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

Starting Methotrexate Monotherapy

Methotrexate monotherapy is the preferred initial treatment for most patients with rheumatoid arthritis based on the superior efficacy-to-toxicity ratio compared to combination conventional DMARDs and practical cost considerations. 3

Dosing Strategy

• Begin at 15 mg weekly orally (not less than 10 mg/week), escalating by 5 mg increments every 4-6 weeks to reach 20-25 mg weekly within the first 3 months if needed. 1, 2
• Lower doses may be required in elderly patients and those with chronic kidney disease. 3, 2
• Always prescribe folic acid 1 mg daily to reduce gastrointestinal and other adverse effects. 3, 1, 4

Why Not Initial Combination Therapy?

The TEAR trial demonstrated no advantage of initial combination therapy with TNF inhibitors over methotrexate monotherapy with step-up at 6 months for inadequate response, regarding both clinical and radiographic outcomes at 2 years. 3 A 2010 Cochrane review found no statistically significant advantage for initial combination therapy using methotrexate with other conventional DMARDs over methotrexate monotherapy. 3

Adding Prednisone

Combine methotrexate with short-term low-dose prednisone (5-10 mg daily) at initiation, tapering to 5 mg daily by week 8, then continuing to taper over 2-4 months total. 5, 1 This combination provides:

• Superior disease control 1
• Slowed radiographic progression 3, 1
• Remission in 40-50% of patients 1
• Disease-modifying and erosion-inhibiting benefits sustained for at least 2 years with minimal adverse effects 3

Critical Assessment Timeline

Assess response at 3 months - this is the most useful time point to predict probability of achieving clinical remission at 1 year. 3

If Low Disease Activity at 3 Months:

• Continue current therapy 2
• More than 75% of patients with low disease activity at 3 months achieve remission at 1 year 3

If Inadequate Response at 3 Months:

First, optimize methotrexate dosing to 20-25 mg weekly or switch to subcutaneous administration before adding other agents. 1, 2

If still inadequate after optimization:

• For moderate disease activity: Add sulfasalazine and hydroxychloroquine (triple DMARD therapy) 2
• For high disease activity: Add a biologic agent (TNF inhibitor or abatacept) 2

Monitoring Requirements

Before Starting Treatment:

• Full blood count, serum transaminases, serum creatinine with creatinine clearance calculation, chest radiograph 6
• Hepatitis B and C screening 1, 6
• Latent tuberculosis screening 1

During Treatment:

• Assess disease activity every 1-3 months until remission achieved using composite measures (SDAI or CDAI) 2
• Full blood count, transaminases, and creatinine at least monthly for first 3 months, then every 4-12 weeks 6
• Hold methotrexate if: serum creatinine increases by 50%, transaminases >2× upper limit of normal, or mucositis present 1

Important Caveats

Consider pneumocystis prophylaxis if prednisone ≥20 mg daily for ≥4 weeks. 5, 1

If oral methotrexate ineffective, switch to subcutaneous administration before adding other DMARDs, as absorption may be dose-dependent and variable. 1, 7

The therapeutic target is remission or low disease activity within 6 months, with treatment modification required if no improvement by 3 months. 1, 2

Non-Pharmacologic Adjuncts

Incorporate dynamic exercise programs, occupational therapy for joint protection, patient education about disease management, and cognitive behavioral therapy for fatigue management as part of multidisciplinary care. 3, 2