What is the initial treatment for rheumatoid arthritis?

Initial Treatment for Rheumatoid Arthritis

Start methotrexate at 15 mg weekly with folic acid 1 mg daily, combined with low-dose prednisone (5-10 mg daily) tapered to 5 mg by week 8, then continue tapering over 2-4 months total. 1, 2

Methotrexate Dosing Strategy

• Begin with oral methotrexate 15 mg weekly and escalate to 20-25 mg weekly within 4-6 weeks based on disease response and tolerability 3, 1, 2
• Lower starting doses (10 mg weekly minimum) may be appropriate for elderly patients or those with chronic kidney disease 3, 2
• Maximum therapeutic effect requires 4-6 months of therapy, though clinical improvement may be seen as early as 3-6 weeks 1, 4
• Always prescribe folic acid supplementation (minimum 1 mg daily) to reduce gastrointestinal and other adverse effects 3, 1, 5

Prednisone Co-Administration

• Add short-term low-dose prednisone (5-10 mg daily) at treatment initiation, starting with a moderate dose and tapering to 5 mg daily by week 8 3, 6, 1
• Continue tapering prednisone over 2-4 months total duration 6, 1
• This combination provides superior disease control, slows radiographic progression, and achieves remission in 40-50% of patients compared to methotrexate alone 1
• The disease-modifying and erosion-inhibiting benefits of low-dose prednisone (5-10 mg daily) are sustained for at least 2 years with minimal adverse effects 3

Rationale for Methotrexate Monotherapy Over Initial Combination

The evidence favors methotrexate monotherapy over initial combination with other conventional DMARDs or biologics based on the TEAR trial and practical considerations 3:

• The TEAR trial showed no advantage of initial combination therapy with etanercept over methotrexate monotherapy with step-up at 6 months for inadequate response 3
• A 2010 Cochrane review found no statistically significant advantage for initial combination therapy using methotrexate and other conventional DMARDs over methotrexate monotherapy 3
• While trials with TNF inhibitors or abatacept combined with methotrexate show greater efficacy than methotrexate alone, these studies have limitations including patient selection bias and fixed protocols that don't reflect real-world longitudinal care 3
• Practical and cost considerations strongly favor initial methotrexate therapy 3

Critical Assessment Timeline

Assess disease activity at 3 months after treatment initiation—this is the most critical time point for predicting long-term remission 3:

• Patients achieving low disease activity or remission at 3 months have >75% probability of remission at 1 year 3
• If methotrexate optimized to 20-25 mg weekly (or maximum tolerated dose) plus prednisone does not achieve low to moderate disease activity by 3 months, escalate therapy 3
• Continue monitoring disease activity every 1-3 months until remission is achieved 3, 2

Treatment Escalation for Inadequate Response

If inadequate response at 3 months despite optimized methotrexate dosing:

• First, switch from oral to subcutaneous methotrexate before adding other agents, as this may overcome absorption issues 1, 2
• For moderate disease activity: add sulfasalazine and hydroxychloroquine for triple DMARD therapy 2
• For high disease activity: add a biologic agent such as a TNF inhibitor or abatacept 3, 2

Mandatory Baseline Investigations

Before starting methotrexate 1, 7:

• Complete blood count, serum transaminases, serum creatinine with creatinine clearance calculation
• Chest radiograph
• Hepatitis B and C serological screening
• Tuberculosis screening (especially if considering future biologic therapy)
• Serum albumin (recommended)

Monitoring During Treatment

• Full blood count, serum transaminases, and creatinine every 1-1.5 months initially, then every 1-3 months once stable 1, 2, 7
• Hold methotrexate if serum creatinine increases by 50%, transaminases >2× upper limit of normal, or mucositis develops 1
• Consider pneumocystis prophylaxis if prednisone ≥20 mg daily for ≥4 weeks 6, 1

Non-Pharmacologic Adjuncts

While pharmacologic therapy is primary, incorporate 3, 2:

• Patient education about disease pathophysiology and self-management
• Dynamic exercise programs with aerobic and progressive resistance training
• Occupational therapy for joint protection techniques and assistive devices
• Cognitive behavioral therapy for patients with significant fatigue

Common Pitfalls to Avoid

• Do not start with methotrexate doses <10 mg weekly—this is subtherapeutic 8, 7
• Do not wait longer than 3 months to assess response and escalate therapy if needed—delayed intensification leads to worse long-term outcomes 3
• Never omit folic acid supplementation—this significantly reduces toxicity without compromising efficacy 1, 5, 7
• Do not combine methotrexate with other conventional DMARDs initially unless severe disease—monotherapy with appropriate escalation is preferred 3