Management principles for the initial treatment of Rheumatoid Arthritis

Discuss the management principles for the initial treatment of Rheumatoid Arthritis

Current strategies include early aggressive treatment with one or more conventional synthetic DMARDs (csDMARDs; : Systemic Antirheumatic Drugs;  : Immunosuppressive and Immunoregulatory Agents) and/or biologic DMARDs (bDMARDs;: Biologic Agents), in addition to symptomatic therapy with NSAIDs, low-dose prednisone, physical therapy (: Rehabilitative Techniques), occupational therapy, rest, and patient education. Methotrexate has been the most effective antirheumatic drug used and can induce low disease activity as monotherapy in about 30% of patients.

Therapy should be advanced in patients who fail to reach low disease activity or remission with an adequate dose (15–25 mg/week) of methotrexate after 3–6 months. In this situation, therapy may consist of addition of csDMARDs to methotrexate or addition of a bDMARD or targeted synthetic DMARD (tsDMARD, such as tofacitinib or baracitinib) to methotrexate. In the former approach, sulfasalazine and hydroxychloroquine may be added to methotrexate (commonly referred to as triple therapy). Patients intolerant to methotrexate may have leflunomide or, less commonly, azathioprine substituted. Patients who are compliant with triple therapy achieve low disease activity in 40% to 50% of cases without an increase in medication toxicity. In the latter approach, options for bDMARDs and tsDMARDs include anti-tumor necrosis factor α agents, abatacept, tocilizumab, sarilumab, rituximab, tofacitinib, or baracitinib, usually in combination with methotrexate. Patients on their first bDMARD can achieve low disease activity in 40% to 50% of cases. RA patients who fail to respond to an initial biologic agent should be switched to another biologic agent with a different mode of action. Rituximab can be helpful in both seropositive and seronegative disease, but efficacy is better in seropositive RA patients.

Personalized medicine (or perhaps more accurately, precision medicine) is a major area of research in RA. One of the goals of this field is to determine prior to therapy which drug will work best in individual patients in order to avoid costly and ineffective therapies and speed the time to disease control for individual patients. Approaches may include blood tests for inflammatory or autoimmune biomarkers, genetic testing (including gene expression profiles and genes related to drug metabolism), and potentially synovial biopsy to further characterize the immunologic drivers for individual patients. This “precision medicine” approach will be an area of continued research and holds the promise of improved patient outcomes and lower cost of care (through elimination of a trial-and-error approach).

Special attention should be given to preventative therapy including immunizations (flu, pneumonia, zoster), CV disease (smoking, blood pressure control, lipid management, weight loss as appropriate), and osteoporosis (calcium, vitamin D, and other targeted therapy such as antiresorptives).

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