Comparison of the Efficacy and Safety of Leflunomide and Cyclophosphamide as Induction Treatment in Lupus Nephritis: Systematic Literature Review and Meta-Analysis

Introduction: Although new agents are frequently being used in developed countries for lupus nephritis(LN) treatment, they are hard to access in low resource settings. Leflunomide(LEF) may be an alternative agent in the treatment of LN especially for patients who are intolerant or refractory to cyclophospgamide(CYC) in these settings. Thus a systematic literature review was performed to analyze studies that compare LEF and CYC in LN. Method: Cochrane Reviews, MEDLINE, Ovid, Scopus, Web of Science were screened for the studies that compare LEF and CYC as induction regimen in LN. Meta-analyses for parameters of primary outcome (complete response) and secondary outcomes (partial response, total response - sum of complete response and partial response, change in albumin, creatininine, proteinuria, systemic lupus disease activity index-SLEDAI and adverse events) were performed. Results: Eleven studies in the meta-analysis by Cao and the randomized controlled trial of Zhang M were included. Meta-analyses demonstrated that LEF was superior to CYC in LN patients in achieving complete response, total response and in reducing proteinuria. Both drugs had similar efficacy in achieving partial remission, maintaining creatinine albumin levels and in reducing SLEDAI scores. Although a meta-analysis of adverse events was not possible, LEF was associated with less leukopenia and menstrual abnormalities but with more hypertension. Conclusion: LEF may be a potential alternative to CYC in the treatment of LN patients with its comparable efficacy and acceptable safety profile. Larger studies of longer duration in LN patients of different ethnicities is necessary before more robust conclusions can be reached.