What is the initial treatment approach for a lupus flare-up?

Initial Treatment Approach for a Lupus Flare-Up

The initial treatment for a lupus flare-up should include glucocorticoids as the cornerstone therapy, along with appropriate immunosuppressive agents based on organ involvement and severity. 1

Glucocorticoid Therapy

• For severe or organ-threatening flares, intravenous methylprednisolone pulses (250-500 mg/day for up to 3 days) followed by oral prednisone is recommended 1
• Initial oral prednisone dosing should be based on severity 2:
  • High-dose: 0.8-1.0 mg/kg/day (maximum 80 mg)
  • Moderate-dose: 0.6-0.7 mg/kg/day (maximum 50 mg)
  • Reduced-dose: 0.5-0.6 mg/kg/day (maximum 40 mg)
• Aim to taper prednisone to ≤7.5 mg/day as quickly as possible following a structured tapering schedule 2, 1
• Triamcinolone injection may lead to more rapid response than oral methylprednisolone for mild/moderate flares 3

Immunosuppressive Therapy Options

For active lupus nephritis (Class III or IV), add one of the following to glucocorticoids 2:

• Mycophenolic acid analogs (MPAA): MMF 1.0-1.5 g twice daily or mycophenolic acid sodium 0.72-1.08 g twice daily 2
• Low-dose intravenous cyclophosphamide: 500 mg every 2 weeks for 6 doses 2
• Belimumab (10 mg/kg IV every 2 weeks for 3 doses then every 4 weeks) plus either MPAA or reduced-dose cyclophosphamide 2, 4
• Calcineurin inhibitor (voclosporin, tacrolimus, or cyclosporine) plus MPAA in patients with preserved kidney function (eGFR >45 ml/min/1.73m²) 2

Treatment Selection Based on Clinical Presentation

• For patients with lupus nephritis, MPAA-based regimen is preferred for those at high risk of infertility 2
• Intravenous cyclophosphamide can be used for patients who may have difficulty adhering to an oral regimen 2
• Calcineurin inhibitors are preferred for patients with nephrotic-range proteinuria and preserved kidney function 2
• Triple immunosuppressive regimen with belimumab is preferred for patients with repeated kidney flares or high risk for progression to kidney failure 2, 4
• Rituximab may be considered for patients with persistent disease activity or inadequate response to initial standard therapy 2

Maintenance Therapy

• After initial therapy, patients should be placed on MPAA for maintenance (MMF 750-1000 mg twice daily) 2
• Azathioprine is an alternative to MPAA for patients who don't tolerate MPAA, lack access to it, or are considering pregnancy 2
• The total duration of initial plus maintenance immunosuppression should be ≥36 months 2, 1
• Glucocorticoids should be tapered to the lowest possible dose during maintenance 2

Monitoring Response

• Complete response is defined as reduction in proteinuria <0.5 g/g with stable or improved kidney function 2
• Partial response is defined as reduction in proteinuria by at least 50% and to <3 g/g 2
• If the diagnosis of flare remains uncertain, a repeat kidney biopsy to assess disease activity versus chronic damage is important 2

Important Considerations and Pitfalls

• Hydroxychloroquine should be maintained in all patients with SLE (unless contraindicated) as it reduces mortality 1, 5
• Prolonged glucocorticoid exposure is associated with significant organ damage and morbidity 6, 7
• Low mycophenolic acid exposure is associated with increased risk of disease flares 2
• Patients with persistent anti-dsDNA antibodies have higher risk of flares and poorer long-term outcomes 8
• Abrupt withdrawal of glucocorticoids in patients on long-term therapy may lead to withdrawal symptoms that mimic disease flare 1
• Lupus flare treatment should be the same whether it's a new presentation or a relapse of previously controlled disease 2