Project description:ImportanceMedian survival after lung transplant is less than 6 years. Standard maintenance therapy typically includes tacrolimus and an antimetabolite (mycophenolate mofetil or azathioprine). Replacing the antimetabolite with sirolimus after postoperative wound healing may improve long-term survival due to antifibrotic, antiproliferative, and antiaging effects of sirolimus.ObjectivesTo compare survival between patients receiving sirolimus?plus?tacrolimus vs mycophenolate mofetil plus tacrolimus (the most common maintenance therapy) and to identify the combination of induction and maintenance therapy associated with the highest survival.Design, setting, and participantsThis cohort study of US recipients of lung transplants from January 1, 2003, through August 31, 2016, analyzed United Network for Organ Sharing (UNOS) data from January 1 through September 13, 2018. Because initiation of sirolimus therapy is usually delayed 3 to 12 months after lung transplant, primary analyses were based on patients alive and free of chronic rejection and malignant disease at 1 year in all groups, whereas sensitivity analyses used appropriate methods to include all patients from transplant time. Regression models adjusted for available potential confounders, including transplant center performance.ExposuresCell cycle inhibitor maintenance therapies, including sirolimus (n?=?219), mycophenolate mofetil (n?=?5782), mycophenolate sodium (n?=?408), azathioprine (n?=?2556), and concurrent sirolimus plus mycophenolate mofetil (n?=?54), were compared within a tacrolimus-based regimen. Combinations of each induction (basiliximab, daclizumab, antithymocyte globulin, alemtuzumab, or none) and maintenance (tacrolimus plus sirolimus, mycophenolate mofetil, or azathioprine) therapy were also compared.Main outcomes and measuresSurvival was the primary outcome; chronic rejection incidence and subsequent mortality were secondary outcomes.ResultsAmong this population of 9019 patients (median age, 57 years [interquartile range {IQR}, 46-63 years]; 5194 men [57.6%]), sirolimus?plus?tacrolimus was associated with better survival than mycophenolate mofetil plus tacrolimus (median, 8.9 years [IQR, 4.4-12.7 years] vs 7.1 years [IQR, 3.6-12.1 years]; adjusted hazard ratio [aHR],?0.71; 95% CI, 0.56-0.89; P?=?.003). Chronic rejection incidence (aHR,?0.75; 95% CI, 0.61-0.92) and mortality after chronic rejection (aHR,?0.52; 95% CI, 0.31-0.81) were lower with sirolimus?plus?tacrolimus. Compared with mycophenolate mofetil plus tacrolimus, survival differences for sirolimus plus mycophenolate mofetil plus tacrolimus (aHR,?1.14; 95% CI, 0.79-1.65), mycophenolate sodium plus tacrolimus (aHR,?0.95; 95% CI, 0.77-1.17), and azathioprine?plus?tacrolimus (aHR,?0.93; 95% CI, 0.84-1.02) were not significant. The induction-maintenance combination with the highest survival was sirolimus?plus?tacrolimus without induction therapy (median survival, 10.7 years [IQR, 7.3-12.7 years]; aHR,?0.48; 95% CI, 0.31-0.76; P?=?.002) compared with mycophenolate mofetil plus tacrolimus with induction therapy (median survival, 7.4 years [IQR, 3.9-12.6 years]).Conclusions and relevanceSirolimus?plus?tacrolimus was associated with improved patient survival after lung transplant compared with mycophenolate mofetil plus tacrolimus; no antibody induction therapy with sirolimus?plus?tacrolimus was associated with maximal survival.
| S-EPMC6716294 | biostudies-literature
