What are the first-line treatments for lupus?

First-Line Treatments for Lupus

Hydroxychloroquine (HCQ) is the cornerstone first-line treatment for all patients with systemic lupus erythematosus (SLE) and should be prescribed at a dose not exceeding 5 mg/kg real body weight. 1

General Treatment Approach

The treatment of lupus follows a step-wise approach based on disease severity and organ involvement:

1. Antimalarial Therapy

• Hydroxychloroquine (HCQ):
  • Recommended for ALL lupus patients regardless of disease severity
  • Dosage: 200-400 mg daily (not exceeding 5 mg/kg real body weight) 1, 2
  • Benefits: Reduces disease flares, limits organ damage, improves survival
  • Monitoring: Baseline ophthalmologic exam, then after 5 years and yearly thereafter 1

2. Glucocorticoids (GC)

• Used based on disease severity and organ involvement 1
• Dosing strategies:
  • Pulse IV methylprednisolone (250-1000 mg/day for 1-3 days) for acute severe disease 1
  • Oral prednisone: Start at 0.5-1.0 mg/kg/day (maximum 80 mg) with tapering
  • Target: Minimize to <7.5 mg/day for chronic maintenance and withdraw when possible 1
  • Early initiation of immunomodulatory agents can expedite GC tapering 1

3. Immunosuppressive/Immunomodulatory Agents

For patients not responding to HCQ alone or requiring high-dose GC:

• Methotrexate: First choice for predominant arthritis 1, 3
• Azathioprine: Alternative for non-organ threatening disease 1
• Mycophenolate mofetil (MMF): Effective for various manifestations, especially lupus nephritis 1

Organ-Specific First-Line Treatments

Cutaneous Lupus

1. Topical agents (glucocorticoids, calcineurin inhibitors) 1
2. Antimalarials (HCQ, quinacrine) 1
3. Systemic glucocorticoids if needed 1
4. For refractory cases: methotrexate, retinoids, dapsone, or mycophenolate 1

Lupus Nephritis

For Class III/IV lupus nephritis:

1. Glucocorticoids plus ONE of the following: 1
   • Mycophenolic acid analogs (MMF 3 g/day) 1
   • Low-dose IV cyclophosphamide (500 mg every 2 weeks for 6 doses) 1
   • Belimumab plus either MMF or low-dose cyclophosphamide 1
   • MMF plus calcineurin inhibitor (when eGFR >45 ml/min/1.73m²) 1

Neuropsychiatric Lupus

• For inflammatory manifestations: Glucocorticoids plus immunosuppressive agents 1
• For thrombotic/ischemic manifestations: Antiplatelet/anticoagulant therapy 1

Hematologic Manifestations

• Acute thrombocytopenia: High-dose glucocorticoids (including IV pulses) and/or IVIG 1
• Maintenance: Mycophenolate, azathioprine, or cyclosporine 1
• Refractory cases: Rituximab or cyclophosphamide 1

Adjunctive Treatments

• ACE inhibitors or ARBs for proteinuria or hypertension 1
• Statins for dyslipidemia 1
• Calcium and vitamin D supplementation 1
• Vaccinations (non-live) 1
• Sun protection and broad-spectrum sunscreen 1

Common Pitfalls and Caveats

1. Underutilization of HCQ: Many patients are not prescribed or are non-adherent to HCQ despite its proven benefits in reducing flares and damage.

2. Overreliance on glucocorticoids: Long-term high-dose steroids cause significant morbidity. Early introduction of steroid-sparing agents is crucial.

3. Inadequate monitoring: Regular assessment of disease activity, medication side effects, and preventive care is essential.

4. Delayed treatment of nephritis: Early recognition and prompt treatment of renal involvement is critical for preserving kidney function.

5. Pregnancy considerations: Some medications (MMF, cyclophosphamide) are contraindicated in pregnancy. For women planning pregnancy, switch from MMF to azathioprine at least 3 months before conception 1.

6. Infection risk: Assess for infection risk factors and consider prophylaxis when appropriate, especially with more intensive immunosuppression.

The treatment approach should be adjusted based on disease severity, organ involvement, and response to therapy, with the ultimate goals of achieving disease remission, preventing flares, minimizing glucocorticoid exposure, and preserving organ function.