What is the initial treatment for rheumatoid arthritis?

Initial Treatment for Rheumatoid Arthritis

Start methotrexate 15 mg weekly with folic acid 1 mg daily, escalating to 20-25 mg weekly within 4-6 weeks, combined with low-dose prednisone 5-10 mg daily tapered to 5 mg by week 8. 1, 2, 3

Starting Methotrexate Monotherapy

The evidence strongly favors methotrexate monotherapy as initial treatment over combination conventional DMARDs or biologics for most patients:

• Begin oral methotrexate at 15 mg weekly, not lower doses, as this provides optimal initial efficacy while allowing room for dose escalation 1, 2, 3
• Always prescribe folic acid 1 mg daily to reduce gastrointestinal and hepatic side effects without compromising methotrexate efficacy 1, 2, 4, 5
• Escalate rapidly to 20-25 mg weekly within 4-6 weeks if disease activity persists, using 5 mg increments 2, 3, 6
• Lower doses are required in elderly patients and those with chronic kidney disease 1, 3

The Mayo Clinic guidelines emphasize that "the balance of efficacy/toxicity favours methotrexate monotherapy over combination with other conventional DMARDs," supported by the 2010 Cochrane review showing no statistically significant advantage for initial combination therapy 1. The TEAR trial demonstrated that initial methotrexate monotherapy with step-up at 6 months produces equivalent 2-year outcomes to initial combination therapy with biologics 1.

Adding Low-Dose Prednisone

Combine methotrexate with short-term low-dose prednisone (5-10 mg daily) from the start, tapering to 5 mg daily by week 8 and continuing to taper over 2-4 months total 1, 7, 2:

• This combination provides superior disease control and slows radiographic progression compared to methotrexate alone 1, 2
• The disease-modifying and erosion-inhibiting benefits are sustained for at least 2 years with minimal corticosteroid-related adverse effects 1
• Achieves remission in 40-50% of patients 2

Critical 3-Month Assessment Point

Reassess disease activity at 3 months - this is the most useful time to predict probability of achieving remission at 1 year 1, 3:

• If low disease activity is achieved, continue current therapy 3
• If moderate disease activity persists despite optimized methotrexate (20-25 mg weekly), add sulfasalazine and hydroxychloroquine for triple DMARD therapy, or switch to subcutaneous methotrexate 3, 6
• If high disease activity persists, add a biologic agent such as a TNF inhibitor or abatacept 3

Over 75% of patients achieving low disease activity or remission at 3 months remain in remission at 1 year 1.

Monitoring Requirements

• Assess disease activity every 1-3 months until treatment target is reached using composite measures like SDAI or CDAI 1, 3
• Monitor tender and swollen joint counts, patient and physician global assessments, ESR, and CRP 1
• Check liver function tests and complete blood count regularly 2

Important Caveats

Do not start with combination biologic therapy unless contraindications to methotrexate exist - practical and cost considerations strongly favor initial methotrexate therapy, and the likely response to methotrexate cannot be reliably predicted based on current clinical assessments 1. The European League Against Rheumatism concludes that initial intensive treatment provides better outcomes mainly in patients with severe disease, making initial DMARD monotherapy with methotrexate the reasonable course of action for most patients 1.

Switch to subcutaneous methotrexate before adding other DMARDs if inadequate response occurs on oral methotrexate, as this may overcome absorption issues 2, 3, 6.

Non-Pharmacologic Interventions

Incorporate from the start 1, 3:

• Dynamic exercise programs with aerobic and progressive resistance training 1
• Occupational therapy for joint protection techniques and assistive devices 1
• Patient education about disease management and self-management skills 1, 3
• Cognitive behavioral therapy for patients with fatigue 1, 3