What is the most appropriate management for a 30-year-old man presenting with symptoms of Rheumatoid Arthritis (RA) for the first time, including active arthritis, morning stiffness, and a positive Rheumatoid Factor (RF)?

Management of Early Rheumatoid Arthritis

Methotrexate plus hydroxychloroquine and short-term steroids (option C) is the most appropriate management for this 30-year-old man with newly diagnosed RA presenting with active arthritis, morning stiffness, and positive RF. 1

Rationale for Treatment Selection

First-Line Therapy Considerations

• Methotrexate is considered the anchor drug for RA treatment and should be part of the first treatment strategy in patients at risk of persistent disease 1, 2
• Early intervention is critical - treatment should ideally begin within 3 months of symptom onset to take advantage of the "window of opportunity" 1
• This patient has several poor prognostic factors:
  • Active arthritis
  • Morning stiffness
  • Positive rheumatoid factor

Why Combination Therapy is Superior to Monotherapy

1. Methotrexate alone (option A) is insufficient for this patient with active disease and positive RF, which indicates higher risk for persistent and erosive disease 1, 2

2. Methotrexate plus hydroxychloroquine (option B) is better than monotherapy but lacks the rapid anti-inflammatory effect needed for active disease 1

3. Methotrexate, hydroxychloroquine, and steroids (option C) provides:

   • Rapid symptom control from steroids
   • Disease-modifying effects from both DMARDs
   • Better radiographic outcomes 1

4. Methotrexate with cyclophosphamide or sulfasalazine (option D) is not recommended as first-line therapy:

   • Cyclophosphamide has excessive toxicity for early RA
   • While sulfasalazine is a valid DMARD, the combination with hydroxychloroquine and steroids has shown better outcomes 1

Treatment Protocol Details

Methotrexate Administration

• Starting dose: 7.5-15 mg once weekly 3
• Can be escalated to 20-25 mg weekly as needed 2, 3
• Subcutaneous administration may provide more rapid response and better absorption 4
• Monitor CBC, liver function, and renal function before and during therapy 3

Hydroxychloroquine

• Typically dosed at 200-400 mg daily
• Provides added benefit when combined with methotrexate 5
• Lower toxicity profile compared to other DMARDs

Glucocorticoids

• Should be used at lowest effective dose for shortest time possible (ideally <6 months) 1
• Options include:
  • Oral prednisone (5-10 mg daily) as bridging therapy 1
  • Intra-articular injections for specific affected joints 1
  • Initial higher dose with rapid taper to minimize long-term side effects

Monitoring and Follow-up

• Assess disease activity every 1-3 months until remission is achieved 2
• Use validated measures such as DAS28, CDAI, or SDAI 2
• Target remission or low disease activity within 6 months 6
• If treatment target not achieved within 3-6 months, consider treatment modification 1
• Monitor for methotrexate side effects: hepatotoxicity, bone marrow suppression, pulmonary toxicity 3

Common Pitfalls to Avoid

1. Delaying DMARD initiation - Treatment should start within 3 months of symptom onset 1, 2
2. Inadequate methotrexate dosing - Underdosing is common; optimal dosing is 15-25 mg weekly 3, 7
3. Prolonged steroid use - Should be temporary (<6 months) to minimize side effects 1
4. Insufficient monitoring - Regular assessment of disease activity and drug toxicity is essential 2
5. Failure to adjust therapy - If response is inadequate after 3-6 months, treatment should be modified 1, 6

The evidence strongly supports that early, aggressive combination therapy with methotrexate, hydroxychloroquine, and short-term steroids provides the best balance of rapid symptom control, disease modification, and safety for this patient with newly diagnosed, active RA and positive RF.