What is the typical multitarget therapy approach for lupus nephritis?

Multitarget Therapy in Lupus Nephritis

The recommended multitarget therapy for lupus nephritis combines mycophenolic acid (MPA) at a target dose of 1-2 g/day with a calcineurin inhibitor (particularly tacrolimus), along with glucocorticoids, as this approach has shown excellent efficacy, especially in patients with nephrotic-range proteinuria. 1

Initial Treatment Options for Lupus Nephritis

Class III or IV (±V) Lupus Nephritis

• First-line options include:
  • Mycophenolic acid (MPA) (target dose: 2-3 g/day) with glucocorticoids 1
  • Low-dose intravenous cyclophosphamide (500 mg every 2 weeks for 6 doses) with glucocorticoids 1
  • Multitarget therapy: MPA (1-2 g/day) plus a calcineurin inhibitor (especially tacrolimus) with glucocorticoids - particularly effective for nephrotic-range proteinuria 1

Class V Lupus Nephritis

• MPA (target dose: 2-3 g/day) with glucocorticoids is recommended as initial treatment due to best efficacy/toxicity ratio 1
• Alternative options include:
  • Intravenous cyclophosphamide 1
  • Calcineurin inhibitors (especially tacrolimus) in monotherapy or combined with MPA - particularly for nephrotic-range proteinuria 1

Glucocorticoid Regimen

• Intravenous pulses of methylprednisolone (total dose 500-2500 mg, depending on disease severity) 1
• Followed by oral prednisone (0.3-0.5 mg/kg/day) for up to 4 weeks 1
• Tapered to ≤7.5 mg/day by 3-6 months 1

Maintenance Therapy

• For patients who responded to initial treatment, maintenance therapy includes:

  • MPA at lower doses (target dose: 1-2 g/day) or azathioprine (2 mg/kg/day) 1
  • Combined with low-dose prednisone (2.5-5 mg/day) 1
  • Continued for at least 3-5 years 1, 2

• For multitarget maintenance therapy specifically:

  • Tacrolimus (2-3 mg/day) 3
  • MPA (0.5-0.75 g/day) 3
  • Prednisone (10 mg/day) 3
  • This regimen has shown a low renal relapse rate and fewer adverse events compared to azathioprine maintenance 3

Adjunctive Treatments

• Hydroxychloroquine should be co-administered (dose not exceeding 5 mg/kg/day, adjusted for GFR) 1, 2
• Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for patients with proteinuria (UPCR >500 mg/g) or hypertension 1
• Statins for persistent dyslipidemia (target LDL-cholesterol <100 mg/dl) 1

Monitoring and Treatment Goals

• Treatment aims for:

  • Preservation or improvement of kidney function 1
  • Reduction in proteinuria of at least 25% by 3 months 1
  • Reduction in proteinuria of at least 50% by 6 months 1
  • UPCR target below 500-700 mg/g by 12 months (complete clinical response) 1

• Regular monitoring should include:

  • Body weight, blood pressure, serum creatinine, eGFR 1
  • Serum albumin, proteinuria, urinary sediment 1
  • Serum C3 and C4, anti-dsDNA antibody levels 1
  • Complete blood cell count 1

Management of Refractory Disease

• For non-responding/refractory disease:
  • Switch from MPA to cyclophosphamide or vice versa 1, 2
  • Consider rituximab (1000 mg on days 0 and 14) 1
  • Consider calcineurin inhibitors (especially for class V nephritis) 1, 2

Clinical Considerations and Caveats

• Patients with nephrotic-range proteinuria at baseline may require an additional 6-12 months to reach complete clinical response 1
• Patients at high risk for kidney failure (reduced GFR, crescents, fibrinoid necrosis, severe interstitial inflammation) may benefit from high-dose intravenous cyclophosphamide (0.5-0.75 g/m² monthly for 6 months) 1
• Multitarget therapy has shown fewer adverse events compared to traditional regimens, making it particularly valuable for long-term management 3
• Gradual withdrawal of treatment (glucocorticoids first, then immunosuppressive drugs) can be attempted after at least 3-5 years of therapy in complete clinical response 1