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

Treatment for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine is the cornerstone of SLE treatment and should be prescribed for all patients with SLE at a dose not exceeding 5 mg/kg real body weight, unless contraindicated. 1, 2, 3

First-Line Treatment

• Hydroxychloroquine (HCQ) serves as the foundation of SLE therapy for all patients, with proven benefits in reducing disease activity, preventing flares, and improving long-term outcomes 1, 2, 4
• The recommended dose is not to exceed 5 mg/kg real body weight, with many patients maintained effectively on 200 mg daily 1, 5
• Regular ophthalmological monitoring is required (baseline, after 5 years, and yearly thereafter) to detect retinal toxicity 2
• Glucocorticoids should be used at the lowest effective dose, with a target of less than 7.5 mg/day prednisone equivalent for maintenance, and rapid tapering when possible 1, 2

Treatment Based on Disease Severity

Mild to Moderate SLE (without major organ involvement)

• Hydroxychloroquine as baseline therapy 2, 4
• Low-dose glucocorticoids for symptom control (target <7.5 mg/day prednisone) 1, 5
• Consider methotrexate for predominant articular and cutaneous manifestations 2

Moderate to Severe SLE (with major organ involvement)

• Continue hydroxychloroquine as baseline therapy 1, 2
• Immunosuppressive agents should be initiated promptly to allow for glucocorticoid tapering 1:
  • Mycophenolate mofetil
  • Azathioprine
  • Methotrexate
• For persistently active or flaring disease despite standard therapy, consider add-on belimumab 1, 2, 6
• For organ-threatening, refractory disease, rituximab may be considered 1, 7
• Cyclophosphamide can be used for severe organ-threatening disease or as "rescue" therapy 7, 8

Lupus Nephritis

• Initial treatment with mycophenolate mofetil or low-dose intravenous cyclophosphamide combined with glucocorticoids 8, 2
• Consider combination therapy with mycophenolate mofetil and calcineurin inhibitors (especially tacrolimus) for nephrotic-range proteinuria 2
• Target at least partial remission (≥50% reduction in proteinuria to subnephrotic levels and serum creatinine within 10% from baseline) by 6–12 months 1

Acute Severe Manifestations

• For severe or organ-threatening manifestations, administer pulses of intravenous methylprednisolone (250-1000 mg per day for 1-3 days) 7, 8
• After acute control, transition to oral prednisone with tapering to <7.5 mg/day 1, 7

Treatment Targets and Monitoring

• The goal of treatment is to achieve remission or low disease activity in all organ systems 1, 2
• Low disease activity states (SLEDAI ≤3 on antimalarials, or SLEDAI ≤4, PGA≤1 with GC ≤7.5 mg) are acceptable targets when complete remission cannot be achieved 1
• Regular monitoring of disease activity using validated indices (BILAG, SLEDAI) 7, 2
• Monitor complement levels (C3, C4) and anti-dsDNA antibodies to assess disease activity 7, 2

Management of Comorbidities

• Screen all patients for antiphospholipid antibodies at diagnosis 1
• Assess for traditional and disease-related risk factors for cardiovascular disease 1
• Consider preventative strategies such as low-dose aspirin and/or lipid-lowering agents based on individual cardiovascular risk profile 1
• Screen for and prevent infections, which are common complications of immunosuppressive therapy 1, 2

Newer Treatment Options

• Belimumab is recommended for patients with persistently active or flaring disease despite standard therapy 2, 6
• Anifrolumab and voclosporin are newer FDA-approved options for SLE and lupus nephritis, respectively 4, 9