Interleukin-2 Receptor Antagonist Induction Therapy in Lung Transplantation—A Meta-Analysis of Reconstructed Time-to-Event Data

TL;DR

This study evaluates the effectiveness of interleukin-2 receptor antagonist induction therapy in lung transplant patients, finding possible survival benefits but inconclusive results due to study limitations.

Contribution

A meta-analysis of reconstructed time-to-event data to assess IL2-AR induction therapy in lung transplantation.

Findings

IL2-AR induction showed improved overall survival compared to standard care, but results lost significance in sensitivity analyses.

No significant differences were found for acute rejection, BOS, hospital LOS, or time until extubation.

Study heterogeneity and design limitations leave the efficacy of IL2-AR therapy inconclusive.

Abstract

Objectives: Lung transplantation is a life-saving option for patients with end-stage lung diseases, yet immunosuppression management remains challenging. Induction therapy with interleukin-2 receptor antagonists (IL2-AR), such as basiliximab and daclizumab, is designed to reduce acute rejection and improve graft survival. However, its efficacy compared with alternative agents or no induction therapy remains uncertain. This study aimed to evaluate the impact of IL2-AR induction on clinical outcomes in lung transplant recipients. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies comparing IL2-AR induction with antithymocyte globulin (ATG), alemtuzumab, or no induction therapy were included. The primary outcomes were overall survival and freedom from acute rejection. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (BOS), hospital length of stay (LOS), and time until extubation. Kaplan–Meier curves were reconstructed for long-term outcomes. Random effects model was performed. Results: Twelve studies comprising 27,855 patients were included. IL2-AR induction was associated with improved overall survival compared to standard of care (HR 0.88; 95%CI 0.85–0.93; p < 0.01). However, sensitivity analyses, including two-stage meta-analysis and leave-one-out analysis, revealed a loss of statistical significance. No significant differences were found for freedom from acute rejection (p = 0.774) or secondary outcomes, including freedom from BOS (p = 0.455), hospital LOS (p = 0.423), and time until extubation (p = 0.186). Conclusions: IL2-AR therapy may be associated with improved survival after lung transplantation; however, evidence remains inconclusive due to heterogeneity and limitations in study design.

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