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, escalating to 20-25 mg weekly within 4-6 weeks, combined with low-dose prednisone (5-10 mg daily) tapered to 5 mg daily by week 8, then continued tapering over 2-4 months total. 1, 2

Starting Methotrexate Therapy

• Begin with oral methotrexate 15 mg weekly rather than lower doses, as this provides superior disease control and slows radiographic progression 3, 1
• Escalate by 5 mg increments monthly to reach 20-25 mg weekly within 4-6 weeks if needed for disease control 1, 2
• Always prescribe folic acid supplementation at 1 mg daily to reduce gastrointestinal and other adverse effects 3, 1
• Lower doses may be required in elderly patients and those with chronic kidney disease 3, 2

The evidence strongly favors methotrexate monotherapy over initial combination therapy with other conventional DMARDs based on efficacy/toxicity balance 3. The TEAR trial demonstrated no advantages of initial combination therapy with TNF inhibitors over methotrexate monotherapy with step-up therapy at 6 months for inadequate response 3.

Corticosteroid Bridge Therapy

• Add low-dose prednisone 5-10 mg daily at treatment initiation for disease-modifying and erosion-inhibiting benefits 3, 4, 1
• Taper to 5 mg daily by week 8, then continue tapering over 2-4 months total 4, 1
• This combination achieves remission in 40-50% of patients and provides sustained benefits for at least 2 years with minimal adverse effects 3, 1

Route of Administration

• Prefer oral administration initially for convenience and patient acceptance 3
• Switch to subcutaneous methotrexate if oral administration shows inadequate effectiveness, causes gastrointestinal toxicity, or compliance issues arise 1, 2
• Consider parenteral route from the start for doses >20 mg/week, obesity, very active disease, or polypharmacy 5

Critical Monitoring Timeline

• Assess disease activity at 3 months using composite measures like SDAI or CDAI—this is the most useful time point to predict probability of achieving remission at 1 year 3, 2
• Patients achieving low disease activity or remission at 3 months have >75% probability of remission at 1 year 3
• If inadequate response at 3 months despite optimized methotrexate (20-25 mg weekly), escalate therapy rather than waiting longer 3, 2

Treatment Escalation Strategy

For patients not achieving low disease activity at 3 months:

• First step: Switch to subcutaneous methotrexate if currently on oral administration 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 TNF inhibitor or abatacept 2

The evidence shows that while combination therapy with biologics has greater efficacy in clinical trials, practical considerations including cost and the ability to modify treatment more rapidly in real-world practice favor initial methotrexate monotherapy 3.

Mandatory Baseline Investigations

• Complete blood count, serum transaminases, serum creatinine with creatinine clearance calculation 2
• Chest radiograph 2
• Hepatitis B and C serological testing 1, 2
• Screen for latent tuberculosis before initiating therapy 1

Ongoing Monitoring Requirements

• Assess disease activity every 1-3 months until treatment target is reached 2
• Full blood count, serum transaminases, and creatinine at least monthly for first 3 months, then every 1-3 months 2
• Hold methotrexate if: serum creatinine increases by 50%, transaminases >2× upper limit of normal, or mucositis develops 1

Non-Pharmacological Interventions

• Incorporate dynamic exercises and progressive resistance training, which improve fitness, strength, and lean body mass safely 3
• Provide occupational therapy for joint protection instruction, assistive devices, orthotics, and splints 3, 2
• Consider cognitive behavioral therapy for patients with fatigue to enhance self-management 3, 2
• Multidisciplinary care team including rheumatologist, nurses, physical/occupational therapists, and primary care physician optimizes outcomes 3

Common Pitfalls to Avoid

• Do not start with doses <10-15 mg weekly—this delays achieving therapeutic effect and prolongs disease activity 3, 1, 2
• Do not wait beyond 3 months to escalate therapy if disease activity remains moderate to high—the window for optimal disease modification narrows significantly 3
• Do not omit folic acid supplementation—this is associated with unnecessary toxicity and treatment discontinuation 3, 1
• Do not continue oral methotrexate indefinitely if ineffective—switch to subcutaneous route before adding more expensive agents 1, 2