The Effects of Calcineurin Inhibitor Avoidance on Renal Function and Graft Histology After Kidney Transplantation: A Prospective, Randomized Comparison of Tacrolimus and Sirolimus

Dean, Patrick G.; Larson, TS; Rea, David; Griffin, Meagan; Textor, Stephen C.; Schwab, T. R.; Gloor, James M.; Cosio, F.; Lund, William J.; Kremers, Walter K.; Nyberg, SL; Ishitani, M.; Barrio, María Isabel Prieto; Velosa, Jorge A.; Stegall, Mark D.

doi:10.1097/00007890-200407271-00241

Cited by 5 publications

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“…The estimated mean daily dosing at 1 year, separately reported for the first 59 people randomised to TAC, was 6.3 mg per day (SD 0.9 mg per day). 361 The model, however, applied costs to the TAC arm at a quoted BNF recommended dose of 0.25 mg/kg/day for a group of individuals of 70 kg mean weight, thus resulting in a mean daily dose of 17.5 mg, which is considerably higher than the actual drug use that corresponds to the efficacy outcomes used by the model. The dose behind the TAC drug acquisition costs used in the Novartis submission is also larger than the mean daily doses for immediate-release TAC reported by Tedesco-Silva et al, 349 which Astellas adopted in its submission, and which are consistent with the report of Dean et al…”

Section: Critical Appraisal Of Company Submissionsmentioning

confidence: 99%

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

Jones-Hughes

Snowsill

Haasova

et al. 2016

Health Technol Assess

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BackgroundEnd-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival.ObjectivesTo review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect®, Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin®, Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport®, Sandoz; Capexion®, Mylan; Modigraf®, Astellas Pharma; Perixis®, Accord Healthcare; Prograf®, Astellas Pharma; Tacni®, Teva; Vivadex®, Dexcel Pharma), prolonged-release tacrolimus (Advagraf®Astellas Pharma), belatacept (BEL) (Nulojix®, Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip®, Zentiva; CellCept®, Roche Products; Myfenax®, Teva), mycophenolate sodium (MPS) (Myfortic®, Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune®, Pfizer) and everolimus (EVL) (Certican®, Novartis) as maintenance therapy in adult renal transplantation.MethodsClinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association’s electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time–state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.ResultsEighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY.LimitationsFor included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled.Future workHigh-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome.ConclusionOnly a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000–30,000 per QALY.Study registrationThis study is registered as PROSPERO CRD42014013189.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Critical Appraisal Of Company Submissionsmentioning

confidence: 99%

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

Jones-Hughes

Snowsill

Haasova

et al. 2016

Health Technol Assess

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Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Webster

Lee

Chapman

et al. 2006

Cochrane Database of Systematic Reviews

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TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed.

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Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Hahn

Hodson

Hamiwka

et al. 2019

Cochrane Database of Systematic Reviews

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The Effects of Calcineurin Inhibitor Avoidance on Renal Function and Graft Histology After Kidney Transplantation: A Prospective, Randomized Comparison of Tacrolimus and Sirolimus

Cited by 5 publications

References 0 publications

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

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