Drug Topics - March 2009 - (Page 43) CONTINUING EDUCATION drawback to using this marker of antibody production is that approximately 30 percent of patients will have a negative finding during the early stages of the disease. Also, it does not accurately measure disease progression and may be positive for other autoimmune disorders. Thus, many healthcare providers will assess anticyclic citrullinated peptide (anti-CCP) antibody levels, which are more specific than RF levels. These levels may be detected as early as three to six months after the emergence of symptoms in 50 percent to 60 percent of patients. Because early treatment is important to prevent joint deformities, anti-CCP antibody assessment represents an important laboratory marker for early disease detection. Other tests such as x-rays and magnetic resonance imaging (MRI) are important for assessment of bony erosions and osteopenia/osteoporosis as well as disease progression. In addition to the clinical presentation and laboratory/ procedural findings, there are criteria for the diagnosis of RA developed by the American College of Rheumatology (ACR) Subcommittee. [See Table 1.] A diagnosis is made when four of the seven criteria described are present. from protein or protein fragments from humans, animals, or microorganisms. Oral administration is not yet possible as the protein derivative is subject to proteolysis and would be quickly inactivated. Thus, these agents are available for subcutaneous or intravenous administration. In addition, these agents are very expensive when only drug cost is considered. (They require less monitoring, so overall, their cost may prove less extreme than it first appears.) Therefore, the cost should be weighed against the potential benefits of therapy. Treatment strategies According to the ACR, early treatment (i.e., within three months of diagnosis) with disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate is important to prevent or control joint damage, prevent loss of function, reduce disease progression, reduce pain, and reduce mortality. Clinical response is often assessed and distinguished from a placebo effect in clinical trials using ACR improvement criteria. Specifically, patients must achieve at least a 20 percent improvement (noted as ACR 20) in tender swollen joints plus at least a 20 percent improvement in three of the following criteria: pain, physician global assessment, patient global assessment, patient-assessed disability, and effects on CRP and ESR levels. Clinical trials have expanded these numbers to include ACR 50, or 50 percent improvement in these measures, ACR 70, or 70 percent improvement in these measures, and ACR 90, or 90 percent improvement in these measures. If the original DMARD selected is inadequate at controlling pain and swelling, several options such as a dosage increase, switching DMARDs, or adding a biologic agent may be considered. Many effective nonbiologic DMARDs exist and are available for treatment. However, at one year, 33 percent of patients who were initially treated with methotrexate will discontinue therapy or require an additional DMARD. Thus, newer, biologic agents that target various components of the overly active immune system have been developed, as a result of technological advances and a better understanding of RA, to provide additional treatment options for the management of RA. Newer, biologic agents for treatment of RA Biologic agents used for the treatment of RA are derived W W W.D R U GTO P I C S .C O M Tumor necrosis factor-alpha antagonists The first class of newer, biologic agents to be approved for RA are the tumor necrosis factor-alpha antagonists, which include etanercept, infliximab, and adalimumab. Targeting the proinflammatory cytokine TNF-alpha causes a reduction in the production of the IL-1 and IL-6 metalloproteinases, among other proinflammatory mediators, resulting in less damage to the joints and cartilage. Also, a cohort study found that patients treated with infliximab and etanercept had a lower risk of developing a first cardiovascular event. These drugs differ in how TNF-alpha is targeted. Therefore, if a patient shows intolerance for the initial drug or fails to achieve a response, another agent may be substituted. The ACR has developed specific recommendations regarding when to use these agents in early, intermediate, and longer stages of RA. These recommendations can be found on the ACR website (www.rheumatology.org). Etanercept is a soluble TNF-receptor fusion protein that binds to both TNF-alpha and TNF-beta to prevent interaction with their receptors. Because it has a half-life after absorption of approximately 103 hours (about four days), etanercept may be given as a 25-mg subcutaneous injection twice weekly or a 50-mg dose once weekly. The injections TABLE 1 American College of Rheumatology Diagnostic Criteria 1. Morning stiffness for at least one hour after movement 2. Swelling and arthritis in three or more joints (i.e. proximal interphalangeal [PIP], metacarpophalangeal [MCP], wrist, elbow, knee, ankle, metatarsophalangeal [MTP]) 3. Arthritis in at least one hand joint (i.e., wrist, MCP PIP) , 4. Symmetrical joint involvement 5. Presence of rheumatoid nodules 6. Positive serum rheumatoid factor (RF) 7. Radiographic changes consistent with RA (i.e., bony erosions, loss of bone density) Criteria 1 through 4 must be present for 6 weeks or more. Four of the seven criteria should be present for a diagnosis. (Adapted from American College of Rheumatology. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002;46:328-346.) March 2009 DRUG TOPICS 43 http://WWW.DRUGTOPICS.COM
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