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

First-Line Treatment: Methotrexate (MTX)

For this 90-year-old patient with polyarthritis, fever, small joint stiffness, and significantly elevated rheumatoid factor (RF 100), methotrexate is the first-line disease-modifying antirheumatic drug (DMARD) that must be initiated immediately, combined with short-term low-dose corticosteroids for rapid symptom control while MTX takes effect. 1, 2

Rationale for MTX as First-Line Therapy

• MTX is the anchor drug and must be started immediately upon diagnosis to prevent irreversible joint damage, regardless of age 1, 2, 3, 4, 5
• The FDA explicitly indicates MTX for management of severe, active rheumatoid arthritis in adults 2
• This patient has poor prognostic factors (high RF of 100, polyarticular involvement, systemic symptoms with fever) that demand aggressive treatment from the outset 1
• Delaying DMARD initiation leads to irreversible joint damage - this is a critical pitfall to avoid 1

Optimal Treatment Regimen

Start MTX 15-25 mg weekly immediately, with the goal of rapidly escalating to 25 mg weekly within a few weeks 6, 1, 2

• Add folic acid supplementation to reduce toxicity 4, 5
• Simultaneously add low-dose prednisone (≤10 mg/day) for rapid symptom relief while MTX takes effect (typically 3-6 weeks) 1, 7
• Use corticosteroids at the lowest dose for the shortest duration (less than 3 months) 1, 7
• After 1-2 years, long-term corticosteroid risks (cataracts, osteoporosis, fractures, cardiovascular disease) outweigh benefits 6, 1

Why NSAIDs Alone Are Inadequate

• NSAIDs provide only symptomatic relief without disease modification - they do not prevent radiographic progression or joint damage 1, 8, 9
• NSAIDs control pain and inflammation but are not disease-modifying therapy 8, 9
• The FDA label for MTX explicitly states it is indicated after "insufficient therapeutic response to, or intolerance of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents" 2

Why Corticosteroids Alone Are Inadequate

• High-dose corticosteroids alone are not disease-modifying therapy and do not prevent radiographic progression 1
• Corticosteroids should only be used as adjunctive therapy to bridge until DMARDs take effect 1, 7
• Using corticosteroids without DMARDs leads to continued joint destruction despite symptom control 1

Treatment Monitoring and Goals

• Aim for remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10) as the treatment target 6, 1
• Monitor disease activity every 1-3 months during active disease 1, 4
• Expect >50% improvement within 3 months; if not achieved, escalate therapy 1
• Target must be attained within 6 months 1
• Therapeutic response to MTX usually begins within 3-6 weeks, with continued improvement for another 12 weeks or more 2

Escalation Strategy if MTX Inadequate

If the patient does not achieve target by 6 months on optimized MTX:

• Add hydroxychloroquine and sulfasalazine for triple-DMARD therapy 6, 1
• Alternatively, add a biologic DMARD (TNF inhibitor, abatacept, tocilizumab) to MTX 6, 1
• Allow 3-6 months to fully assess efficacy of any new treatment modification 6, 1

Critical Pitfalls to Avoid

• Never delay DMARD initiation - starting with NSAIDs or corticosteroids alone while "waiting to see" leads to irreversible joint damage 1
• Never undertreat with suboptimal MTX doses (<15 mg weekly initially, failure to escalate to 25 mg weekly) 1
• Never continue inadequate therapy beyond 3-6 months without escalation if targets are not met 1
• In this elderly patient with high RF and polyarticular disease, aggressive combination therapy from the start is warranted, not a conservative approach 1

Special Considerations for This Patient

• The significantly elevated RF (100, normal <58) predicts more aggressive disease and makes this patient a candidate for early combination therapy 6, 1
• The presence of fever suggests high disease activity requiring immediate aggressive treatment 1
• Before starting MTX, obtain baseline complete blood count, hepatic function tests, and renal function 2, 4
• The advanced age (90 years) requires careful monitoring but is not a contraindication to MTX therapy 2