Background/Purpose: Cyclophosphamide (CYC) regimens improved renal outcomes, and have long been considered the gold standard for inducing renal remission and preventing renal flares in proliferative glomerulonephritis (WHO class III and IV). However, their benefits are outweighed by the significant drug-related adverse effects, such as an increased risk of serious infections and ovarian toxicity. Thus, other immunosuppressive drugs have been used for induction treatment of lupus nephritis, such as mycophenolate mofetil (MMF), and tacrolimus. However, evidence from a small number randomized controlled trials (RCT) comparing the relative efficacy and safety of tacrolimus or MMF with CYC, as induction agents in lupus nephritis, has been inconclusive, mainly because of their small sample sizes. This study aimed to assess the relative efficacy and safety of tacrolimus, MMF, and CYC as induction therapy for lupus nephritis.

Methods: RCTs examining the efficacy and safety of tacrolimus, MMF, and CYC for induction therapy in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs.

Results: Nine RCTs including 972 patients met the inclusion criteria. There pairwise comparisons were performed, including 11 direct comparisons. Tacrolimus showed a significantly higher overall response rate (complete remission plus partial remission) than CYC (OR 2.35, 95% credible interval (CrI) 1.03–5.45), and was more efficacious than MMF (OR 1.60, 95% CrI 0.70–3.57). MMF was superior to CYC in terms of overall response (OR 1.45, 95% CrI 0.96–2.42). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tacrolimus had the highest probability of being the best treatment for achieving the overall response (SUCRA = 0.9321), followed by MMF (SUCRA = 0.5385), and CYC (SUCRA = 0.0294). In terms of safety, tacrolimus showed the highest probability of decreasing the risk of serious infections (SUCRA = 0.9253), followed by MMF (SUCRA = 0.4027), and CYC (SUCRA = 0.1720).

Conclusion: Tacrolimus was the most efficacious induction treatment for patients with lupus nephritis, and had the highest probability of decreasing the risk of serious infections. Higher remission rates combined with a more favorable safety profile suggest that MMF is superior to CYC as induction treatment in these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-efficacy-and-safety-of-tacrolimus-mycophenolate-mofetil-and-cyclophosphamide-as-induction-therapy-for-lupus-nephritis-a-bayesian-network-meta-analysis-of-randomized-controlled-trials/