Priority 8 from the Kidney Transplant PSP

UNCERTAINTY: What is the best combination of immunosuppressive drugs following kidney transplantation (e.g. azatiohprine or mycophenolate, belatacept, generic or proprietary (brand-name) drugs)?
Overall ranking Priority questions agreed on but not put in ranked order
JLA question ID 0037/8
Explanatory note Not available for this PSP

Existing Systematic Reviews: Knoll, G. A., Kokolo, M. B., Mallick, R., Beck, A., Buenaventura, C. D., Ducharme, R., Barsoum, R., Bernasconi, C., Blydt-Hansen, T. D., Ekberg, H., et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ. 2014;349:g6679
PMID: 25422259
Morgan, R. D., O'Callaghan, J. M., Knight, S. R., Morris, P. J.. Alemtuzumab Induction Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis. Transplantation. 2012;93(12):1179-1188 PMID: 22660659 ~
Webster, AC., Ruster, LP., McGee, R, Matheson, SL., Higgins, GY., Willis, NS., Chapman, JR., Craig, JC. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database of Systematic Reviews. 2010;(1):CD003897  PMID: 20091551 ~
Knight, S. R., Russell, N. K., Barcena, L., Morris, P. J. Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review. Transplantation. 2009;87(6):785-94 PMID: 19300178 ~
Webster AC, Taylor RRS, Chapman JR and Craig JC. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients.  Cochrane Database of Systematic Reviews 2005. CD003961 ~
Knight, S R., Morris, P J.  Steroid avoidance or withdrawal after renal transplantation increases the risk of acute rejection but decreases cardiovascular risk. A meta-analysis. Transplantation. 2010;89(1):1-14
PMID: 20061913
Masson, P., Henderson, L., Chapman, J. R., Craig, J. C., Webster, A. C. Belatacept for kidney transplant recipients. Cochrane Database of Systematic Reviews. 2014;11:CD010699  PMID: 25416857 ~
Goring, S. M., Levy, A. R., Ghement, I., Kalsekar, A., Eyawo, O., L'Italien, G. J., Kasiske, B. L. A network meta-analysis of the efficacy of belatacept, cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients. Current Medical Research & Opinion. 2014;30(8):1473-87  PMID: 24628478

Health Research Classification System category Renal and Urogenital
Extra information provided by this PSP
Original uncertainty examples

Could azathioprine replace MMF in immunosuppressive protocols after transplantation, remembering the large cost savings that would follow if successful? What new drugs are on the market ? What, if any, research is being done to find new and less toxic anti rejection meds for transplant patients What is the best way of preventing rejection in the recipient? what is the best combination of immunosuppressants for long-term kidney health? what is the best combination of immunosuppressants for long-term patient health? What is the next future of the immunosuppression therapy? What evidence is there that particular immunusuppressive drugs are better than others? Should not outcomes other than acute rejection rates be the endpoint for assessment? Will anti rejection treatment be improved Which medicines are the most effective in post-transplant patients? What is the best long term immunosuppressive drug regime in kidney transplantation? Can there be direct comparisons between proprietary and generic immunosuppressant

Comparison Drug
Submitted by Patients x 4 Clinicians x 10
Outcomes to be measured Patient and graft survival, graft function, adverse events
PSP information
PSP unique ID 0037
PSP name Kidney Transplant
Total number of uncertainties identified by this PSP. 90  (To see a full list of all uncertainties identified, please see the detailed spreadsheet held on the JLA website)
Date of priority setting workshop 3 February 2016