What is the initial treatment for a patient with systemic lupus erythematosus (SLE)?

Treatment for Systemic Lupus Erythematosus

Foundation Therapy: Universal for All Patients

All patients with SLE must receive hydroxychloroquine at ≤5 mg/kg real body weight unless absolutely contraindicated, as this reduces disease activity, prevents flares, improves survival, and reduces mortality. 1, 2, 3

• Hydroxychloroquine is the cornerstone of therapy and should never be discontinued without specific contraindication 4, 1
• Ophthalmological screening is mandatory at baseline, after 5 years, then yearly thereafter using visual fields examination and/or spectral domain-optical coherence tomography to monitor for retinal toxicity 1
• Add photoprotection with sunscreens to prevent cutaneous flares 4, 5
• Provide calcium and vitamin D supplementation for patients on glucocorticoids 1
• Consider low-dose aspirin for patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1, 5

Glucocorticoid Strategy: Minimize and Taper Aggressively

Glucocorticoids should be prescribed at the lowest possible dose and for the shortest period of time, with a chronic maintenance goal of <7.5 mg/day prednisone equivalent and withdrawal when possible. 4, 1

• For acute flares or initial presentation, use intravenous methylprednisolone pulse therapy (250-1000 mg daily for 1-3 days) to provide immediate therapeutic effect and enable lower starting doses of oral glucocorticoids 1
• Taper aggressively to <7.5 mg/day prednisone equivalent to prevent irreversible organ damage 1
• Prompt initiation of immunomodulatory agents expedites glucocorticoid tapering and discontinuation 1

Immunosuppressive Therapy: Organ-Specific Selection

When patients fail to respond to hydroxychloroquine alone or in combination with glucocorticoids, or cannot taper glucocorticoids below acceptable doses, add immunosuppressive agents based on organ involvement. 1

For Musculoskeletal and Cutaneous Manifestations:

• Methotrexate is the preferred agent for skin and joint manifestations 1, 6
• For refractory cutaneous disease, use mycophenolate mofetil 5
• Topical glucocorticoids or calcineurin inhibitors for localized cutaneous lesions 5

For Lupus Nephritis (Class III/IV):

• Kidney biopsy is essential before initiating therapy 4, 1
• Induction therapy: Mycophenolate mofetil (first-line) or low-dose intravenous cyclophosphamide (Euro-Lupus regimen preferred over NIH high-dose regimen due to comparable efficacy and lower gonadotoxicity) 4, 1
• Combine with corticosteroids (intravenous methylprednisolone pulses followed by oral taper) 4
• Maintenance therapy: Mycophenolate mofetil or azathioprine 4, 1
• If worsening occurs during first 3 months (rising creatinine, worsening proteinuria), switch to alternative therapy or repeat kidney biopsy 4

For Severe Organ-Threatening Disease:

• Cyclophosphamide is reserved for severe organ-threatening or life-threatening SLE, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1
• Use intravenous dosing (NIH or Euro-Lupus regimen) rather than oral dosing due to lower cumulative doses and adverse event rates 4

For Maintenance Therapy:

• Azathioprine is particularly suitable for women contemplating pregnancy 1

Biologic Therapies: For Inadequate Response to Standard Therapy

When there is inadequate response to standard immunosuppression, residual disease activity, or frequent relapses, add biologic therapy. 1

• Belimumab (anti-BAFF antibody) is FDA-approved for active extrarenal SLE in patients ≥5 years receiving standard therapy, and for active lupus nephritis 7, 2
  • Intravenous dosing: 10 mg/kg at 2-week intervals for first 3 doses, then at 4-week intervals 7
  • Subcutaneous dosing for adults with SLE: 200 mg once weekly 7
  • For lupus nephritis: 400 mg (two 200-mg injections) once weekly for 4 doses, then 200 mg once weekly 7
• Anifrolumab (anti-type 1 interferon receptor) for moderate-to-severe extrarenal SLE 1, 2
• Voclosporin for lupus nephritis 1, 2
• Rituximab for organ-threatening disease refractory to or with intolerance/contraindications to standard immunosuppressive agents 1

Organ-Specific Protocols

Neuropsychiatric Lupus:

• Exclude infection aggressively before initiating immunosuppressive therapy 5
• For inflammatory/immune-mediated mechanisms: high-dose intravenous methylprednisolone plus cyclophosphamide 1
• For thrombotic/embolic mechanisms: anticoagulation with warfarin (target INR 2.0-3.0 for first venous thrombosis, 3.0-4.0 for arterial or recurrent thrombosis) 1

Hematological Manifestations:

• For significant thrombocytopenia: high-dose glucocorticoids (including intravenous methylprednisolone pulses) combined with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 1
• Intravenous immunoglobulin G may be considered in acute phase or with inadequate response to glucocorticoids 1
• For refractory cases: rituximab or cyclophosphamide 1

Monitoring and Comorbidity Prevention

Use validated disease activity indices (SLEDAI, BILAG, or ECLAM) at each visit to monitor lupus activity and detect flares. 1, 5

• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment at each visit 1, 5
• SLE patients have a 5-fold increased mortality risk; screen aggressively for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, avascular necrosis, and malignancies (especially non-Hodgkin lymphoma) 1, 5

Special Populations: Pregnancy

During pregnancy, use only prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin; avoid mycophenolate mofetil, cyclophosphamide, and methotrexate. 1, 5

• Pregnancy should be postponed for 6 months after withdrawal of bisphosphonates 1
• Patients with lupus nephritis and antiphospholipid antibodies require closer monitoring for preeclampsia 5

Critical Pitfalls to Avoid

• Never discontinue hydroxychloroquine unless there is a specific contraindication 4, 1
• Never assume fever is solely due to lupus activity without excluding infection first 5
• Never use prolonged high-dose glucocorticoids (>7.5 mg/day) as risks substantially increase above this threshold 1, 5
• Do not use oral cyclophosphamide when intravenous formulation is available due to higher cumulative doses and adverse events 4
• Live vaccines should not be given concurrently with belimumab or other immunosuppressive agents 7