection of therapy should be tailored to Jessica’s needs and preferences. Anakinra is associated with daily injections, and abatacept is associated with monthly infusions. In addition, consideration should be given to cost and formulary restrictions, and other health-plan coverage issues. Whatever therapy is chosen, Jessica should be followed closely for response to therapy as well as for the emergence of adverse effects such as infection or injection-site reactions/infusion reactions. It would be prudent for Jessica to be followed by a rheumatologist. W W W.D R U GTO P I C S .C O M 46 DRUG TOPICS March 2009 http://WWW.DRUGTOPICS.COM
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