Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients.Cochrane Database Syst Rev. 2013 May 31CD
Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without causing adverse effects.
To assess the benefits and harms of tacrolimus versus cyclosporin for primary immunosuppression in lung transplant recipients.
We searched the Cochrane Renal Group's Specialised Register to 10 April 2013 through contact with the Trials Search Co-ordinator using search terms relevant to this review. We also searched Science Citation Index Expanded and the Transplant Library to 20 April 2013.
We included all randomised controlled trials (RCT) that compared any dose and duration of administration of tacrolimus versus cyclosporin as primary immunosuppressive treatment in lung transplant recipients. Our selection criteria required that all included patients received the same additional immunosuppressive therapy within each study.
DATA COLLECTION AND ANALYSIS
Three authors extracted data. For dichotomous data we used risk ratio (RR) and used mean difference (MD) for continuous data, each with 95% confidence intervals (CI). Methodological components of the included studies were used to assess risk of systematic errors (bias). Trial sequential analysis was used to assess risk of random errors (play of chance).
We included three studies that enrolled a total of 413 adult patients that compared tacrolimus with microemulsion or oral solution cyclosporin. All studies were found to be at high risk of bias. Tacrolimus seemed to be significantly superior to cyclosporin regarding the incidence of bronchiolitis obliterans syndrome (RR 0.46, 95% CI 0.29 to 0.74), lymphocytic bronchitis score (MD -0.60, 95% CI -1.04 to -0.16), treatment withdrawal (RR 0.27, 95% CI 0.16 to 0.46), and arterial hypertension (RR 0.67, 95% CI 0.50 to 0.89). However, the finding for arterial hypertension was not confirmed when analysed using a random-effects model (RR 0.54, 95% CI 0.17 to 1.73). Furthermore, trial sequential analysis found that none of the meta-analyses reached the required information sizes and cumulative Z-curves did not cross trial sequential monitoring boundaries. Diabetes mellitus occurred more frequently among people in the tacrolimus group compared with the cyclosporin group when the fixed-effect model was applied (RR 4.24, 95% CI 1.58 to 11.40), but no difference was found when the random-effects model was used for analysis (RR 4.43, 95% CI 0.75 to 26.05). Again, trial sequential analysis found that the required information threshold was not reached and cumulative Z-curve did not cross the trial sequential monitoring boundary. No significant difference between treatment groups was observed regarding mortality (RR 1.06, 95% CI 0.75 to 1.49), incidence of acute rejection (RR 0.89, 95% CI 0.77 to 1.03), numbers of infections/100 patient-days (MD -0.15, 95% CI -0.30 to 0.00), cancer (RR 0.21, 95% CI 0.04 to 1.16), kidney dysfunction (RR 1.41, 95% CI 0.93 to 2.14), kidney failure (RR 1.57, 95% CI 0.28 to 8.94), neurotoxicity (RR 7.06, 95% CI 0.37 to 135.19), and hyperlipidaemia (RR 0.60, 95% CI 0.30 to 1.20). Trial sequential analysis showed the required information thresholds were not reached for any of these outcome measures.