Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial

Clin Rheumatol. 2019 Mar;38(3):859-867. doi: 10.1007/s10067-018-4348-z. Epub 2018 Nov 13.

Abstract

Objectives: A prospective, multi-center, randomized controlled study was conducted to evaluate the efficacy and safety of a 24-week course low-dose leflunomide combined with prednisone in the induction treatment of proliferative lupus nephritis in Chinese patients.

Method: Patients (n = 100) with biopsy-proved proliferative lupus nephritis were enrolled in this study. They were randomized into two groups and received either leflunomide or cyclophosphamide in conjunction with prednisone for 24 weeks. Leflunomide was given orally with a loading dose of 40 mg/day for 3 days followed by 20 mg/day. Intravenous cyclophosphamide was administered monthly at a dosage of 0.8-1.0 g. The primary efficacy outcome was the frequency of complete remission and partial remission at week 24. The secondary outcomes included changes of urinary protein excretion, serum albumin, complement 3, anti-dsDNA antibody level, and systemic lupus erythematosus disease activity index (SLEDAI) after 24-week therapy.

Results: Of 100 patients, 48 received leflunomide combined with prednisone and other 52 received cyclophosphamide with concomitant prednisone. There were no statistically significant differences between groups in complete remission rate and partial remission rate. At week 24, 23% of patients in the leflunomide group and 27% of patients in the cyclophosphamide group achieved complete remission (P = 0.64), while 56% of patients in the leflunomide group and 42% of patients in the cyclophosphamide group achieved partial remission at week 24 (P = 0.16). SLEDAI, serum albumin, complement 3, anti-dsDNA antibody level, and urinary protein excretion improved significantly in both groups. No significant difference was seen in the changes of clinical parameters after therapy between the two groups. There was no significant difference in side effects in both groups.

Conclusions: Compared with cyclophosphamide, low-dose leflunomide in combination with prednisone showed both effectiveness and safety in the induction therapy of proliferative lupus nephritis in Chinese patients.

Keywords: Efficacy; Leflunomide; Lupus nephritis; Prospective study.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Antinuclear
  • China
  • Complement C3 / immunology
  • Cyclophosphamide / therapeutic use*
  • DNA / immunology
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Induction Chemotherapy
  • Leflunomide / therapeutic use*
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Proteinuria
  • Serum Albumin / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Antinuclear
  • Complement C3
  • Glucocorticoids
  • Immunosuppressive Agents
  • Serum Albumin
  • Cyclophosphamide
  • DNA
  • Leflunomide
  • Prednisone