What are the treatment options for lupus?

Treatment Options for Lupus

For patients with systemic lupus erythematosus (SLE), treatment should include antimalarials as the foundation, with the addition of glucocorticoids, immunosuppressants, and biologics based on disease severity and organ involvement. 1

First-Line Treatment

• Hydroxychloroquine (200-400 mg daily) is indicated for all lupus patients and should be used unless contraindicated, as it reduces disease activity, flares, and mortality 2, 3
• Glucocorticoids are used for active disease, with dosing based on severity:
  • For mild-moderate disease: Reduced-dose scheme starting at 0.5-0.6 mg/kg/day (max 40 mg) with rapid taper to ≤7.5 mg/day by 4-6 months 4
  • For severe disease: Consider initial IV methylprednisolone pulses (250-500 mg/day for up to 3 days) followed by oral prednisone 4
• NSAIDs may be used for musculoskeletal symptoms, serositis, and headache, but require close monitoring due to increased risk of renal, hepatic, and allergic reactions in lupus patients 5, 6, 7

Treatment Based on Organ Involvement

Lupus Nephritis (Class III/IV)

• Initial therapy should include glucocorticoids plus one of the following: 4
  • Mycophenolic acid analogs (MPAA)
  • Low-dose intravenous cyclophosphamide
  • Belimumab with either MPAA or low-dose cyclophosphamide
  • MPAA with a calcineurin inhibitor (when eGFR >45 ml/min/1.73m²)
• Maintenance therapy: 4, 8
  • MPAA (mycophenolate mofetil 750-1000 mg twice daily) for at least 36 months
  • Azathioprine (2 mg/kg/day) if MPAA is not tolerated or pregnancy is planned

Class V Lupus Nephritis

• Mycophenolate mofetil (target dose 3 g/day for 6 months) with oral prednisone (0.5 mg/kg/day) 4
• Alternative options: cyclophosphamide, calcineurin inhibitors (cyclosporine, tacrolimus), or rituximab 4

Cutaneous Lupus

• Topical glucocorticoids and calcineurin inhibitors for localized manifestations 1
• For widespread or severe disease, add short-term systemic glucocorticoids 1
• For refractory cases, consider methotrexate, retinoids, dapsone, or mycophenolate mofetil 1, 8

Biologic Therapies for Refractory Disease

• Belimumab is FDA-approved for active SLE and lupus nephritis, particularly beneficial for patients with repeated kidney flares 8, 9
• Rituximab should be considered for patients with persistent disease activity or inadequate response to standard therapies 4, 8
• Anifrolumab is FDA-approved for active SLE 3, 10

Adjunctive Therapies

• Photoprotection with broad-spectrum sunscreen and limited UV exposure 4, 1
• Calcium and vitamin D supplementation for bone health 4
• Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for proteinuria or hypertension 4
• Statins for persistent dyslipidemia 4
• Low-dose aspirin for patients with antiphospholipid antibodies 4, 1

Monitoring Treatment Response

• Regular monitoring of disease activity with clinical assessment and laboratory tests (complete blood count, serum creatinine, proteinuria, urine sediment, C3, C4, anti-dsDNA) 4, 1
• For lupus nephritis, complete response is defined as reduction in proteinuria <0.5 g/g with stable or improved kidney function within 6-12 months 4, 8
• Consider switching therapy if no improvement within 3-4 months or no partial response after 6-12 months 8

Important Considerations

• Minimize glucocorticoid exposure to reduce adverse effects (target <7.5 mg/day prednisone for maintenance) 4, 1
• Screen for and manage comorbidities: infections, cardiovascular disease, osteoporosis, and malignancies 4, 1
• Assess for tuberculosis, hepatitis B/C, and HIV before initiating immunosuppressive therapy 4
• Consider Pneumocystis jirovecii prophylaxis for patients on significant immunosuppression 4
• Limit lifetime cyclophosphamide exposure to <36 g to reduce malignancy risk 4