What are the treatment options for lupus?

Treatment Options for Lupus

The treatment of systemic lupus erythematosus (SLE) should be tailored to disease severity, with antimalarials (hydroxychloroquine) forming the cornerstone of therapy for all patients, supplemented by glucocorticoids and/or immunosuppressive agents based on organ involvement and disease activity. 1, 2

First-Line Therapy

• Hydroxychloroquine (200-400 mg daily) is indicated for all SLE patients regardless of disease severity or organ involvement, as it reduces disease activity, prevents flares, and improves survival 3, 2
• Glucocorticoids are used for active disease, with dosing dependent on severity:
  • For mild-moderate disease: low-dose prednisone (≤10 mg/day) 1
  • For severe or organ-threatening disease: higher doses (0.5-1 mg/kg/day) or intravenous methylprednisolone pulses (250-1000 mg for 1-3 days) 4
  • Aim for the lowest effective dose with gradual tapering to minimize long-term toxicity 1
• NSAIDs may be used judiciously for short periods in patients with low risk for complications, primarily for musculoskeletal symptoms 1, 5

Treatment Based on Organ Involvement

Skin Disease

• First-line: Topical agents (glucocorticoids, calcineurin inhibitors), antimalarials, and/or systemic glucocorticoids 1
• For refractory cases: Methotrexate, retinoids, dapsone, or mycophenolate 1

Musculoskeletal Disease

• First-line: Antimalarials plus low-dose glucocorticoids 1, 6
• For refractory arthritis: Methotrexate as the preferred agent, followed by mycophenolate mofetil or azathioprine 6

Lupus Nephritis (Classes III/IV)

• Initial therapy with glucocorticoids plus one of the following 1:
  • Mycophenolic acid analogs (MMF 2-3 g/day or equivalent) 1
  • Low-dose intravenous cyclophosphamide (Euro-Lupus regimen) 1
  • Belimumab plus either mycophenolate or cyclophosphamide 1
  • Mycophenolate plus calcineurin inhibitor (when eGFR >45 ml/min/1.73m²) 1
• Maintenance therapy with mycophenolate (preferred) or azathioprine for at least 36 months 1

Neuropsychiatric Lupus

• Distinguish inflammatory from thrombotic/ischemic manifestations through comprehensive evaluation 1
• For inflammatory manifestations (optic neuritis, acute confusional state, neuropathy, psychosis, myelitis): Immunosuppressive therapy with glucocorticoids and cyclophosphamide 1
• For thrombotic/ischemic manifestations associated with antiphospholipid antibodies: Antiplatelet/anticoagulant therapy 1

Hematological Disease

• For acute thrombocytopenia: High-dose glucocorticoids and/or intravenous immunoglobulin 1
• For maintenance: Mycophenolate, azathioprine, or cyclosporine 1
• For refractory cases: Rituximab or cyclophosphamide 1

Biologic Therapies

• Belimumab is recommended for patients with inadequate response to standard therapy (persistent disease activity despite hydroxychloroquine and immunosuppressants) 1, 7
• Rituximab can be considered for organ-threatening disease refractory to standard immunosuppressives 1, 6
• Anifrolumab is a newer FDA-approved option for active SLE 2

Adjunctive Therapies

• Photoprotection for patients with skin manifestations 1
• Lifestyle modifications including smoking cessation, weight control, and exercise 1
• Cardiovascular risk management with statins, antihypertensives (especially ACE inhibitors), and low-dose aspirin when indicated 1
• Bone health with calcium/vitamin D supplementation and bisphosphonates when appropriate 1
• Infection prevention through appropriate vaccination and consideration of antimicrobial prophylaxis during intensive immunosuppression 1

Treatment Goals and Monitoring

• Aim for remission or low disease activity in all organ systems 4
• Monitor disease activity using validated indices, complement levels (C3, C4), and anti-dsDNA antibodies 1, 4
• Regular screening for treatment-related complications and comorbidities (infections, cardiovascular disease, osteoporosis) 1, 2

Common Pitfalls and Considerations

• Hydroxychloroquine non-adherence is common but detrimental; emphasize its importance for long-term outcomes and mortality reduction 2
• Excessive glucocorticoid exposure increases damage accrual; use steroid-sparing agents early 1, 4
• Pregnancy planning requires medication adjustments; hydroxychloroquine should be continued, but mycophenolate and cyclophosphamide must be discontinued 1
• Infection risk increases with immunosuppression; screen for latent infections before initiating therapy 1
• Renal function monitoring is essential as kidney involvement affects approximately 40% of patients and can lead to end-stage kidney disease 2