Maintenance Immunosuppression in Adult Lung Transplant Recipients: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract Background Lung transplantation is a definitive therapeutic option for selected patients with advanced pulmonary diseases. However, long-term outcomes remain suboptimal, largely driven by immunologically mediated complications, including acute rejection and chronic lung allograft dysfunction, as well as the cumulative toxicity of lifelong immunosuppression. Methods This study was conducted as a systematic review and meta-analysis in accordance with PRISMA recommendations. A comprehensive search of PubMed, Embase, and the Cochrane Library was performed from inception. Randomized controlled trials evaluating maintenance immunosuppressive regimens in adult lung transplant recipients were included. When appropriate, treatment effects were pooled using random-effects models and are reported as risk ratios (RR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I² statistic. Indirect comparisons were explored using a common comparator approach. Statistical analyses were performed using R software. Results Twelve randomized trials were included. Rates of graft loss and all-cause mortality were broadly similar across maintenance immunosuppressive regimens. Tacrolimus-based strategies were associated with lower rates of biopsy-proven acute rejection in selected comparisons. No consistent differences were observed for chronic lung allograft dysfunction, likely reflecting limited follow-up duration. Regimens incorporating mTOR inhibitors were associated with higher rates of treatment discontinuation. Overall, findings were influenced by variability across studies and limited statistical power for several outcomes. Conclusion Current randomized evidence does not support the superiority of any maintenance immunosuppressive regimen after lung transplantation. Rather than indicating therapeutic equivalence, these findings highlight persistent gaps in robust evidence, particularly for chronic lung allograft dysfunction, and underscore the need for adequately powered trials with longer follow-up to inform optimal post-transplant management.