What is the recommended treatment for rheumatoid arthritis?

Recommended Treatment for Rheumatoid Arthritis

Methotrexate (MTX) at 15-25 mg weekly is the recommended first-line treatment for rheumatoid arthritis, with the addition of low-dose glucocorticoids (≤10 mg/day prednisone) for the first 3-6 months as bridging therapy, followed by a treat-to-target approach with escalation to combination therapy or biologics if treatment targets are not met. 1

Initial Treatment Strategy

First-Line Therapy

• Start with methotrexate at 15-25 mg weekly 1
  • Initial dose should not be less than 10 mg/week 2
  • Oral route is preferred initially 2
  • Consider switching to subcutaneous route if there is poor compliance, inadequate effectiveness, or gastrointestinal side effects 2
• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for the first 3-6 months as bridging therapy 1
• Always prescribe folic acid supplementation (minimum 5 mg once weekly, taken at a distance from MTX dose) to reduce adverse effects 2, 3

Alternative First-Line Options

• If MTX is contraindicated, consider leflunomide or sulfasalazine as alternative first-line DMARDs 1

Monitoring and Disease Assessment

Required Baseline Tests

• Full blood count with differential and platelet counts
• Serum transaminases and creatinine (with creatinine clearance calculation)
• Chest radiograph
• Hepatitis B and C serology
• Serum albumin 2

Monitoring Schedule

• Assess disease activity every 1-3 months in active disease 1
• Laboratory monitoring (CBC, liver function, renal function):
  • Monthly for first 3 months
  • Every 4-12 weeks thereafter 2
• Aim for remission or low disease activity in all patients 1
• If no improvement by 3 months or target not reached by 6 months, adjust therapy 1

Treatment Escalation Algorithm

For Patients with Inadequate Response to MTX

1. First escalation step (if inadequate response at 3-6 months):

   • Increase MTX dose up to 20-25 mg/week at 6-week intervals 1, 2

2. Second escalation step (based on disease activity):

   • For low/moderate disease activity without poor prognostic factors:

     • Add hydroxychloroquine and sulfasalazine (triple therapy) OR
     • Switch to subcutaneous MTX if oral MTX is ineffective 1

   • For high disease activity or poor prognostic factors:

     • Add a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) 1
     • Options include TNF inhibitors (e.g., adalimumab), abatacept, or IL-6 receptor antagonists 1

Biologic Therapy Considerations

• Adalimumab (Humira) is indicated for reducing signs and symptoms, inhibiting structural damage progression, and improving physical function in moderate to severe RA 4
• Standard dosage: 40 mg subcutaneously every other week 4
• Can be used alone or in combination with MTX or other non-biologic DMARDs 4
• For patients not taking MTX, consider increasing adalimumab to 40 mg weekly or 80 mg every other week if needed 4

Management of Treatment Failures

If First Biologic Fails

• Switch to a different biologic agent with the same or different mechanism of action 1
• For TNF inhibitor failures:
  • Consider another TNF inhibitor, abatacept, tocilizumab, rituximab, or a JAK inhibitor 1
  • Rituximab may be more effective in seropositive patients (RF+, anti-CCP+)
  • Abatacept or tocilizumab may be preferred in seronegative patients who have failed TNF inhibitors 1

Important Safety Considerations

MTX Safety

• Use caution with MTX in patients with diminished hepatic/renal function or decreased folate stores 5
• Avoid concomitant use with NSAIDs without careful monitoring, as NSAIDs can reduce tubular secretion of MTX and enhance toxicity 5
• Monitor for common adverse effects: nausea (more common with higher starting doses) 6, transaminitis, cytopenia

Biologic Safety

• Screen for tuberculosis and hepatitis B/C before starting biologics 1
• Use caution with JAK inhibitors in patients with cardiovascular risk factors 1
• Monitor for serious infections during treatment with TNF inhibitors like adalimumab 4
• Discontinue biologic therapy if serious infection or sepsis develops 4

Treatment Tapering

• Only consider tapering after achieving sustained remission
• First taper glucocorticoids, then consider cautious tapering of biologics
• Only consider tapering conventional DMARDs after long-term sustained remission 1

Common Pitfalls to Avoid

• Inadequate monitoring leading to delayed treatment adjustments 1
• Premature switching before allowing adequate trial duration (3-6 months) 1
• Neglecting the treat-to-target approach, which leads to worse outcomes 1
• Insufficient folate supplementation, which increases MTX toxicity 3
• Failure to escalate MTX to effective doses before adding or switching to biologics 7