What is the recommended initial treatment for lupus?

Initial Treatment for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine (200-400 mg/day) should be prescribed as the cornerstone of initial treatment for all patients with SLE, regardless of disease severity or organ involvement, as it reduces disease flares, limits organ damage, and improves long-term survival. 1, 2, 3

Treatment Algorithm Based on Disease Severity and Organ Involvement

Mild SLE (without major organ involvement)

• First-line: Hydroxychloroquine monotherapy (200-400 mg/day)

  • May be sufficient for mild disease without major organ involvement 4
  • Helps prevent disease progression and flares
  • Associated with significant reduction in mortality 3

• Adjunct therapy (as needed for symptom control):

  • NSAIDs for arthralgia/arthritis (short-term use)
  • Topical steroids for cutaneous manifestations
  • Low-dose oral glucocorticoids (≤10 mg/day prednisone) for temporary symptom control

Moderate to Severe SLE (with organ involvement)

For Lupus Nephritis Class III, IV, or V:

1. Induction therapy:

   • Mycophenolic acid (MPA) - target dose of mycophenolate mofetil (MMF) 3 g/day for 6 months 5, 1
   • OR low-dose intravenous cyclophosphamide (total dose 3 g over 3 months) 5
   • PLUS glucocorticoids:
     • Three consecutive pulses of IV methylprednisolone 500-750 mg
     • Followed by oral prednisone 0.5 mg/kg/day for 4 weeks
     • Taper to ≤10 mg/day by 4-6 months 5, 1
   • PLUS hydroxychloroquine (200-400 mg/day) 1, 2, 3

2. For patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents, fibrinoid necrosis):

   • Consider higher doses of cyclophosphamide (0.75-1 g/m² monthly for 6 months) 5

For Pure Class V Nephritis with Nephrotic-Range Proteinuria:

• MPA (MMF target dose 3 g/day for 6 months)
• PLUS oral prednisone (0.5 mg/kg/day)
• PLUS hydroxychloroquine (200-400 mg/day) 5, 1
• Alternative options: cyclophosphamide, calcineurin inhibitors, or rituximab 5

Special Considerations

Alternative Immunosuppressants

• Azathioprine (2 mg/kg/day) may be considered as an alternative to MPA or cyclophosphamide in:
  • Patients without adverse prognostic factors
  • When MPA/cyclophosphamide are contraindicated, not tolerated, or unavailable
  • When pregnancy is contemplated (switch at least 3 months prior to conception) 5, 1
  • Note: Azathioprine is associated with a higher flare risk 5

Adjunct Treatments

• ACE inhibitors or ARBs for patients with proteinuria or hypertension 5, 1
• Statins for persistent dyslipidemia (target LDL <100 mg/dL) 5
• Calcium and vitamin D supplementation 5, 1
• Immunizations with non-live vaccines 5
• Consider anticoagulation in nephrotic syndrome with serum albumin <20 g/L, especially with anti-phospholipid antibodies 5

Monitoring and Follow-up

• Initial monitoring every 2-4 weeks for first 2-4 months after diagnosis or flare 5
• Regular assessment of:
  • Body weight and blood pressure
  • Serum creatinine, eGFR, and albumin
  • Proteinuria and urinary sediment
  • Complement levels (C3, C4)
  • Anti-dsDNA antibody levels
  • Complete blood count 5, 1
• Ophthalmologic exams for hydroxychloroquine toxicity monitoring 1

Treatment Goals

• Complete renal response: UPCR <50 mg/mmol and normal/near-normal renal function
• Partial renal response: ≥50% reduction in proteinuria to subnephrotic levels with normal/near-normal renal function
• Target achievement: partial response by 6 months, complete response by 12 months 5, 1

Common Pitfalls and Caveats

• Do not discontinue hydroxychloroquine during pregnancy - it is safe and reduces flare risk 1
• Do not abruptly discontinue hydroxychloroquine - when reducing, decrease by no more than 600 mg per week 6
• Do not delay treatment for lupus nephritis - early intervention improves outcomes
• Avoid prolonged high-dose glucocorticoids - aim to taper to ≤10 mg/day by 4-6 months 5, 1
• Monitor for hydroxychloroquine retinal toxicity with regular ophthalmologic exams 1