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Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.

Ekberg, Henrik LU ; Bernasconi, Corrado; Nöldeke, Jana; Yussim, Alexander; Mjörnstedt, Lars; Erken, Ugur; Ketteler, Markus and Navrátil, Pavel (2010) In Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 25. p.2004-2010
Abstract
BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or... (More)
BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS: The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS: Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
volume
25
pages
2004 - 2010
publisher
Oxford University Press
external identifiers
  • wos:000280027400046
  • pmid:20106825
  • scopus:77952978213
ISSN
1460-2385
DOI
10.1093/ndt/gfp778
language
English
LU publication?
yes
id
3263d2f0-fc6a-43a3-bab5-4c8f770db88c (old id 1540517)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20106825?dopt=Abstract
date added to LUP
2010-02-03 10:55:59
date last changed
2017-02-12 04:20:49
@article{3263d2f0-fc6a-43a3-bab5-4c8f770db88c,
  abstract     = {BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS: The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS: Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.},
  author       = {Ekberg, Henrik and Bernasconi, Corrado and Nöldeke, Jana and Yussim, Alexander and Mjörnstedt, Lars and Erken, Ugur and Ketteler, Markus and Navrátil, Pavel},
  issn         = {1460-2385},
  language     = {eng},
  pages        = {2004--2010},
  publisher    = {Oxford University Press},
  series       = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
  title        = {Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.},
  url          = {http://dx.doi.org/10.1093/ndt/gfp778},
  volume       = {25},
  year         = {2010},
}