Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data

Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data

Author Knoll, Greg A. Google Scholar
Koko, Madzouka B. Google Scholar
Lick, Ranjeeta Ma Google Scholar
Beck, Andrew Google Scholar
Buenaventura, Chieny D. Google Scholar
Ducharme, Robin Google Scholar
Barsoum, Rashad Google Scholar
Bernasconi, Corrado Google Scholar
Blydt-Hansen, Tom D. Google Scholar
Ekberg, Henrik Google Scholar
Felipe, Claudia R. Autor UNIFESP Google Scholar
Firth, John Google Scholar
Gallon, Lorenzo Google Scholar
Gelens, Marielle Google Scholar
Glotz, Denis Google Scholar
Gossmann, Jan Google Scholar
Guba, Markus Google Scholar
Morsy, Ahmed Ali Google Scholar
Salgo, Rebekka Google Scholar
Scheuermann, Earnst H. Google Scholar
Tedesco-Silva, Helio Autor UNIFESP Google Scholar
Vitko, Stefan Google Scholar
Watson, Christopher Google Scholar
Fergusson, Dean A. Google Scholar
Institution Ottawa Hosp
Univ Ottawa
Cairo Univ
Limites Med Res
Univ Manitoba
Lund Univ
Universidade Federal de São Paulo (UNIFESP)
Addenbrookes Hosp
Northwestern Univ
Maastricht Univ
St Louis Hosp
Hosp JW Goethe
Univ Munich
Goethe Univ Frankfurt
Inst Klin Expt Med
Univ Cambridge
Abstract Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.Design Systematic review and meta-analysis of individual patient data.Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival.Results the search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. the most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls.Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. the benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.
Language English
Sponsor Pfizer
Date 2014-11-24
Published in Bmj-british Medical Journal. London: Bmj Publishing Group, v. 349, 14 p., 2014.
ISSN 1756-1833 (Sherpa/Romeo, impact factor)
Publisher Bmj Publishing Group
Extent 14
Origin http://dx.doi.org/10.1136/bmj.g6679
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000346115400003
URI http://repositorio.unifesp.br/handle/11600/38466

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