What is the first-line treatment for Systemic Lupus Erythematosus (SLE)?

First-Line Treatment for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine is recommended as first-line treatment for all patients with SLE, regardless of disease severity or organ involvement, unless contraindicated. 1

Rationale for Hydroxychloroquine as First-Line Therapy

Hydroxychloroquine (HCQ) is the cornerstone of SLE management due to its multiple beneficial effects:

• Reduces disease activity and prevents flares 1
• Decreases damage accrual and improves long-term outcomes 2
• Reduces mortality in SLE patients 3
• Allows for lower glucocorticoid doses 2
• Provides cardioprotective and metabolic benefits 1, 2

The 2019 EULAR guidelines strongly recommend HCQ for all SLE patients, with level 1b/A evidence supporting this recommendation 1. This recommendation is consistent across multiple guidelines and is supported by the FDA-approved indication for HCQ in systemic lupus erythematosus 4.

Dosing Recommendations

• Maximum daily dose: 5 mg/kg real body weight 1
• Typical starting dose: 200-400 mg daily 2
• Regular ophthalmological screening is required: at baseline, after 5 years, and yearly thereafter 1

Treatment Algorithm for SLE

Step 1: First-Line Treatment for All SLE Patients

• Hydroxychloroquine for all patients (unless contraindicated)
• Add photo-protection measures for skin manifestations
• Implement lifestyle modifications (smoking cessation, weight control, exercise)
• Consider preventive measures for osteoporosis, cardiovascular disease, and infections

Step 2: For Patients with Mild to Moderate Disease Activity

If HCQ alone is insufficient:

• Add low-dose glucocorticoids (≤7.5 mg/day prednisone equivalent) for the shortest time possible 1
• Consider NSAIDs for short-term use in patients at low risk for complications 1

Step 3: For Patients with Inadequate Response or Moderate to Severe Disease

Add immunosuppressive agents based on organ involvement:

• For musculoskeletal manifestations: methotrexate, leflunomide, or azathioprine 1
• For skin disease: methotrexate, retinoids, dapsone, or mycophenolate 1
• For lupus nephritis: mycophenolate mofetil or cyclophosphamide 1

Step 4: For Refractory Disease

• Consider biologics: belimumab for active disease not responding to standard therapy 1, 3
• Rituximab may be considered for organ-threatening refractory disease 1

Important Considerations and Pitfalls

1. Non-adherence to HCQ: Blood level monitoring can help identify non-adherence, which is common and leads to worse outcomes 5

2. Retinal toxicity: The main serious adverse effect of HCQ, requiring regular ophthalmological screening. Risk increases with:

   • Duration of treatment (especially >5 years)
   • Higher daily doses
   • Renal impairment
   • Pre-existing retinal disease 1, 2

3. Pregnancy: HCQ should be continued during pregnancy and breastfeeding, as it is safe and may improve outcomes 1, 5

4. Delayed treatment: Early initiation of HCQ is crucial, as it may delay disease progression in individuals with positive antinuclear antibodies 2

5. Underutilization: Despite strong evidence supporting its use, HCQ remains underutilized in clinical practice 5

By following this treatment approach with hydroxychloroquine as the foundation of therapy, clinicians can significantly improve morbidity, mortality, and quality of life outcomes for patients with SLE.