What are the first-line medications for lupus?

First-Line Medications for Lupus

Hydroxychloroquine is recommended as the first-line medication for all patients with systemic lupus erythematosus (SLE), regardless of disease severity or organ involvement. 1

Treatment Algorithm for Lupus

Step 1: Baseline Therapy for All Lupus Patients

• Hydroxychloroquine should be prescribed for all lupus patients at a dose not exceeding 5 mg/kg real body weight 1
• Ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1
• Hydroxychloroquine has been shown to improve outcomes by reducing renal flares and limiting accrual of renal and cardiovascular damage 1

Step 2: Additional First-Line Therapies Based on Disease Severity and Organ Involvement

For Mild Disease:

• Hydroxychloroquine alone may be sufficient for mild disease 1
• Low-dose glucocorticoids (prednisone <7.5 mg/day) may be added for symptom control 1

For Moderate to Severe Disease:

• Glucocorticoids are added at doses dependent on disease severity 1
  • Pulses of intravenous methylprednisolone (250-1000 mg/day for 1-3 days) may be used initially 1
  • Oral prednisone should be minimized to less than 7.5 mg/day for chronic maintenance 1
• Immunomodulatory agents should be promptly initiated to expedite tapering/discontinuation of glucocorticoids 1
  • Methotrexate for predominant skin/joint manifestations 1
  • Azathioprine as a steroid-sparing agent 1
  • Mycophenolate mofetil for various manifestations including lupus nephritis 1

For Organ-Threatening Disease:

• Immunosuppressive agents should be included in initial therapy 1
• For lupus nephritis:
  • Mycophenolate mofetil or low-dose intravenous cyclophosphamide are recommended as initial treatment due to best efficacy/toxicity ratio 1
  • For high-risk patients (reduced GFR, fibrous crescents, fibrinoid necrosis), high-dose intravenous cyclophosphamide can be used 1
• For severe neuropsychiatric manifestations:
  • Glucocorticoids and immunosuppressive agents for inflammatory manifestations 1
  • Antiplatelet/anticoagulants for atherothrombotic/antiphospholipid-related manifestations 1

Special Considerations for Specific Manifestations

Cutaneous Lupus:

• First-line treatment includes topical agents (glucocorticoids, calcineurin inhibitors), antimalarials (hydroxychloroquine, quinacrine), and/or systemic glucocorticoids 1
• Hydroxychloroquine at 400 mg/day is effective for most cutaneous lupus patients (50%-97% effectiveness) 2

Hematological Manifestations:

• Acute treatment of lupus thrombocytopenia includes high-dose glucocorticoids and/or intravenous immunoglobulin G 1
• For maintenance, immunosuppressive agents such as mycophenolate, azathioprine, or cyclosporine can be used 1

Renal Disease:

• Early recognition and diagnostic renal biopsy are essential 1
• Mycophenolate or low-dose intravenous cyclophosphamide with glucocorticoids are recommended as initial treatment 1
• Maintenance therapy should use mycophenolate or azathioprine 1

Treatment Monitoring and Adjustments

• Regular monitoring of disease activity is essential, with visits scheduled every 2-4 weeks for the first 2-4 months after diagnosis or flare 1
• Assessment should include body weight, blood pressure, serum creatinine, eGFR, serum albumin, proteinuria, urinary sediment, complement levels, and anti-dsDNA antibody levels 1
• Long-term follow-up should continue at least every 3-6 months 1

Common Pitfalls and Caveats

• Hydroxychloroquine dosing should not exceed 5 mg/kg real body weight to minimize risk of retinopathy 1
• Glucocorticoids should be minimized for chronic maintenance to less than 7.5 mg/day and withdrawn when possible 1
• Patients should be assessed for antiphospholipid antibody status, infectious disease risk, and cardiovascular risk factors 1
• Medication adherence is critical; hydroxychloroquine is often underprescribed or discontinued inappropriately 3
• Patients often have symptoms unexplained by lupus that require careful evaluation 4

Emerging Therapies

• For patients with inadequate response to standard therapy, belimumab should be considered as add-on treatment 1
• In organ-threatening disease refractory to standard immunosuppressives, rituximab can be considered 1
• Triple immunosuppressive regimens (belimumab with glucocorticoids and either mycophenolate or reduced-dose cyclophosphamide) may benefit patients with repeated kidney flares 1