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

From the Guidelines

Rheumatoid arthritis treatment should be initiated as soon as the diagnosis is made, with the goal of achieving sustained remission or low disease activity, and therapy should be adjusted every 1-3 months if there is no improvement or if the target has not been reached by 6 months, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment of rheumatoid arthritis typically involves a combination of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (400-800mg three times daily) or naproxen (500mg twice daily) for pain and inflammation.

• Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of treatment, with methotrexate (starting at 7.5-10mg once weekly, potentially increasing to 20-25mg weekly) being the first-line option, as supported by the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
• For more severe cases, biologic DMARDs such as TNF inhibitors (etanercept, adalimumab, infliximab) may be added.
• Corticosteroids like prednisone (5-10mg daily) can provide rapid relief during flares but should be used at the lowest effective dose for the shortest time possible due to side effects.

Non-Medication Approaches

Regular physical therapy, gentle exercise, and joint protection techniques are essential non-medication approaches.

• Patients should monitor for medication side effects, including regular blood tests for those on methotrexate, and maintain consistent follow-up with rheumatologists.
• Early aggressive treatment is crucial as it can prevent irreversible joint damage by targeting the underlying immune dysfunction that causes the body to attack its own joint tissues, as emphasized by the European League against Rheumatism recommendations 1.

Monitoring and Adjustment

Monitoring should be frequent in active disease (every 1–3 months), and if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted, as recommended by the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis 1.

• The choice of treatment strategy should be based on a shared decision-making process between the patient and the rheumatologist, taking into account the patient's preferences, comorbidities, and potential risks, as highlighted in the 2021 American College of Rheumatology guideline 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. Leflunomide is indicated in adults for the treatment of active rheumatoid arthritis (RA): to reduce signs and symptoms to inhibit structural damage as evidenced by X-ray erosions and joint space narrowing to improve physical function

Rheumatoid Arthritis Treatment:

• Rituximab (IV) and leflunomide (PO) are both used to treat rheumatoid arthritis.
• Rituximab works by depleting B cells, which play a role in the pathogenesis of RA.
• Leflunomide is used to reduce signs and symptoms, inhibit structural damage, and improve physical function in adults with active RA 2, 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, as it has been shown to relieve pain, reduce the number of affected joints, and provide functional improvement 4.
• Combination therapy with methotrexate and other DMARDs, such as sulfasalazine and hydroxychloroquine ("triple therapy"), has been found to be effective in controlling disease activity and is generally well tolerated 5, 6, 7.
• Biologic DMARDs, such as adalimumab, etanercept, and rituximab, have also been shown to be effective in combination with methotrexate, particularly in patients who have not responded to methotrexate alone 4, 5, 7.

Efficacy of Different Treatment Regimens

• Methotrexate monotherapy has been found to be effective in reducing disease activity, but combination therapy with other DMARDs or biologics may be more effective in achieving remission or low disease activity 5, 8.
• The estimated probability of ACR50 response (a measure of major clinical improvement) was similar between different combination regimens, including triple therapy and biologic DMARDs, ranging from 56-67% 5, 7.
• Radiographic progression was found to be inhibited by combination therapy with methotrexate and biologic DMARDs, but the estimated mean change over one year was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale 5, 7.

Safety and Tolerability of Treatment Regimens

• Methotrexate has been found to have a favorable safety profile, with few treatment withdrawals due to adverse events 4.
• Combination therapy with methotrexate and other DMARDs or biologics has been found to be generally well tolerated, with no significant increase in adverse events compared to monotherapy 5, 6, 7.
• However, some combination regimens, such as methotrexate plus azathioprine, have been found to have a higher rate of withdrawals due to adverse events 5.