What are the treatment options for lupus?

Treatment Options for Lupus

Hydroxychloroquine should be prescribed to all patients with systemic lupus erythematosus (SLE) unless contraindicated, as it reduces disease activity, prevents flares, and improves survival. 1

First-Line Therapy

• Hydroxychloroquine (HCQ): 200-400 mg daily (single dose or divided doses) 2
  • Essential for all SLE patients regardless of disease severity or organ involvement
  • Improves outcomes by reducing renal flares and limiting accrual of renal and cardiovascular damage 3
  • Continues during pregnancy to reduce flares and improve outcomes 1
  • Requires annual ophthalmological screening after 5 years of treatment 3

Treatment Based on Disease Severity and Organ Involvement

Mild SLE (Mucocutaneous, Musculoskeletal)

1. Hydroxychloroquine 200-400 mg daily
2. NSAIDs for short-term symptom control
3. Low-dose corticosteroids (≤10 mg/day prednisone) for flares 1, 4

Moderate to Severe SLE

Add one of the following immunosuppressive agents to hydroxychloroquine:

• Azathioprine: 2 mg/kg/day 3, 1

  • Good for maintenance therapy
  • Preferred when pregnancy is contemplated (switch from MMF at least 3 months before conception) 3

• Mycophenolate mofetil (MMF): 2-3 g/day 1

  • Preferred for maintenance therapy
  • Contraindicated during pregnancy 1

• Methotrexate: For refractory joint symptoms 4

Lupus Nephritis (Class III/IV)

For active Class III or IV lupus nephritis, treatment should include glucocorticoids plus one of the following regimens: 3

1. Mycophenolic acid analogs (MPAA):

   • MMF 1.0-1.5 g twice daily or mycophenolic acid sodium 0.72-1.08 g twice daily 3

2. Low-dose intravenous cyclophosphamide:

   • 500 mg every 2 weeks for 6 doses 3
   • Consider for patients with difficulty adhering to oral regimens 3
   • Minimize lifetime exposure to <36 g to reduce cancer risk 3

3. Belimumab plus either MPAA or low-dose cyclophosphamide:

   • Belimumab 10 mg/kg IV every 2 weeks for 3 doses, then every 4 weeks 3
   • Duration up to 2.5 years 3

4. MPAA plus calcineurin inhibitor (when eGFR >45 ml/min/1.73 m²):

   • Voclosporin 23.7 mg twice daily with MPAA 3
   • Alternative: cyclosporine or tacrolimus 3

Pure Class V Lupus Nephritis (Membranous)

• MMF (target dose 3 g/day for 6 months) with oral prednisone (0.5 mg/kg/day) 3
• Alternatives: cyclophosphamide, calcineurin inhibitors, or rituximab 3

Glucocorticoid Regimens

Initial therapy often includes:

• IV methylprednisolone 0.25-0.5 g/day for 1-3 days (based on severity) 3
• Followed by oral prednisone at 0.35-1.0 mg/kg/day (maximum 80 mg/day) 3
• Taper over months to maintenance dose (≤10 mg/day by 4-6 months) 3

A reduced-dose regimen should be considered when both kidney and extrarenal manifestations show satisfactory improvement 3

Treatment for Refractory Disease

For patients who fail treatment with one agent (lack of effect or adverse events):

• Switch from MMF to cyclophosphamide or vice versa 3
• Consider rituximab 3, 4
• Other options: intravenous immunoglobulin, calcineurin inhibitors 3, 4
• Newer biologics: belimumab, anifrolumab 5

Adjunctive Treatments

1. Cardiovascular and renal protection:

   • ACE inhibitors or ARBs for proteinuria or hypertension 3
   • Statins for dyslipidemia (target LDL <100 mg/dl) 3
   • SGLT2 inhibitors for stable patients with CKD 3

2. Infection prevention:

   • Screen for HBV, HCV, HIV, and TB 3
   • Consider Pneumocystis jirovecii prophylaxis 3
   • Non-live vaccines recommended 1

3. Bone health:

   • Calcium and vitamin D supplementation 3, 1
   • Bisphosphonates when appropriate 3, 1

4. Sun protection:

   • Broad-spectrum sunscreen 3
   • Limit ultraviolet light exposure 3, 1

5. Reproductive health:

   • Contraception counseling 3
   • Consider gonadotropin-releasing hormone agonists or gamete cryopreservation if using cyclophosphamide 3

Monitoring

• Regular assessment of disease activity using validated indices (SLEDAI, BILAG) 1
• Monitor serum creatinine, eGFR, proteinuria, urinary sediment, serum C3/C4, anti-dsDNA antibody levels, and complete blood count 3
• Schedule visits every 2-4 weeks for the first 2-4 months after diagnosis or flare, then every 3-6 months 3
• Consider repeat renal biopsy for worsening or refractory disease 3

Common Pitfalls to Avoid

1. Discontinuing hydroxychloroquine: Never stop HCQ during pregnancy or remission as it reduces flares and improves long-term outcomes 1

2. Prolonged high-dose corticosteroids: Aim to taper to ≤10 mg/day by 4-6 months to minimize side effects 3

3. Inadequate monitoring: Regular follow-up is essential to detect early signs of disease flare or treatment toxicity 3

4. Ignoring comorbidities: Address cardiovascular risk factors, bone health, and infection risk 3

5. Overlooking pregnancy planning: Switch from teratogenic medications (MMF, cyclophosphamide) to safer alternatives (azathioprine) when pregnancy is contemplated 1