What are the treatment options for managing Systemic Lupus Erythematosus (SLE) relapses?

Treatment of SLE Relapses

For moderate to severe SLE flares, initiate induction therapy with intravenous methylprednisolone pulses combined with immunosuppressive agents, followed by maintenance therapy to prevent recurrence. 1

Immediate Management of Acute Flares

Glucocorticoid Induction Therapy

• Administer intravenous methylprednisolone pulse therapy (typically 500-1000 mg daily for 3 days) for moderate to severe flares, which provides immediate therapeutic effect and enables lower starting doses of oral glucocorticoids 2
• Follow with oral prednisone 0.5-1 mg/kg/day depending on severity, then aggressively taper 2
• The goal is to minimize chronic glucocorticoid exposure to less than 7.5 mg/day and withdraw when possible to prevent organ damage 2

Immunosuppressive Induction

• For severe organ-threatening flares (renal, cardiopulmonary, neuropsychiatric): Combine pulse methylprednisolone with cyclophosphamide 2
• For lupus nephritis flares: Use mycophenolate mofetil or low-dose cyclophosphamide as induction therapy 2
• For hematological flares with significant thrombocytopenia: Initial pulse IV methylprednisolone followed by moderate/high-dose glucocorticoids combined with immunosuppressive agents 2

Maintenance Therapy to Prevent Recurrence

Approximately one-third of patients flare after achieving remission, making maintenance therapy critical 1

First-Line Maintenance Options

• Mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 2
• Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 2
• Hydroxychloroquine must be continued in all patients unless contraindicated, as it reduces disease activity, prevents flares, and improves survival 2

Monitoring for Early Flare Detection

• Use validated activity indices (BILAG, ECLAM, or SLEDAI) at each visit 1
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment regularly 2
• New clinical manifestations (skin, anemia, lymphopenia, thrombocytopenia) and anti-C1q titers, anti-dsDNA, low serum C3/C4 correlate with disease severity and can predict future flares 1

Important caveat: Intensification of therapy based on serological activity alone (especially rising anti-dsDNA titers) risks overtreating patients, though one RCT showed it prevents relapses 1

Biologic Therapies for Refractory or Recurrent Flares

FDA-Approved Options

• Belimumab is approved for active extrarenal SLE in patients receiving standard therapy and for active lupus nephritis 2, 3
  • Intravenous dosing: 10 mg/kg at 2-week intervals for first 3 doses, then 4-week intervals 3
  • Subcutaneous dosing for adults: 200 mg once weekly 3
• Anifrolumab for moderate-to-severe extrarenal SLE 2
• Voclosporin for lupus nephritis 2

Off-Label Consideration

• Rituximab may be considered for refractory cases, particularly hematological manifestations, with small trials suggesting up to 50% of cyclophosphamide-refractory patients respond 1, 2

Organ-Specific Flare Management

Lupus Nephritis Flares

• Kidney biopsy is essential before initiating therapy 2
• Target at least partial remission within 6-12 months (defined as improvement in serum creatinine and reduction of proteinuria to <1 g/day) 1
• Failure to achieve significant response by 6 months should prompt discussion for intensification of therapy 1
• Remission can be induced again in a substantial percentage of patients experiencing lupus nephritis flares 4

Neuropsychiatric Flares

• For inflammatory/immune-mediated mechanisms: High-dose intravenous methylprednisolone plus cyclophosphamide 2
• For thrombotic/embolic mechanisms: Anticoagulation with warfarin 2

Cutaneous Flares

• Topical glucocorticoids and hydroxychloroquine as first-line 2
• Photoprotection with sunscreens prevents cutaneous flares 2

Critical Pitfalls to Avoid

• Do not delay kidney biopsy before treating lupus nephritis flares, as this leads to suboptimal therapy selection 2
• Avoid prolonged high-dose glucocorticoids beyond what is necessary for acute control, as chronic exposure causes significant organ damage 2
• Do not discontinue hydroxychloroquine during flares unless absolutely contraindicated, as it is the cornerstone of preventing future flares 2
• Monitor for infections closely, as SLE patients have a 5-fold increased mortality risk, with infections being a major contributor 5, 2

Adjunctive Measures During Flares

• Consider low-dose aspirin in patients receiving corticosteroids, those with antiphospholipid antibodies, or those with cardiovascular risk factors 2
• Ensure calcium and vitamin D supplementation for all patients on glucocorticoids 2
• Consider prophylactic premedication for infusion reactions when using belimumab 3