Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis

Aim. To assess the relative efficacy and safety of low-dose cyclophosphamide (LCYC) and high-dose CYC (HCYC) as induction therapy for lupus nephritis. Methods. Bayesian random-effects network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of LCYC, HCYC, and mycophenolate mofetil (MMF) for induction therapy in patients with lupus nephritis. Results. Eleven RCTs (1212 patients) were included. MMF and LCYC showed similar overall response rates (OR 1.02, 95% credible interval [CrI] 0.51-2.02), and MMF showed a higher efficacy than HCYC (OR 1.48, 95% CrI 0.99-2.44). Similarly, LCYC showed a higher overall response than HCYC (OR 1.46, 95% CrI 0.83-2.86). Ranking probability based on SUCRA (surface under the cumulative ranking curve) indicated that MMF had the highest probability of being the best treatment for achieving an overall response (SUCRA=0.7461), followed by LCYC (SUCRA=0.6978) and HCYC (SUCRA=0.0561). LCYC showed the highest probability of decreasing the risk of serious infections (SUCRA=0.8513), followed by MMF (SUCRA=0.49387) and HCYC (SUCRA=0.1548). Conclusion. LCYC was an efficacious induction treatment for patients with lupus nephritis and had the highest probability of decreasing the risk of serious infections. Higher response rates and a more favorable safety profile suggest that LCYC is a good option for induction treatment in these patients.