DMARDs

Disease-modifying Anti-rheumatic Drugs (DMARDs)... 

The treatment approach to RA has undergone a major evolutionary change in recent years with a move away from predominantly symptomatic treatment approaches towards much earlier intervention with diseasemodifying anti-rheumatic drug (DMARD) therapy and... 

DL-CFU Dendritic cell/Langerhans cell colony forming DLE Discoid lupus erythematosus DMARD Disease-modifying antirheumatic drug... 

Table 54-3 highlights dosing, safety, monitoring, and patient counseling information for the common DMARDs and BRMs. 

FIGURE 54-2. Outl ine of the management of rheumatoid arthritis. (From Guidelines for the management of rheumatoid arthritis 2002 update. Arthritis Rheum 2002 46(2) 328-346, with permission.) DMARD, disease-modifying antirheumatic drug NSAID, nonsteroidal antiinflammatory drug ... 

TABLE 54-3. FDA-Approved DMARDs and BRMs for Treatment of Rheumatoid Arthritis1 2 7 15 21 42... 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

Hydroxychloroquine may cause retinal toxicity, and patients must have their eyes examined at least annually to detect this abnormality. It is not associated with renal, hepatic, or bone marrow suppression and therefore may be an acceptable treatment option for patients with contraindications to other DMARDs because of their toxicities. 

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

Adalimumab is a recombinant human IgGl monoclonal antibody specific for human TNF.27 Adalimumab binds to soluble and bound TNF-a. Patients may experience symptomatic relief in as early as 1 week. Adalimumab can be administered in combination with methotrexate or other DMARDs.2... 

Anakinra is a recombinant form of human IL-1 receptor antagonist. Anakinra inhibits the activity of IL-1 by binding to it and preventing cell signaling.28 Patients must administer a subcutaneous injection every day, which may be less desirable than other treatment options. Anakinra may be used in combination with other DMARDs in patients not responding to or unable to tolerate DMARDs or TNF antagonists.21 Anakinra should not be used in combination with TNF antagonists due to the increased risk of infection.21... 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

Assess the patient s response to initiation of DMARD therapy after allowing adequate time for the medication to achieve its therapeutic effect. 

DMARD disease-modifying antirheumatic drug ESR erythrocyte sedimentation rate... 

A disease-modifying antirheumatic drug (DMARD) should be started within the first 3 months of symptom onset (Fig. 4-1). DMARDs should be used in all patients except those with limited disease. Early use of DMARDs results in a more favorable outcome and can reduce mortality. 

DMARDs that are less frequently used include azathioprine, penicillamine, gold salts (including auranofin), minocycline, cyclosporine, and... 

Combination therapy with two or more DMARDs may be effective when single-DMARD treatment is unsuccessful. Combinations that are particularly effective include (1) MTX plus cyclosporine, and (2) MTX plus sulfasalazine and hydroxychloroquine. 

Nonsteroidal antiinflammatory drugs (NSAIDs) and/or corticosteroids may be used for symptomatic relief if needed. They provide relatively rapid improvement compared with DMARDs, which may take weeks to months before benefit is seen. However, NSAIDs have no impact on disease progression, and corticosteroids have the potential for long-term complications. 

See Tables 4-2 and 4-3 for usual dosages and monitoring parameters for DMARDs and NSAIDs used in RA. 

NSAIDs act primarily by inhibiting prostaglandin synthesis, which is only a small portion of the inflammatory cascade. They possess both analgesic and antiinflammatory properties and reduce stiffness but do not slow disease progression or prevent bony erosions or joint deformity. They should seldom be used as monotherapy for RA instead, they should be viewed as adjuncts to DMARD treatment. Common NSAID dosage regimens are shown in Table 4-4. 

Hydroxychloroquine lacks the myelosuppressive, hepatic, and renal tox-icities seen with some other DMARDs, which simplifies monitoring. Its onset may be delayed for up to 6 weeks, but the drug should not be considered a therapeutic failure until after 6 months of therapy with no... 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Oral corticosteroids (e.g., prednisone, methylprednisolone) can be used to control pain and synovitis while DMARDs are taking effect ( bridging therapy ). This is often used in patients with debilitating symptoms when DMARD therapy is initiated. 

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