Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study
Condition: Systemic Lupus Erythematosus; Lupus Nephritis
MeSH terms: Nephritis; Lupus Nephritis; Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      Intravenous cyclophosphamide is considered to be the standard of care for treatment of
      proliferative lupus nephritis. However, its use is limited by potentially severe toxic
      effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative
      to cyclophosphamide. In a randomized, multicenter, open-label, controlled trial the
      investigators sought to compare the efficacy of oral cyclosporine A with intravenous pulse
      cyclophosphamide to induce durable remission in patients with lupus nephritis III-IV.
    

Detailed description: 
      Lupus nephritis occurs in 30-40% of adults with systemic lupus erythematosus and is
      associated with increased morbidity and mortality. Focal and diffuse proliferative forms of
      lupus nephritis are known to progress to chronic renal failure unless treated by
      immunosuppressive drugs. Cyclophosphamide and glucocorticoids are considered to be the
      standard of care for patients with proliferative lupus nephritis. However, cyclophosphamide
      may cause a number of toxic effects, such as bone marrow suppression, premature gonadal
      failure, hemorrhagic cystitis, opportunistic infections, and malignant disease. Hence,
      efforts are being made to find alternative therapeutic approaches. Cyclosporine is a potent
      immunosuppressive agent with a more selective mode of action through its unique effect on T
      cell mediated responses, and is widely used to treat a spectrum of autoimmune and glomerular
      diseases. Several retrospective series and one randomized trial provided evidence that
      Cyclosporine A could represent an efficient and safe therapy for proliferative lupus
      nephritis. In a randomized, multicenter, open-label, controlled trial we compared the
      efficacy of oral cyclosporine A with intravenous pulse cyclophosphamide to induce durable
      remission in patients with proliferative lupus nephritis.
    

Intervention name(s): Cyclosporine A; Cyclophosphamide
Intervention type(s): Drug; Drug
Intervention description(s): Cyclosporine arm (CyA group) consisted of oral cyclosporine A (CyA) 4-5mg/kg/day (given in two divided doses) for 9 months followed by gradually decreasing dose of cyclosporine (3.75-1.25 mg/kg/day) within the next 9 months. The dosage of concomitant glucocorticoids was driven and tapered according to a single treatment protocol.; Cyclophosphamide (CPH) therapeutic arm (CPH group) consisted of 8 boluses of intravenous cyclophosphamide (10mg/kg) given within 9 months in subsequently prolonged intervals (2x3weeks, 4x4 weeks, 2x6 weeks) followed by 4-5 oral cyclophosphamide boluses (10mg/d in 6-8 week intervals). The dosage of concomitant glucocorticoids was driven and tapered according to a single treatment protocol.
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: SLE; lupus nephritis; cyclosporine A; cyclophosphamide; active proliferative lupus nephritis (class III or IV according to WHO)