What is the diagnosis and treatment for Rheumatoid Arthritis (RA)?

From the Guidelines

Rheumatoid arthritis treatment should start with disease-modifying antirheumatic drugs (DMARDs) like methotrexate, as soon as the diagnosis is made, with the goal of reaching remission or low disease activity in every patient. This approach is supported by the most recent guidelines, including the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.

Key Principles of Treatment

• Therapy with DMARDs should be initiated immediately after diagnosis, as the disease will not remit spontaneously 1
• Treatment should aim at reaching a target of sustained remission or low disease activity in every patient, with frequent monitoring (every 1-3 months) and adjustments as needed 1
• Methotrexate is a preferred initial DMARD, with a starting dose of 7.5-10mg weekly, potentially increasing to 20-25mg weekly, often with folic acid supplementation to reduce side effects 1
• In cases of methotrexate contraindication or intolerance, leflunomide or sulfasalazine should be considered as part of the first treatment strategy 1

Additional Treatment Considerations

• For symptom management, NSAIDs such as naproxen (500mg twice daily) or ibuprofen (400-800mg three times daily) can provide relief 1
• In more severe cases, biological DMARDs like adalimumab (40mg subcutaneously every two weeks) or etanercept (50mg weekly) may be added, with the goal of minimizing disease activity and reaching a predefined target (low disease activity or remission) 1
• Corticosteroids like prednisone (5-10mg daily) can help manage flares but should be used short-term due to side effects, and tapered as rapidly as clinically feasible 1
• Regular physical therapy, gentle exercise, and joint protection techniques are essential components of treatment, to prevent joint destruction and disability, and improve quality of life 1

Treatment Adjustments and Monitoring

• Treatment decisions should be reevaluated within a minimum of 3 months based on efficacy and tolerability of the DMARD(s) chosen, with adjustments made as needed to reach the treatment target 1
• Disease activity levels should be calculated using RA disease activity measures endorsed by the ACR, to guide treatment decisions and monitor response to therapy 1
• Patients should be at target (low disease activity or remission) for at least 6 months prior to tapering, with dose reduction or gradual discontinuation of DMARDs considered in patients with sustained remission 1

From the FDA Drug Label

B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production. In RA patients, treatment with RITUXAN induced depletion of peripheral B lymphocytes, with the majority of patients demonstrating near complete depletion (CD19 counts below the lower limit of quantification, 20 cells/µl) within 2 weeks after receiving the first dose of RITUXAN.

Rheumatoid Arthritis Treatment: Rituximab is used to treat rheumatoid arthritis (RA) by depleting B cells, which play a role in the pathogenesis of RA.

• The majority of patients show peripheral B-cell depletion for at least 6 months after treatment with rituximab.
• Treatment with rituximab is associated with reduction of certain biologic markers of inflammation, such as interleukin-6 (IL-6), C-reactive protein (CRP), and rheumatoid factor (RF) 2.
• Leflunomide is also indicated for the treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms, inhibit structural damage, and improve physical function 3.

From the Research

Treatment Options for Rheumatoid Arthritis

• Methotrexate is considered the preferred disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis 4, 5
• Combination therapy with methotrexate and other DMARDs, such as sulfasalazine and hydroxychloroquine, can be effective in controlling disease activity and preventing joint damage 4, 6
• Biologic DMARDs, such as TNF-alpha antagonists, can be used in combination with methotrexate to improve treatment outcomes 5
• Targeted synthetic DMARDs, such as tofacitinib, can also be used to treat rheumatoid arthritis 4

Efficacy of Different Treatment Regimens

• Methotrexate + sulfasalazine + hydroxychloroquine (triple therapy) is a effective treatment regimen for rheumatoid arthritis 4, 6
• Leflunomide-based triple therapy is non-inferior to sulfasalazine-based triple therapy in methotrexate-failed rheumatoid arthritis patients 7
• Methotrexate + biologic DMARDs can be effective in preventing joint damage and improving treatment outcomes 4, 5

Safety and Tolerability of Treatment Regimens

• Methotrexate is generally well-tolerated, but can cause gastrointestinal and hematological disorders 5
• Combination therapy with methotrexate and other DMARDs can be associated with an increased risk of adverse events 4
• Biologic DMARDs can be associated with an increased risk of severe adverse events, such as infections and malignancies 5