What are the treatment options 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 unless contraindicated, at a dose not exceeding 5 mg/kg real body weight. 1, 2, 3

First-Line Treatment

• Hydroxychloroquine (HCQ) is recommended for all SLE patients as it reduces disease activity, prevents flares, improves survival, and serves as the foundation of therapy 1, 2, 3
• Regular ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1, 2
• Glucocorticoids (GC) can be used at doses and routes of administration depending on the type and severity of organ involvement 1, 2
• For acute flares, pulses of intravenous methylprednisolone (250-1000 mg per day for 1-3 days) provide immediate therapeutic effect and enable lower starting doses of oral GC 1
• For chronic maintenance treatment, GC should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn to prevent organ damage 1, 2

Second-Line Treatment

• In patients not responding to HCQ alone or in combination with GC, or unable to reduce GC below acceptable doses, immunomodulating/immunosuppressive agents should be added 1
• Options include:
  • Methotrexate - particularly effective for skin and joint manifestations 1, 2, 4
  • Azathioprine - suitable for maintenance therapy, particularly for women contemplating pregnancy 1, 2
  • Mycophenolate mofetil - effective for renal and non-renal manifestations (except neuropsychiatric disease) 1, 2
  • Cyclophosphamide - for severe organ-threatening or life-threatening SLE 1, 2

Organ-Specific Treatment Approaches

Lupus Nephritis

• Early recognition of renal involvement and diagnostic renal biopsy are essential for optimal outcomes 1
• Mycophenolate or low-dose intravenous cyclophosphamide are recommended as initial (induction) treatment 1
• For high-risk patients (reduced GFR, fibrous crescents, fibrinoid necrosis, tubular atrophy/interstitial fibrosis), high-dose intravenous cyclophosphamide can be considered 1
• For maintenance therapy, mycophenolate or azathioprine should be used 1
• In cases with incomplete renal response, mycophenolate may be combined with low-dose calcineurin inhibitors 1

Neuropsychiatric Lupus

• Treatment depends on the underlying pathophysiological mechanism 2
• For inflammatory mechanisms: glucocorticoids and/or immunosuppressive agents 1, 2
• For thrombotic/ischemic mechanisms: antiplatelet/anticoagulant therapy 1, 2

Skin Disease

• First-line treatment includes topical agents (glucocorticoids, calcineurin inhibitors), antimalarials, and/or systemic glucocorticoids 1, 5
• For non-responsive cases: methotrexate, retinoids, dapsone, or mycophenolate can be added 1, 5

Hematological Manifestations

• Acute treatment of thrombocytopenia includes high-dose glucocorticoids and/or intravenous immunoglobulin G 1
• For maintenance: mycophenolate, azathioprine, or cyclosporine 1
• Refractory cases can be treated with rituximab or cyclophosphamide 1

Biologic Therapies

• In patients with inadequate response to standard therapy (defined as residual disease activity not allowing tapering of glucocorticoids and/or frequent relapses), add-on treatment with belimumab should be considered 1, 6
• In organ-threatening disease refractory or with intolerance to standard immunosuppressive agents, rituximab can be considered 1, 6

Treatment Goals and Monitoring

• Treatment should aim at remission or low disease activity and prevention of flares in all organs 1, 2
• Regular monitoring of disease activity using validated indices is crucial to distinguish between active inflammation versus damage 2, 5
• Assess and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 2, 5

Special Considerations

• In patients with antiphospholipid antibodies, low-dose aspirin may be considered for primary prevention of thrombosis 2, 5
• During pregnancy, prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin may be used, while avoiding mycophenolate mofetil, cyclophosphamide, and methotrexate 5

Common Pitfalls to Avoid

• Prolonged use of high-dose glucocorticoids (>7.5 mg/day prednisone equivalent) increases risk of irreversible organ damage 1, 2
• Non-adherence to hydroxychloroquine is associated with higher flare rates and increased disease activity 2, 5
• Failure to recognize and treat comorbidities can significantly impact morbidity and mortality 2, 5