What is the recommended treatment for Systemic Lupus Erythematosus (SLE)?

Treatment of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine (HCQ) is the cornerstone of SLE treatment and should be prescribed to all SLE patients unless contraindicated, as it reduces disease activity, prevents flares, and improves long-term survival. 1, 2

First-Line Treatment

• Hydroxychloroquine (HCQ): Standard of care for all SLE patients

  • Reduces disease activity, flares, morbidity, and mortality
  • Recommended dose: ≤5 mg/kg/day based on actual body weight
  • Regular ophthalmologic monitoring required due to risk of retinal toxicity
  • Compatible with pregnancy and breastfeeding 2, 3, 4

• Glucocorticoids (GC): For active disease

  • Use lowest effective dose for shortest duration possible
  • Consider pulse IV methylprednisolone for severe flares
  • Aim to taper to ≤7.5 mg/day prednisolone or equivalent 2

Second-Line Treatment (Non-Organ Threatening Disease)

Add when HCQ alone is insufficient or for poor symptom control:

1. Methotrexate (MTX)

   • Stronger evidence than azathioprine for non-renal manifestations
   • Contraindicated during pregnancy 2

2. Azathioprine (AZA)

   • Compatible with pregnancy
   • Relatively safe profile 2

3. Mycophenolate mofetil (MMF)

   • Potent immunosuppressant for renal and non-renal lupus
   • Superior to AZA in achieving remission and reducing flares
   • Teratogenic (discontinue at least 6 weeks before conception) 2

4. Belimumab

   • FDA-approved for active SLE in patients receiving standard therapy
   • Not recommended for severe active CNS lupus 5, 3

Treatment of Specific Organ Involvement

Lupus Nephritis

1. Class III/IV (Proliferative) Nephritis:

   • Induction: IV methylprednisolone pulses followed by oral prednisone with either:
     • Mycophenolate mofetil (MMF) OR
     • Cyclophosphamide (CYC)
   • Maintenance: Lower dose prednisone plus MMF or AZA 6, 2

2. Class V (Membranous) Nephritis:

   • Prednisone with mycophenolate mofetil 6

3. High-risk features:

   • High-dose intravenous cyclophosphamide 6

4. Recently approved:

   • Belimumab: FDA-approved for active lupus nephritis 5
   • Voclosporin: FDA-approved for lupus nephritis 3

Neuropsychiatric SLE (NPSLE)

Treatment depends on underlying pathophysiology:

1. Inflammatory manifestations (optic neuritis, acute confusional state, neuropathy, psychosis, myelitis):

   • Glucocorticoids and immunosuppressive therapy
   • Cyclophosphamide for severe manifestations 2, 6

2. Thrombotic/ischemic manifestations:

   • Anticoagulant/antithrombotic therapy when antiphospholipid antibodies are present
   • Combination therapy may be considered when both mechanisms coexist 2, 6

Hematological Manifestations

1. Significant thrombocytopenia (platelets <30,000/mm³):

   • Moderate/high-dose GC + immunosuppressant (AZA, MMF, cyclosporine)
   • Consider IV immunoglobulin (IVIG) in acute phase
   • Rituximab for refractory cases 2

2. Autoimmune hemolytic anemia:

   • Treatment follows same principles as thrombocytopenia 2

Antiphospholipid Syndrome in SLE

• Primary prevention: Low-dose aspirin in SLE patients with antiphospholipid antibodies
• Secondary prevention: Long-term anticoagulation with oral anticoagulants
• Pregnancy: Combined unfractionated or low molecular weight heparin and aspirin 2, 6

Monitoring

• Regular assessment of disease activity using validated indices (SLEDAI, BILAG, SLAM)
• Annual assessment of damage using SLICC/ACR Damage Index
• Laboratory monitoring (more frequent during active disease or treatment changes)
• Regular screening for specific organ involvement and comorbidities 6

Treatment Pitfalls and Considerations

• Adherence monitoring: Blood HCQ concentration can identify non-adherence 7
• Pregnancy planning: MMF, CYC, and MTX must be avoided; HCQ, AZA, and low-dose aspirin are compatible 2
• Cardiovascular risk: HCQ has antithrombotic and metabolic effects that may improve cardiovascular outcomes 7, 4
• Cyclophosphamide caution: Use with care in women and men of fertile age due to gonadotoxicity 2
• CNS lupus: Belimumab not recommended for severe active CNS lupus 5

Preventive Measures

• Sun protection
• Vaccination (inactivated vaccines recommended; avoid live vaccines during immunosuppression)
• Cardiovascular risk factor control
• Osteoporosis prevention
• Lifestyle modifications (regular exercise, smoking cessation, weight control, stress management) 6