What is the recommended treatment for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

Methotrexate (MTX) should be the first-line treatment for most patients with rheumatoid arthritis, with treatment aimed at achieving remission or low disease activity through a treat-to-target approach. 1

Initial Treatment Strategy

First-Line Therapy

• Start MTX as soon as RA is diagnosed at 15-25 mg/week (as tolerated) 2, 1
• Initial dosing recommendations:
  • Starting dose should not be less than 10 mg/week 3
  • Oral route is preferred initially 3
  • Consider switching to subcutaneous route for better bioavailability if oral route shows inadequate response or gastrointestinal side effects 3

Adjunctive Therapy with MTX

• Add low-dose glucocorticoids (≤10 mg/day prednisone) as bridge therapy when starting MTX 1
• Taper glucocorticoids as rapidly as clinically feasible (within 6 months) to minimize long-term adverse effects 2, 1
• Prescribe folate supplementation (5 mg weekly, taken at a distance from MTX dose) to reduce adverse effects 3, 4

Monitoring

• Baseline assessment: complete blood count with differential, hepatic enzymes, renal function tests, chest X-ray 5
• Monitor every 1-3 months in active disease 2, 1
• Laboratory monitoring: complete blood count, liver function, and creatinine at least monthly for first 3 months, then every 4-12 weeks 3

Treatment Adjustments

When to Adjust Therapy

• If no improvement after 3 months of treatment or target not reached by 6 months, adjust therapy 2, 1
• Target should be remission (SDAI ≤3.3, CDAI ≤2.8) or low disease activity (SDAI ≤11, CDAI ≤10) 2

Adjustment Options for Inadequate MTX Response

1. For patients without poor prognostic factors:

   • Optimize MTX dose (up to 20-25 mg/week) 2, 3
   • Consider switching to subcutaneous MTX for better bioavailability 2
   • Add another conventional synthetic DMARD (csDMARD) such as sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (triple therapy) 2

2. For patients with poor prognostic factors (high RF/ACPA, high disease activity, early joint damage, failure of 2 csDMARDs):

   • Add a biologic DMARD (bDMARD) or JAK inhibitor 2, 1

Biologic Therapy

First-Line Biologic Options

• TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab) combined with MTX is the standard first-line biologic approach 1, 6
• Other options include:
  • Abatacept (CTLA4-Ig)
  • Tocilizumab (anti-IL-6R)
  • Rituximab (anti-CD20) 2

Biologic Selection Considerations

• Combine biologics with MTX when possible for enhanced efficacy 1
• Consider seropositivity status:
  • Rituximab preferred for seropositive patients
  • Abatacept or tocilizumab for seronegative patients 2, 1

Biologic Failure

• If first TNF inhibitor fails, options include:
  • Switch to another TNF inhibitor (up to 2 trials)
  • Switch to a biologic with different mechanism of action (abatacept, tocilizumab, rituximab) 2
• Allow at least 3-6 months to fully assess efficacy of a biologic agent 1

Special Considerations

Early vs. Established RA

• Early RA (disease duration <6 months):

  • Consider less aggressive approach for low disease activity without poor prognostic factors 2, 1

• Established RA (disease duration ≥6 months):

  • Consider more aggressive treatment escalation 2, 1

Safety Precautions

• Screen for tuberculosis, hepatitis B, and assess baseline immunoglobulin levels before starting biologics 1
• Avoid combining different biologics due to increased infection risk 1
• Monitor for MTX toxicity:
  • Gastrointestinal symptoms (nausea, vomiting)
  • Hepatotoxicity (transaminitis)
  • Bone marrow suppression (cytopenia)
  • Pulmonary toxicity 5

Tapering Therapy

• If persistent remission is achieved after tapering glucocorticoids, consider tapering bDMARDs 2
• In cases of sustained long-term remission, cautious reduction of csDMARD dose could be considered 2

Common Pitfalls to Avoid

• Inadequate MTX dosing (doses below 15 mg/week may be suboptimal) 2, 7
• Failure to supplement with folate (increases risk of adverse effects) 4
• Prolonged glucocorticoid use (should be tapered within 6 months) 1
• Premature switching of therapy before adequate trial (allow 3-6 months) 1
• Inadequate monitoring of disease activity leading to delayed treatment adjustments 1