What is the recommended treatment for Rheumatoid Arthritis (RA)?

Treatment for Rheumatoid Arthritis (RA)

Methotrexate (MTX) is the recommended first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis, started at 15 mg/week with folic acid supplementation, and should be initiated as early as possible after diagnosis. 1

Initial Treatment Approach

First-Line Therapy

• Start MTX at 15 mg/week with folic acid 1 mg/day
• Increase MTX dose to an optimal dose of 25 mg/week as tolerated
• Add short-term low-dose oral glucocorticoids (≤10 mg prednisone equivalent/day) for up to 6 months, tapering as rapidly as clinically feasible 1
• Consider intra-articular glucocorticoid injections for local symptom relief 1

MTX Administration

• Begin with oral administration
• Consider switching to subcutaneous administration if:
  • Poor compliance with oral form
  • Inadequate response to oral MTX
  • Gastrointestinal side effects 2
• Subcutaneous administration has better bioavailability and may be more effective than oral administration 2

Monitoring During Initial Treatment

• Assess disease activity every 1-3 months using composite measures (DAS28, CDAI, SDAI) 1
• Monitor for adverse effects with regular laboratory tests:
  • Complete blood count
  • Liver function tests
  • Renal function tests
  • These should be obtained at least monthly for the first 3 months, then every 4-12 weeks 3

Treatment Adjustment

If Target Not Reached After 3-6 Months

1. Without poor prognostic factors:

   • Change to another conventional synthetic DMARD (csDMARD) such as sulfasalazine or leflunomide 1

2. With poor prognostic factors (high number of swollen/tender joints, elevated ESR/CRP, positive rheumatoid factor and/or anti-CCP antibodies, early erosions):

   • Add a biologic DMARD (bDMARD), typically a TNF inhibitor 1
   • Common TNF inhibitors include etanercept, adalimumab, and golimumab

For Patients Who Fail TNF Inhibitors

• Rituximab in combination with MTX is recommended for patients who have failed previous DMARDs, including TNF inhibitors 1, 4
• Rituximab is administered as an IV infusion and works by targeting CD20-positive B-lymphocytes 4

Disease Activity Assessment

Target Goals

• Primary goal: Achieve remission or low disease activity 1
• Disease activity thresholds:

  State	DAS28	CDAI	SDAI
  Remission	<2.6	≤2.8	≤3.3
  Low activity	2.6-3.2	>2.8-10	>3.3-11
  Moderate activity	3.2-5.1	>10-22	>11-26
  High activity	>5.1	>22	>26

Advanced Treatment Options

Combination Therapy

• Combination of MTX and a TNF-alpha antagonist is more effective than MTX monotherapy on functional status and symptoms, especially in initially severe RA 5
• When using combination therapy, maintain the MTX dosage and route of administration 6

For Refractory Disease

• If TNF inhibitors fail, rituximab with MTX has shown effectiveness 5
• Other options include IL-6 inhibitors (tocilizumab) or T-cell co-stimulation modulators (abatacept) 1

Tapering Considerations

• Consider tapering medication only after sustained low disease activity or remission for at least 6 months 1
• Taper in this order: first glucocorticoids, then biologics, then conventional DMARDs 1
• Reduce doses gradually rather than abrupt discontinuation 1

Common Pitfalls to Avoid

1. Inadequate MTX dosing: Starting with too low a dose (less than 10 mg/week) may lead to suboptimal response 3

2. Premature treatment changes: MTX should be continued for at least 6 months (as long as there is some response within 3 months) to accurately assess efficacy 6

3. Prolonged glucocorticoid use: Increases risk of adverse effects 1

4. Infrequent monitoring: Can lead to inadequate treatment adjustments or delayed recognition of adverse effects 1

5. Overlooking folic acid supplementation: Folate supplementation (minimum 5 mg weekly) can reduce MTX side effects 3

Adjunctive Therapies

• NSAIDs may be used for symptomatic relief but should not delay initiation of DMARDs 1
• Dynamic exercise programs incorporating aerobic exercise and strength training 1
• Occupational therapy and assistive devices to protect joints and improve function 1
• Patient education on disease management and self-care skills 1

By following this treatment algorithm for RA, focusing on early MTX initiation with appropriate dose escalation and timely addition of biologics when needed, patients have the best chance of achieving remission or low disease activity, thereby preventing joint damage and disability.