What is the initial treatment protocol for rheumatoid arthritis (RA)?

Initial Treatment Protocol for Rheumatoid Arthritis

The initial treatment for rheumatoid arthritis should begin with methotrexate (MTX) at 15 mg/week along with folic acid supplementation (1 mg/day), with dose escalation to 20-25 mg/week as tolerated within the first 3 months if needed. 1, 2

Initial Diagnostic Investigations

• Perform clinical examination to detect synovitis, which may be confirmed by ultrasonography if needed 2
• Assess risk factors for persistent/erosive disease including:
  • Number of swollen and tender joints
  • Elevated ESR or CRP
  • Presence of rheumatoid factor and anti-CCP antibodies
  • Radiographic erosions 2
• Mandatory investigations before starting methotrexate:
  • Full blood cell count
  • Serum transaminase levels
  • Serum creatinine with computation of creatinine clearance
  • Chest radiograph 3
• Recommended additional tests:
  • Serological tests for hepatitis B and C
  • Serum albumin assay 3
• For patients with respiratory disease or symptoms, perform lung function tests with determination of diffusing capacity for carbon monoxide 3

Initial Treatment Algorithm

1. First-line therapy: Start methotrexate at 15 mg/week with folic acid 1 mg/day 1, 2

   • Lower doses may be required in elderly patients and those with chronic kidney disease 1
   • Consider short-term systemic glucocorticoids (prednisone starting at moderate dose and tapered to 5 mg/day by week 8) for temporary symptom relief 1, 2

2. Monitoring: Assess disease activity every 1-3 months until treatment target is reached 2

   • Mandatory monitoring tests: full blood cell counts, serum transaminase and creatinine assays
   • Perform these tests at least once a month for the first 3 months, then every 4-12 weeks 3
   • Use composite measures like SDAI or CDAI to assess disease activity 2

3. Critical assessment at 3 months: This is the key timepoint to evaluate treatment response 1

   • If low disease activity (SDAI ≤11, CDAI ≤10) is achieved, continue current therapy 1
   • If moderate disease activity persists (SDAI >11 to ≤26 or CDAI >10 to ≤22), optimize MTX dose to 20-25 mg/week 1
   • If high disease activity persists (SDAI >26 or CDAI >22), consider adding biologic therapy 1

Treatment Escalation at 3-6 Months

• For patients with moderate disease activity after 3-6 months on optimized MTX:

  • Add sulfasalazine and hydroxychloroquine for triple DMARD therapy 1, 2
  • Consider switching to subcutaneous MTX if oral administration is ineffective 1, 4

• For patients with high disease activity at 3 months despite optimized MTX:

  • Add a biologic agent (TNF inhibitor or abatacept) 1, 2
  • TNF inhibitors and abatacept are approved and recommended biologic response modifiers for step-up treatment 1

Treatment Escalation at 6-12 Months

• If target not achieved (SDAI >11, CDAI >10) at 6-12 months:
  • For patients on MTX monotherapy: Add sulfasalazine and hydroxychloroquine for triple DMARD therapy or add a biologic agent (TNF inhibitor or abatacept) 1
  • For patients already on MTX plus biologic therapy: Switch to an alternative biologic response modifier 1

Common Pitfalls to Avoid

• Delaying DMARD therapy beyond 3 months of symptom onset can lead to irreversible joint damage 2
• Using suboptimal doses of MTX (optimal dose range is 15-25 mg/week) 2, 5
• Failing to monitor disease activity regularly and adjust therapy accordingly 2
• Not considering triple DMARD therapy (MTX + sulfasalazine + hydroxychloroquine) before biologics in moderate disease 2
• Neglecting folic acid supplementation, which should be given at a minimal dosage of 5 mg once weekly (at a distance from the MTX dose) to reduce side effects 3

Non-Pharmacological Interventions

• Incorporate dynamic exercises and occupational therapy 2
• Provide patient education about disease management 2
• Implement programs for coping with pain and maintaining work ability 2
• Consider cognitive behavioral therapy for patients with fatigue 1