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

  • 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.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Author:Greg A. Knoll, Madzouka B. Kokolo, Ranjeeta Mallick, Andrew Beck, Chieny D. Buenaventura, Robin Ducharme, Rashad Barsoum, Corrado Bernasconi, Tom D. Blydt-Hansen, Henrik Ekberg, Claudia R. Felipe, John Firth, Lorenzo Gallon, Marielle Gelens, Denis Glotz, Jan Gossmann, Markus Guba, Ahmed Ali Morsy, Rebekka Salgo, Earnst H. Scheuermann, Helio Tedesco-Silva, Stefan Vitko, Christopher Watson, Dean A. Fergusson
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25422259
Parent Title (English):The BMJ
Publisher:BMJ Publ. Group
Place of publication:[S.l.]
Document Type:Article
Year of Completion:2014
Date of first Publication:2014/11/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/11/29
Page Number:13
Copyright © Knoll et al 2014. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0