Efficacy and safety of nine immunosuppressive agents for primary focal segmental glomerulosclerosis in adults: a pairwise and network meta-analysis

Immunosuppressants are widely used as the preferred treatment for primary focal segmental glomerulosclerosis (pFSGS). Nevertheless, controversies persist regarding the effectiveness and side effects of different immunosuppressive medications. From July 2023 until June 2024, we systematically searched PubMed, Cochrane Library, Web of Science, clinicalrials.gov, SinoMed, Chinese Biomedical, Chinese National Knowledge Infrastructure, Wanfang, and VIP information. Randomized controlled trials comparing different immunosuppressants were included in adult patients with pFSGS, with total remission (TR) and 24-h urine total protein (24-h UTP) as the main outcome measures. We identified 20 RCTs comparing nine different immunosuppressants for the final analysis. Most immunosuppressants showed better therapeutic effects in TR compared to non-immunosuppressive therapies (NIT), with risk ratios (RRs) of 2.22 (95% CI 1.41-3.50) for cyclosporin, 2.10 (1.57-2.80) for leflunomide-combined steroids, 2.01 (1.24-3.27) for chlorambucil-combined steroids, 1.98 (1.17-3.33) for tacrolimus-combined steroids, 1.89 (1.36-2.63) for cyclosporin-combined steroids, 1.67 (1.28-2.18) for mycophenolate mofetil-combined steroids, and 1.47 (1.21-1.80) for steroids. Only mycophenolate mofetil-combined steroids (SMD -11, 95% CI -21 to -0.64) showed significant superiority in reducing 24-h UTP when compared with NIT. The subgroup analyses of steroids-resistant nephrotic syndrome (SRNS) patients showed that CSA + STE was significantly superior than the NIT group, with RR of 10.5 (95% CI 2.28-44.35). Steroids remain the recommended initial treatment for pFSGS. For those patients with SRNS, CSA + STE might be the best choice for improving the rate of TR. LEF + STE and MMF + STE also appear to offer a steroid-saving alternative to high-dose glucocorticoids for patients.