Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data
Top Cited Papers
Open Access
- 24 November 2014
- Vol. 349 (nov24 1), g6679
- https://doi.org/10.1136/bmj.g6679
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.Keywords
This publication has 51 references indexed in Scilit:
- Histological progression of chronic renal allograft injury comparing sirolimus and mycophenolate mofetil–based protocols. A single‐center, prospective, randomized, controlled studyPediatric Transplantation, 2010
- Renal Function, Efficacy, and Safety of Sirolimus and Mycophenolate Mofetil After Short-Term Calcineurin Inhibitor-Based Quadruple Therapy in De Novo Renal Transplant Patients: One-Year Analysis of a Randomized Multicenter TrialTransplantation, 2010
- Thymoglobulin Induction and Sirolimus Versus Tacrolimus in Kidney Transplant Recipients Receiving Mycophenolate Mofetil and SteroidsTransplantation, 2010
- Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical TrialAmerican Journal of Transplantation, 2010
- Subsequent Squamous- and Basal-Cell Carcinomas in Kidney-Transplant Recipients After the First Skin Cancer: Cumulative Incidence and Risk FactorsTransplantation, 2010
- First and subsequent nonmelanoma skin cancers: incidence and predictors in a population of New Zealand renal transplant recipientsNephrology Dialysis Transplantation, 2009
- Conversion From Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients: 24-Month Efficacy and Safety Results From the CONVERT TrialTransplantation, 2009
- Mammalian Target of Rapamycin Inhibitor Dyslipidemia in Kidney Transplant RecipientsAmerican Journal of Transplantation, 2008
- mToR inhibitors-induced proteinuria: mechanisms, significance, and managementTransplantation Reviews, 2008
- Comparison of Mortality in All Patients on Dialysis, Patients on Dialysis Awaiting Transplantation, and Recipients of a First Cadaveric TransplantNew England Journal of Medicine, 1999