What are the treatment options for lupus?

Treatment Options for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be considered the cornerstone of therapy for all patients with SLE, regardless of disease severity or organ involvement, unless contraindicated. 1, 2

First-Line Treatments

• Hydroxychloroquine is indicated for all SLE patients at a dose not exceeding 5 mg/kg real body weight, with regular ophthalmological screening at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1, 2
• Glucocorticoids can be used for disease flares, with the goal of using the lowest possible dose for the shortest period of time (ideally <7.5 mg/day prednisone equivalent) 3, 1
• For acute flares, pulses of intravenous methylprednisolone can provide immediate therapeutic effect and enable the use of lower starting doses of oral glucocorticoids 1
• Photoprotection is essential for patients with cutaneous manifestations 4

Second-Line Treatments

• In patients not responding to hydroxychloroquine alone or unable to reduce glucocorticoids to acceptable doses, immunomodulating/immunosuppressive agents should be added 1, 4
• Methotrexate is effective for skin and joint manifestations 1, 4
• Azathioprine is suitable for maintenance therapy, particularly for women contemplating pregnancy 1, 4
• Mycophenolate mofetil (MMF) is effective for renal and non-renal manifestations (except neuropsychiatric disease) 1, 4
• Cyclophosphamide is reserved for severe organ-threatening disease, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1, 3

Organ-Specific Treatment Approaches

Lupus Nephritis

• Kidney biopsy is essential for diagnosis and treatment planning for lupus nephritis 3, 1
• For class III/IV lupus nephritis, the KDIGO 2024 guidelines recommend three initial treatment options, each with strong recommendation (1B) 3:
  • Mycophenolic acid derivatives (MPAA) plus glucocorticoids
  • Intravenous cyclophosphamide plus glucocorticoids
  • Triple therapy with MPAA, glucocorticoids, and either a calcineurin inhibitor (voclosporin or tacrolimus) or belimumab 3
• For pure class V lupus nephritis with nephrotic-range proteinuria, mycophenolic acid plus glucocorticoids is recommended as initial treatment 3
• Maintenance therapy includes mycophenolate mofetil or azathioprine for at least 3 years 3

Neuropsychiatric Lupus

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

Hematological Manifestations

• For significant thrombocytopenia: moderate/high doses of glucocorticoids in combination with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 1
• For refractory cases: rituximab or cyclophosphamide 1

Biologic Therapies

• Belimumab is FDA-approved for active SLE and lupus nephritis, particularly effective in patients with high disease activity, positive autoantibodies, and on standard therapy 5, 6
• Rituximab may be considered for refractory cases, particularly for hematological manifestations 1
• Anifrolumab is FDA-approved for active SLE 6, 7
• Voclosporin is FDA-approved specifically for lupus nephritis 6, 7

Treatment Selection Considerations

• When choosing between belimumab and calcineurin inhibitors for triple therapy in lupus nephritis, consider 3:
  • Kidney function: Calcineurin inhibitors should be used cautiously if GFR <45 ml/min/1.73m²; belimumab may be used if GFR ≥30 ml/min/1.73m²
  • Proteinuria level: Calcineurin inhibitors may be especially effective with severe proteinuria; belimumab more effective with proteinuria <3g/day
  • Extrarenal lupus: Belimumab has proven efficacy for extrarenal manifestations
  • Pregnancy planning: Neither is recommended during pregnancy (consider tacrolimus instead of voclosporin if pregnancy is planned)

Monitoring and Prevention of Complications

• Regular monitoring of disease activity using validated indices is crucial 4
• Assess and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 4
• In patients with antiphospholipid antibodies, low-dose aspirin may be considered for primary prevention of thrombosis 4, 8
• NSAIDs can be used for musculoskeletal symptoms but require careful monitoring, especially in patients with lupus nephritis who are at increased risk for NSAID-induced acute renal failure 8, 9

Important Considerations

• The therapeutic goal should be to reach and maintain remission or low disease activity as soon as possible after diagnosis 3, 6
• Treatment should include comprehensive care addressing photoprotection, osteoporosis prevention, cardiovascular risk management, metabolic syndrome prevention, and infection prevention 3
• Pregnancy requires special consideration - prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin may be used, while mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided 4