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

Treatment of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine (200-400 mg daily) is the cornerstone medication for all SLE patients and should be initiated in all patients unless contraindicated. 1, 2

First-Line Treatment Approach

• Hydroxychloroquine (HCQ):

  • Dosage: 200-400 mg daily with food or milk
  • Benefits: Prevents flares, reduces organ damage, improves survival rates, and has cardiovascular protective effects 1, 3
  • Monitoring: Baseline and periodic ophthalmologic examinations to screen for retinal toxicity 1
  • Note: If hypersensitivity reactions occur, consider desensitization protocol rather than discontinuation 4

• Glucocorticoids:

  • For active disease: Initial low-to-moderate doses (0.25-0.5 mg/kg/day) 1
  • Target: Lowest effective dose (≤5 mg/day) for shortest duration possible 1
  • Taper: As quickly as clinically feasible to maintenance dose of ≤7.5 mg/day 1
  • Consider complete discontinuation after ≥12 months of complete clinical response 1

Treatment Based on Disease Manifestations

Mild to Moderate Disease

• Continue HCQ as baseline therapy
• Add immunomodulators based on predominant manifestations:
  • Musculoskeletal manifestations: Consider methotrexate or leflunomide 1
  • Milder systemic disease: Consider azathioprine 1

Moderate to Severe Disease

• Renal involvement:

  • Mycophenolate mofetil (1-3 g/day in divided doses) 1, 3
  • For Class III/IV lupus nephritis: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide 1
  • For Class V lupus nephritis: Prednisone with mycophenolate mofetil 1
  • Belimumab is FDA-approved for active lupus nephritis in patients ≥5 years receiving standard therapy 5, 3
  • Voclosporin is FDA-approved for lupus nephritis 3

• Hematological manifestations:

  • Acute manifestations: Prednisone 0.5-1 mg/kg/day for moderate cases; methylprednisolone pulses for severe cases 1
  • Refractory cases: Consider rituximab (375 mg/m² weekly for 4 weeks or 1000 mg on days 0 and 14) 1

• Active SLE without severe CNS involvement:

  • Belimumab is FDA-approved for patients ≥5 years with active SLE receiving standard therapy 5, 3
  • Anifrolumab is FDA-approved for active SLE 3

Disease Activity Assessment and Monitoring

• Use SLEDAI-2K to measure disease activity (scores: 0=remission, 1-5=mild, 6-10=moderate, >10=high) 1

• Monitor disease activity:

  • Every 2-4 weeks for first 2-4 months after diagnosis or flare
  • Then according to response
  • Lifelong monitoring at least every 3-6 months 1

• Laboratory monitoring:

  • Complete blood count: Every 1-3 months during active disease
  • Anti-dsDNA antibodies and complement levels (C3, C4): To assess disease activity
  • Renal function tests and urinalysis: To detect early kidney involvement 1

Important Adjunctive Measures

• Cardiovascular risk management:

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

• Infection prevention:

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

• Bone health:

  • Osteoporosis prophylaxis with calcium and vitamin D 1

• Lifestyle modifications:

  • Sun protection and UV light avoidance
  • Aerobic exercise programs to reduce fatigue and depressive symptoms
  • Psychosocial interventions to improve quality of life 1

Cautions and Pitfalls

• HCQ daily doses exceeding 5 mg/kg increase the risk of retinopathy 2
• Belimumab is not recommended for severe active CNS lupus 5
• Do not crush or divide HCQ tablets; administer with food or milk 2
• Avoid abrupt discontinuation of medications during remission; taper gradually
• Remember that SLE treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to both disease and treatment toxicity 3

Early intervention with hydroxychloroquine may delay disease onset and progression, highlighting the importance of prompt initiation of therapy 6.