What are the treatment options for Systemic Lupus Erythematosus (SLE)?

Treatment Options for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be administered to every patient with SLE regardless of disease severity or organ involvement as the cornerstone medication. 1, 2, 3

First-Line Therapy

• Hydroxychloroquine (HCQ):
  • Dosage: 200-400 mg daily (single dose or divided doses) 1, 2
  • Benefits: Reduces disease activity, morbidity, and mortality 3
  • Monitoring: Baseline and periodic ophthalmologic examinations to screen for retinal toxicity 1
  • Can be continued during pregnancy 1

Disease Assessment and Monitoring

• Disease Activity Assessment:

  • Use SLEDAI-2K tool to measure disease activity (scores range from 0-105) 1
    • Score 0: Remission (maintain current treatment)
    • Score 1-5: Consider minor adjustments
    • Score 6-10: Intensify treatment
    • Score >10: Aggressive treatment

• Monitoring Schedule:

  • Every 2-4 weeks for first 2-4 months after diagnosis or flare
  • Then according to response
  • At least every 3-6 months for lifelong monitoring 1
  • Laboratory monitoring:
    • Complete blood count every 1-3 months during active disease
    • Anti-dsDNA antibodies and complement levels (C3, C4)
    • Renal function tests and urinalysis 1

Treatment Based on Disease Severity

Mild Disease (Predominantly Musculoskeletal/Cutaneous)

1. Hydroxychloroquine: 200-400 mg daily 1, 2
2. NSAIDs: For symptomatic relief 4
3. Low-dose Corticosteroids:
   • Prednisone 0.25-0.5 mg/kg/day (≤30 mg/day)
   • Use lowest effective dose for shortest duration possible 1
4. Consider: Methotrexate or leflunomide for predominant musculoskeletal manifestations 1

Moderate Disease

1. Continue Hydroxychloroquine
2. Corticosteroids:
   • Prednisone 0.5-1 mg/kg/day for moderate manifestations 1
   • Taper to lowest possible dose (target ≤7.5 mg/day) 1
3. Immunosuppressives:
   • Azathioprine for milder disease 1
   • Mycophenolate mofetil (1-3 g/day in divided doses) as corticosteroid-sparing agent 1
   • Methotrexate for predominant musculoskeletal disease 1

Severe Disease/Organ Involvement

1. Continue Hydroxychloroquine

2. High-dose Corticosteroids:

   • Methylprednisolone pulses for severe manifestations 1

3. Specific Organ Involvement:

   • Lupus Nephritis:
     • Class III/IV: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide 1
     • Class V: Prednisone with mycophenolate mofetil 1
     • High-risk: High-dose intravenous cyclophosphamide 1
   • Hematological manifestations:
     • Rituximab for refractory thrombocytopenia or hemolytic anemia (375 mg/m² weekly for 4 weeks or 1000 mg on days 0 and 14) 1

4. Biologic Agents:

   • Belimumab: FDA-approved for active SLE and lupus nephritis 5, 3
   • Anifrolumab: FDA-approved for active SLE 3, 6
   • Voclosporin: FDA-approved for lupus nephritis 3, 6

Maintenance Therapy

• Taper corticosteroids to lowest possible dose (≤7.5 mg/day) 1
• Consider complete discontinuation after ≥12 months of complete clinical response 1
• Continue hydroxychloroquine indefinitely 1, 3
• Maintain immunosuppressive therapy at appropriate dose based on disease activity

Supportive Care and Comorbidity Management

• Cardiovascular Risk Management:

  • Blood pressure control (target <130/80 mmHg)
  • Dyslipidemia management with statins (target LDL <100 mg/dl) 1

• Osteoporosis Prevention:

  • Calcium and vitamin D supplementation 1

• Infection Prevention:

  • Screen for HIV, HCV, HBV, and tuberculosis before starting immunosuppressive therapy 1
  • Administer inactivated vaccines when SLE is inactive, preferably before immunosuppressive therapy 1

• Photoprotection:

  • UV light avoidance to prevent flares 1

Common Pitfalls to Avoid

• Delaying hydroxychloroquine initiation
• Overreliance on glucocorticoids
• Inadequate monitoring of disease activity
• Ignoring drug toxicity
• Missing concurrent infections 1

Treatment Goals

The primary goal of treatment is to achieve remission or low disease activity while minimizing glucocorticoid use and preventing organ damage 1, 6. Regular monitoring and adjustment of therapy based on disease activity are essential for optimal outcomes.