What are the treatment options for Rheumatoid Arthritis (RA)?

From the Guidelines

Treatment for rheumatoid arthritis should prioritize a shared decision-making process, with early evaluation, diagnosis, and management, and consideration of disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, hydroxychloroquine, and sulfasalazine, as recommended by the 2021 American College of Rheumatology guideline 1. The primary goal of treatment is to minimize disease activity and achieve low disease activity or remission, using a treat-to-target approach. Conventional DMARDs (csDMARDs) such as methotrexate, hydroxychloroquine, and sulfasalazine are the initial treatment of choice, with biologic DMARDs (bDMARDs) like TNF inhibitors (etanercept, adalimumab, infliximab) considered for patients with inadequate response to csDMARDs 1. Key considerations in treatment decisions include:

• Disease activity levels, calculated using RA disease activity measures endorsed by the ACR
• Patient preferences and values
• Potential contraindications to specific treatments
• Regular monitoring and adjustment of treatment to achieve target disease activity levels Some key medications and their uses include:
• Methotrexate, starting at 7.5-10mg weekly, potentially increasing to 20-25mg
• Hydroxychloroquine and sulfasalazine, which may be used in combination with methotrexate
• Biologic DMARDs like TNF inhibitors (adalimumab, etanercept) for patients with inadequate response to csDMARDs
• Targeted synthetic DMARDs (tsDMARDs) like JAK inhibitors (tofacitinib, baricitinib, upadacitinib) for patients with inadequate response to bDMARDs 1. Regular physical therapy, lifestyle changes, and sometimes surgery may also be necessary to manage the condition and improve quality of life.

From the FDA Drug Label

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 Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis.

Treatment for Rheumatoid Arthritis

• Leflunomide is indicated for the treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms, inhibit structural damage, and improve physical function 2.
• Rituximab is used to treat rheumatoid arthritis by depleting B cells, which are believed to play a role in the pathogenesis of RA 3. Key Points
• Leflunomide can be used alone or in combination with other medications, but its use with certain medications has not been adequately studied 2.
• Rituximab treatment in RA patients was associated with reduction of certain biologic markers of inflammation, such as interleukin-6 (IL-6) and C-reactive protein (CRP) 3.

From the Research

Treatment Options for Rheumatoid Arthritis

• Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA), with a good efficacy/toxicity ratio 4
• The treatment of RA is a dynamic process, requiring a balance between benefits and risks, and MTX continues to serve as a reference point even with the introduction of newer biological agents 4
• Effective treatments for RA include oral conventional synthetic DMARDs (e.g., methotrexate), injectable biologic DMARDs, and targeted synthetic DMARDs (oral) 5

Treatment Guidelines and Strategies

• Key recommendations for treating RA include starting effective treatment immediately with DMARDs to reduce disability, using effective doses of methotrexate with folic acid as the initial treatment, and rapidly escalating treatment with various DMARDs if methotrexate alone is not effective 5
• A treat-to-target strategy aimed at reducing disease activity by at least 50% within 3 months and achieving remission or low disease activity within 6 months can prevent RA-related disability 6
• Early diagnosis and treatment of RA can avert or substantially slow progression of joint damage in up to 90% of patients, thereby preventing irreversible disability 6

Comparison of Treatment Options

• Most novel DMARDs, when used in combination with MTX, demonstrate comparable American College of Rheumatology (ACR) responses, with the exception of anakinra plus MTX, which is less efficacious 7
• Tocilizumab monotherapy displays higher ACR responses than anti-tumor necrosis factor agents (aTNF) or tofacitinib, while ACR responses with tocilizumab plus MTX are similar to those with tocilizumab monotherapy 7
• The safety of long-term use of common conventional DMARDs, including methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine, is a concern, and their use should be carefully monitored 8