What is the first-line treatment for a patient with a 10-year history of polyarthritis, fever, small joint stiffness, and a significantly elevated Rheumatoid Factor (RF) level of 100, which is above the normal range of less than 58?

First-Line Treatment for Rheumatoid Arthritis with Poor Prognostic Features

Methotrexate (MTX) is the definitive first-line treatment for this patient with established, seropositive rheumatoid arthritis, initiated at 15-25 mg weekly with folic acid supplementation, combined with short-term low-dose corticosteroids (≤10 mg/day prednisone equivalent) for rapid symptom control while MTX takes effect. 1, 2

Rationale for MTX as Anchor Drug

• MTX must be part of the first treatment strategy in patients with active RA, as it is the most effective conventional DMARD with proven efficacy in preventing radiographic progression 1, 3
• The patient's significantly elevated rheumatoid factor (RF 100, normal <58) represents a poor prognostic marker that mandates aggressive disease-modifying therapy, not symptomatic treatment alone 2
• NSAIDs (Option A) provide only symptomatic relief without disease modification and do not prevent irreversible joint damage 2
• Corticosteroids alone (Option B) are not disease-modifying therapy and do not prevent radiographic progression, though they serve an important adjunctive role 2

Optimal Treatment Regimen

MTX Dosing Strategy

• Start MTX at 15-25 mg weekly (oral or subcutaneous) with folic acid supplementation 1, 2, 3
• Rapidly escalate to the optimal dose of 25-30 mg weekly within a few weeks 1, 2
• Maintain the maximal tolerated dose for at least 3 months, recognizing that maximal efficacy may not be seen until 6 months 1
• If gastrointestinal side effects occur with oral dosing, switch to subcutaneous administration for better absorption and tolerability 1

Adjunctive Corticosteroid Use

• Add short-term glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom control while MTX takes effect 1, 2
• Use the lowest effective dose for the shortest duration (less than 3 months preferred) 2
• After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 1, 2
• Taper and discontinue prednisone once remission or low disease activity is achieved 1, 2

Treatment Targets and Monitoring

Disease Activity Goals

• Primary target: Clinical remission (SDAI ≤3.3 or CDAI ≤2.8) 2
• Acceptable alternative: Low disease activity (SDAI ≤11 or CDAI ≤10) 1, 2

Assessment Timeline

• Monitor disease activity every 1-3 months during active disease 1, 2
• Expect >50% improvement within 3 months 1, 2
• Target must be attained within 6 months 1, 2
• Therapeutic response typically begins within 3-6 weeks, with continued improvement for another 12 weeks or more 3

When to Escalate Therapy

Inadequate Response Criteria

• If <50% improvement at 3 months, adjust therapy 1, 2
• If target not reached at 6 months despite optimal MTX dosing, escalate treatment 1, 2

Escalation Options for Poor Prognostic Features

Given this patient's high RF level (poor prognostic marker), if MTX monotherapy fails:

• Add sulfasalazine + hydroxychloroquine for triple-DMARD therapy 1, 2
• Add a biologic DMARD (TNF inhibitor, abatacept, tocilizumab, or rituximab) to MTX 1, 2
• Patients with poor prognostic factors (high RF, erosive disease) may require earlier biologic escalation 2

Critical Pitfalls to Avoid

• Never delay DMARD initiation—this leads to irreversible joint damage 2
• Never use NSAIDs or corticosteroids alone as they provide only symptomatic relief without disease modification 2
• Never undertreat with suboptimal MTX doses (<25 mg weekly)—this prevents achieving treatment targets 2
• Never accept persistent moderate-high disease activity without treatment escalation 4
• Do not continue long-term corticosteroids beyond 1-2 years due to cumulative toxicity 1, 2

Why Not the Other Options

Option A (NSAID alone): Provides only symptomatic relief without modifying disease course or preventing joint destruction 2

Option B (Corticosteroid alone): Not disease-modifying therapy; does not prevent radiographic progression despite symptom improvement 2

Option C (MTX) is correct and should be combined with short-term corticosteroids for optimal outcomes 1, 2