Efficacy of tacrolimus versus cyclosporine after lung transplantation: an updated systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials

Background Little data supports using tacrolimus versus cyclosporin for immunosuppression concerning acute rejection and bronchiolitis obliterans syndrome/Chronic Lung Allograft Dysfunction CLAD complications following lung transplantation (LTx). Our goal was to evaluate the use of tacrolimus versus cyclosporine in preventing these complications after LTx. Methods We included randomized controlled trials (RCTs) by searching PubMed, Web of Science, SCOPUS, and Cochrane through January 10th, 2024. We pooled dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD) with a 95% confidence interval (CI). Results We included Four RCTs with a total of 677 patients. Tacrolimus was significantly associated with decreased risk of acute rejection (RR: 1.21, 95% CI [1.03, 1.42], I-2 = 25%, P = 0.02) compared with cyclosporine, bronchiolitis obliterans syndrome/CLAD (RR: 1.87, 95% CI [1.26, 2.77], I-2 = 52%, P = 0.002), and treatment withdrawal (RR: 3.11, 95% CI [2.06, 4.70], I-2 = 0%, P = < 0.00001). However, tacrolimus significantly increased the risk of new-onset diabetes (RR: 0.33, 95% CI [0.12, 0.91], I-2 = 0%, P = 0.03), and kidney dysfunction (RR: 0.79, 95% CI [0.66, 0.93], I-2 = 0%, P = 0.006). In contrast, there was no difference in the incidence of all-cause mortality (RR: 91, 95% CI [0.68, 1.22], I-2 = 0%, P = 0.53), arterial hypertension (RR: 2.40, 95% CI [0.41, 14.21], I-2 = 92%, P = 0.33), and new cancer (RR: 1.57, 95% CI [0.79, 3.10], I-2 = 4%, P = 0.20). Conclusion Tacrolimus has decreased acute rejection episodes and CLAD rate than cyclosporine, but it increased the risk of new-onset diabetes and kidney dysfunction.