What is the first line treatment for rheumatoid arthritis?

First-Line Treatment for Rheumatoid Arthritis

Methotrexate should be started immediately as the first-line treatment for rheumatoid arthritis, at a dose of 15-25 mg weekly (oral or subcutaneous) with folic acid supplementation, combined with short-term low-dose glucocorticoids for up to 6 months. 1

Initial Treatment Strategy

Methotrexate as Anchor Drug

• Start methotrexate as soon as RA is diagnosed at 15 mg weekly, rapidly escalating to 25-30 mg weekly within a few weeks to reach optimal dosing 1, 2
• Administer with folic acid 1 mg daily to reduce side effects 2, 3
• Subcutaneous administration should be considered if oral methotrexate at doses >15 mg/week causes gastrointestinal side effects or shows inadequate response, as bioavailability is superior 4
• Maximum efficacy may not be evident until 4-6 months of treatment, so maintain optimal dosing (25-30 mg weekly) for at least 3 months before declaring treatment failure 1

Glucocorticoid Bridge Therapy

• Add low-dose glucocorticoids (prednisone 5-10 mg daily or equivalent) to methotrexate at treatment initiation 1
• Taper glucocorticoids as rapidly as clinically feasible, ideally within 6 months 1
• Glucocorticoids provide superior outcomes when added to methotrexate monotherapy or combination synthetic DMARDs, regardless of the specific DMARD regimen 1

Alternative First-Line Options

When Methotrexate is Contraindicated

If methotrexate cannot be used due to hepatic disease, renal disease, or early intolerance:

• Leflunomide 20 mg daily is the preferred alternative 1
• Sulfasalazine 3-4 g daily (enteric-coated) is equally effective and safe in pregnancy 1
• Both have similar efficacy to methotrexate and can be combined with biologics if needed 1

Combination Synthetic DMARD Strategy

• Combination therapy with multiple conventional synthetic DMARDs (e.g., methotrexate + sulfasalazine + hydroxychloroquine) can be used as first-line treatment instead of methotrexate monotherapy, particularly in DMARD-naïve patients 1
• This approach is equally valid as monotherapy when combined with glucocorticoids 1

Treatment Targets and Monitoring

Goal-Oriented Approach

• Aim for clinical remission or low disease activity as the treatment target 1
• Monitor disease activity every 1-3 months using composite measures (tender/swollen joint counts, pain scales, functional assessments) 1, 2
• If no improvement by 3 months or target not reached by 6 months, adjust therapy 1

When to Escalate Treatment

After 3-6 months of optimal methotrexate therapy (with glucocorticoids):

• If poor prognostic factors are present (RF/ACPA positive, high disease activity, early erosions): add a biologic DMARD (TNF inhibitor, abatacept, tocilizumab, or rituximab) combined with methotrexate 1
• If poor prognostic factors are absent: switch to another conventional synthetic DMARD strategy before considering biologics 1

Critical Implementation Details

Dosing Optimization

• Reach 25-30 mg weekly methotrexate within a few weeks of starting treatment 1
• Maintain maximum tolerated dose for at least 8 weeks, recognizing full efficacy requires 4-6 months 1
• Consider subcutaneous route if oral dosing >15 mg/week is poorly tolerated or ineffective 4

Baseline Monitoring

• Obtain CBC, liver enzymes, creatinine, and hepatitis B/C screening before starting methotrexate 2, 3
• Screen for latent tuberculosis before any biologic therapy 5

Common Pitfalls to Avoid

• Do not underdose methotrexate - many patients receive suboptimal doses (<15 mg/week) and are prematurely labeled as treatment failures 1, 4
• Do not wait too long to escalate - if no improvement by 3 months, begin adjusting therapy rather than waiting the full 6 months 1
• Do not continue glucocorticoids long-term - taper as rapidly as possible to minimize toxicity while maintaining disease control 1

Special Considerations

Exceptional Rapid Escalation

In rare patients with exceptionally high risk of rapid progression (very high disease activity, high-titer autoantibodies, early erosive disease), starting a biologic agent plus methotrexate as first-line therapy may be considered, though this is not standard practice and has lower cost-effectiveness on a population level 1