Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant
Date
2019Journal
JAMA network openPublisher
JAMA Network OpenType
Article
Metadata
Show full item recordAbstract
Importance: Median 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. Objectives: To 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 Participants: This 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. Exposures: Cell 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 Measures: Survival was the primary outcome; chronic rejection incidence and subsequent mortality were secondary outcomes. Results: Among 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 Relevance: Sirolimus 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.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071611799&doi=10.1001%2fjamanetworkopen.2019.10297&partnerID=40&md5=08f90f65b62238796e4273be9a83d1f4; http://hdl.handle.net/10713/10834ae974a485f413a2113503eed53cd6c53
10.1001/jamanetworkopen.2019.10297
Scopus Count
Collections
Related articles
- Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.
- Authors: Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS
- Issue date: 2005 May
- Long-term kidney allograft function and survival in prednisone-free regimens: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.
- Authors: Chhabra D, Skaro AI, Leventhal JR, Dalal P, Shah G, Wang E, Gallon L
- Issue date: 2012 Mar
- Calcineurin inhibitor-free immunosuppression in pediatric renal transplantation: a viable option?
- Authors: Höcker B, Tönshoff B
- Issue date: 2011 Feb 1
- Belatacept for kidney transplant recipients.
- Authors: Masson P, Henderson L, Chapman JR, Craig JC, Webster AC
- Issue date: 2014 Nov 24
- Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial.
- Authors: Zuckermann A, Reichenspurner H, Birsan T, Treede H, Deviatko E, Reichart B, Klepetko W
- Issue date: 2003 Apr