Counseling Points - March 2008 - (Page 9)

any available DMARD and requires no routine laboratory monitoring.2,3 GI upset is the most common side effect; thus, it is generally recommended that the medication be taken with a meal.23 Although rare, ocular toxicity is the most adverse side effect; hence, a baseline ophthalmologic examination and follow-ups every 12 months are recommended while using this drug.3,24 Sulfasalazine (Azulfidine®) Sulfasalazine is a synthetic agent that is derived from salicylic acid (the active ingredient in aspirin), and an antibiotic, sulfapyridine. Sulfasalazine can be used alone or in conjunction with other DMARDs.19,25 It is unknown precisely how sulfasalazine works on RA, but the mechanism of action is thought to be related in part to how it promotes adenosine release to mediate anti-inflammatory effects.3 A typical dose of sulfasalazine is 1 gram to 1.5 grams orally twice a day.19,25 The dose may be initiated at 500 mg twice daily and titrated as tolerated. Sulfasalazine works more quickly than hydroxychloroquine. The usual time to treatment effect is 6 weeks to 3 months, but benefits have been reported as early as 1 month.19 The drug may cause hypersensitivity and allergic reactions in patients who have experienced sulfa medication toxicity.25 Mild GI complaints, such as nausea and abdominal discomfort, can be improved if sulfasalazine is administered with meals.25 Both sulfasalazine and hydroxychloroquine are generally used to treat early, mild cases of RA.2,3 Leflunomide (Arava®) A number of clinical trials have established that leflunomide may be used as an alternative to methotrexate, specifically for patients who cannot tolerate methotrexate or for those who experience an inadequate response.3 The chemical structure of the drug differs from other DMARDs currently used to treat RA.26 Although the mechanism of action by which leflunomide works has not been fully explained, it is believed to be related to its ability to suppress the enzyme dihydroorotate dehydrogenase (DHODH).27 DHODH inhibition results in beneficial immunosuppressant and antiproliferative effects in diseases such as RA.27 Because leflunomide has an exceptionally long half-life (15 to 18 days), a loading dose of 100 mg per day for 3 days may be used to provide steady-state concentrations more rapidly.28 A dose of 20 mg of leflunomide daily is recommended as maintenance therapy, but may be reduced to 10 mg daily if the drug is not well tolerated.19,28 The disease-modifying effects of leflunomide usu9 ally can be seen in 4 to 8 weeks.19,28 Leflunomide has been associated with liver function abnormalities. Other side effects include mild diarrhea, nausea, and alopecia. Additionally, the drug is a potent teratogen; therefore, women of childbearing age and their partners must practice effective birth control and, before attempting conception, “washout” with a prescribed course of cholestyramine.28 Biologic agents have novel mechanisms of action to target specific molecules that play pivotal roles in the disease process. Biologic DMARDs In recent years, there has been an enormous amount of research evaluating therapy with biological DMARDs in RA. Treatment with these newer drugs has a number of potential advantages over conventional DMARD therapies. For example, biologic agents have novel mechanisms of action to target specific molecules that play pivotal roles in the disease process. Some of these drugs attack inflammatory cytokines, such as tumor necrosis-alfa (TNF-α), interleukin-1 (IL-1), and IL-6, which have been linked to the inflammatory and erosive processes of RA.10,19,28 Other agents modulate T cells or target B cells that express specific proteins involved in the RA disease process.10,19,28 Furthermore, biologic DMARDs also have a more rapid onset of action than conventional DMARDs and improved dosing schedules that range from administration every other week to as long as every other month.10,19,28 Although biologics overall induce fewer toxic side effects than conventional DMARDs, they are still associated with adverse events such as infection (sometimes severe), skin irritation, and leukopenia.2, 10,19,28 Tumor Necrosis Factor (TNF) Inhibitors TNF-α is a pro-inflammatory cytokine produced by macrophages and lymphocytes. As a regulatory protein that is involved in systemic inflammation, it is present in large quantities in rheumatoid joints and plays an important role in both the pathologic inflammation and the joint destruction associated with RA.28 There are currently three FDA-approved TNF antagonists: adalimumab, etanercept, and infliximab. These drugs are similar to one another in the way they decrease signs and symptoms of RA, inhibit radiographic damage, and improve function and quality of life.28 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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