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Two-Year Outcomes in Thoracic Transplant Recipients After Conversion to Everolimus With Reduced Calcineurin Inhibitor Within a Multicenter, Open-Label, Randomized Trial.

Gullestad, Lars; Mortensen, Svend-Aage; Eiskjær, Hans; Riise, Gerdt C; Mared, Lena LU ; Bjørtuft, Oystein; Ekmehag, Björn LU ; Jansson, Kjell; Simonsen, Svein and Gude, Einar, et al. (2010) In Transplantation 90(12). p.1581-1589
Abstract
BACKGROUND.: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS.: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS.: Of 245 patients who completed the month 12 visit, 235... (More)
BACKGROUND.: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS.: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS.: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS.: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable. (Less)
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keywords
Tacrolimus, Cyclosporine A, CNI, Everolimus, Certican, Renal impairment
in
Transplantation
volume
90
issue
12
pages
1581 - 1589
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000285377100052
  • pmid:21030905
  • scopus:78650832714
ISSN
1534-6080
DOI
10.1097/TP.0b013e3181fd01b7
language
English
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yes
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843bf617-50ed-458a-a613-60bc385272ca (old id 1710597)
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http://www.ncbi.nlm.nih.gov/pubmed/21030905?dopt=Abstract
date added to LUP
2010-11-05 13:48:46
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2018-07-15 03:40:42
@article{843bf617-50ed-458a-a613-60bc385272ca,
  abstract     = {BACKGROUND.: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS.: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS.: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P&lt;0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS.: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.},
  author       = {Gullestad, Lars and Mortensen, Svend-Aage and Eiskjær, Hans and Riise, Gerdt C and Mared, Lena and Bjørtuft, Oystein and Ekmehag, Björn and Jansson, Kjell and Simonsen, Svein and Gude, Einar and Rundqvist, Bengt and Fagertun, Hans E and Solbu, Dag and Iversen, Martin},
  issn         = {1534-6080},
  keyword      = {Tacrolimus,Cyclosporine A,CNI,Everolimus,Certican,Renal impairment},
  language     = {eng},
  number       = {12},
  pages        = {1581--1589},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Transplantation},
  title        = {Two-Year Outcomes in Thoracic Transplant Recipients After Conversion to Everolimus With Reduced Calcineurin Inhibitor Within a Multicenter, Open-Label, Randomized Trial.},
  url          = {http://dx.doi.org/10.1097/TP.0b013e3181fd01b7},
  volume       = {90},
  year         = {2010},
}