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

Treatment Approach for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be prescribed for all SLE patients as the cornerstone of therapy at a dose not exceeding 5 mg/kg real body weight, due to its ability to reduce disease activity, prevent flares, and improve survival. 1

First-Line Treatment

• Hydroxychloroquine serves as the backbone of SLE treatment and should be prescribed for all patients unless contraindicated 1, 2
• Regular ophthalmological screening is essential: at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1
• Glucocorticoids can be used for acute flares with doses based on severity of organ involvement 1
  • For acute flares, pulses of intravenous methylprednisolone provide immediate therapeutic effect 1
  • For chronic maintenance, glucocorticoids should be minimized to less than 7.5 mg/day and, when possible, withdrawn to prevent organ damage 1, 3

Second-Line Treatment

• For patients not responding to hydroxychloroquine alone or unable to reduce glucocorticoids, add immunomodulating/immunosuppressive agents 1:
  • Methotrexate for skin and joint manifestations 1
  • Azathioprine for maintenance therapy (particularly suitable for women contemplating pregnancy) 1
  • Mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 1
  • Cyclophosphamide for severe organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) 1

Organ-Specific Treatment Approaches

Lupus Nephritis

• Kidney biopsy is essential for diagnosis and treatment planning 1
• Induction therapy options include mycophenolate mofetil and cyclophosphamide 1
• Low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy and lower gonadotoxicity 1
• Maintenance therapy includes mycophenolate mofetil or azathioprine 1
• Belimumab has been FDA-approved for active lupus nephritis 4, 5
• Voclosporin has been FDA-approved specifically for lupus nephritis 5

Neuropsychiatric Lupus (NPSLE)

• Treatment depends on the underlying pathophysiological mechanism 1:
  • For inflammatory mechanisms: glucocorticoids and/or immunosuppressive agents 1
  • For embolic/thrombotic/ischemic mechanisms: anticoagulant/antithrombotic treatment 1
  • When both mechanisms coexist: combination of immunosuppressive and anticoagulant/antithrombotic therapy 1

Hematological Manifestations

• For significant thrombocytopenia: moderate/high doses of glucocorticoids combined with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 3
• Initial therapy with pulses of IV methylprednisolone is recommended 3
• IVIG may be considered in the acute phase or with inadequate response to glucocorticoids 3
• For refractory cases: rituximab or cyclophosphamide 3

Pulmonary Manifestations

• For SLE-ILD, first-line therapy should include mycophenolate, azathioprine, rituximab, or cyclophosphamide 6
• For rapidly progressive ILD, pulse intravenous methylprednisolone is recommended as first-line treatment 6

Biologic Therapies

• Consider biologics for patients with inadequate response to standard therapy 1, 5
• FDA-approved biologics for SLE include:
  • Belimumab: approved for active SLE and lupus nephritis 4, 5
  • Anifrolumab: approved for active SLE 5
• Rituximab may be considered for refractory cases, particularly for hematological manifestations, though not FDA-approved specifically for SLE 1, 3

Monitoring and Prevention of Complications

• Regular monitoring of disease activity using validated indices is crucial 1, 6
• Assess and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 1
• In patients with antiphospholipid antibodies, low-dose aspirin may be considered for primary prevention of thrombosis 1
• The first five years after diagnosis are crucial for prognosis and preventing organ damage 7

Treatment Goals

• The primary goal is to achieve remission or low disease activity and prevent flares in all organs 6, 5
• Minimize glucocorticoid use to prevent organ damage 1, 7
• Early introduction of appropriate therapies may help prevent long-term organ damage 7

Common Pitfalls and Caveats

• Prolonged use of high-dose glucocorticoids (>7.5 mg/day prednisone equivalent) significantly increases risk of irreversible organ damage 3
• Non-adherence to hydroxychloroquine is associated with higher flare rates 3
• Carefully monitor for infections, which are a common complication of immunosuppressive therapy 6
• Splenectomy should be reserved only as a last resort for cases of severe, refractory thrombocytopenia 3