General Approach to Treatment

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The clinician must evaluate patient-specific factors and select appropriate treatment to maximize the care of an individual patient. Thirty percent of all patients with RA have radiographic evidence of erosions at the time of diagnosis; therefore, all patients should be treated early and aggressively to reduce disease progression and to prevent joint erosions.1 Aggressive treatment is defined as one or more disease-modifying antirheumatic drugs (DMARDs) at effective doses. Delaying treatment will result in more destructive disease that is very difficult to delay or reverse to preserve joint function. Specialty care by a rheumatologist may reduce the likelihood of disease progression and joint damage.1

O It is imperative that the initiation of one or more DMARDs occurs in all patients within the first 3 months of diagnosis to reduce joint erosion. Depending on disease severity and whether poor prognostic features are present, combination therapy may be initiated at the time of diagnosis or after an adequate trial of a DMARD initiated as monotherapy. Starting combination therapy initially is referred to as the step-down approach, wherein one or more agents are discontinued once the disease is controlled. Adding a second or third agent after an adequate trial of DMARD monotherapy is considered a step-up approach. Most clinicians favor the "step-down " approach to slow or reverse the early articular damage as soon as possible.7 The following medication classes are prescribed commonly for the treatment of RA: (a) nonsteroidal anti-inflammatory drugs (NSAIDs); (b) glucocorticoids; (c) nonbiologic DMARDs; and (d) biologic DMARDs. Table 57-3 highlights dosing, safety, monitoring, and patient counseling information for the common nonbiologic and biologic DMARDs.

Figures 57-2 and 57-3 outline the course of treatment according to the American College of Rheumatology (ACR) 2008 Recommendations.18 The recommendations are based on the activity level of the patient's disease, the presence or absence of poor prognostic features, and the duration of disease activity. Figures 57-2 and 57-3 apply to patients who have had RA for less than 6 months. Please consult the ACR guidelines18 for treatment recommendations for patients having RA for 6 months or longer.

Table 57-3 FDA-Approved Nonbiologic and Biologic DMARDs for Treatment of RA

FIGURE 57-2. Recommendations for the use of nonbiologic disease-modifying antirheumatic drugs (DMARDs) in RA patients who have never received DMARDs and who have had RA for less than 6 months. These recommendations do not specifically include the potential role of glucocorticoids or NSAIDs in the management of patients with RA. aSee Ref. 18 for definitions of disease activity. b Includes functional limitation (defined using standard measurement scales such as HAQ score or variations of this scale), extraarticular disease (e.g., presence of rheumatoid nodules, secondary Sjogren's syndrome, RA vasculitis, Felty's syndrome, and RA lung disease), rheumatoid factor positivity, pos-

FIGURE 57-2. Recommendations for the use of nonbiologic disease-modifying antirheumatic drugs (DMARDs) in RA patients who have never received DMARDs and who have had RA for less than 6 months. These recommendations do not specifically include the potential role of glucocorticoids or NSAIDs in the management of patients with RA. aSee Ref. 18 for definitions of disease activity. b Includes functional limitation (defined using standard measurement scales such as HAQ score or variations of this scale), extraarticular disease (e.g., presence of rheumatoid nodules, secondary Sjogren's syndrome, RA vasculitis, Felty's syndrome, and RA lung disease), rheumatoid factor positivity, pos-

itive anti-CCP antibodies, or bony erosions by radiography. cOnly recommended for patients with high disease activity with features of poor prognosis. (HCQ, hydroxychloroquine; LEF, leflunomide; MIN, minocycline; MTX, methotrexate; SSZ, sulfasalazine.) (From Ref. 18.)

Patients who have had RA for less than 6 months and have been determined to have low disease activity and no poor prognostic features may be treated with a singleagent nonbiologic DMARD (hydroxychloroquine, minocycline, leflunomide, methotrexate, or sulfasalazine) (Fig. 57-2). If patients with low disease activity do have poor prognostic features, treatment should be started with leflunomide, methotrexate, or sulfasalazine. Patients with moderate or high disease activity but without poor prognostic features may receive initial treatment with sulfasalazine, leflunomide, metho-trexate, or the combination of methotrexate and hydroxychloroquine. Patients with moderate or high disease activity and evidence of poor prognostic features may receive initial single-drug therapy with leflunomide or methotrexate; however, combination therapy may also be started initially in these patients using methotrexate/ hydroxychloroquine, methotrexate/sulfasalazine, or methotrexate/sulfasalazine/hy-droxychloroquine.

Biologic DMARDs are usually considered after failure of nonbiologic DMARDs. Patients with early RA (less than 6 months) and low or moderate disease activity are generally not candidates for biologic DMARDs. In contrast, patients who have had RA for less than 6 months but have had high disease activity for less than 3 months and features of poor prognosis should be considered for treatment with a TNF antagonist (etanercept, infliximab, adalimumab, golimumab, or certolizumab pegol) plus methotrexate (Fig. 57-3). Because of treatment expense, this option should be considered only in patients who have no limitations due to cost or insurance coverage. Other biologic DMARDs may be considered under certain circumstances.

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