Immunosuppressive therapy for kidney transplantation in children and adolescents: Systematic review and economic evaluation
Background: End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. Objectives: To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,® Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,® Sanofi) as induction therapy and immediate-release tacrolimus [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), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy’s Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,® Pfizer) and everolimus (Certican,® Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. Data sources: Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost). Review methods: Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. Results: Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC. Limitations: The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence. Conclusions: TAC is likely to be cost-effe tive (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
Citation
@article{m.2016,
author = {Haasova, M. and Snowsill, T. and Jones-Hughes, T. and
Crathorne, L. and Cooper, C. and Varley-Campbell, J. and
Mujica-Mota, R. and Coelho, H. and Huxley, N. and Lowe, J. and
Dudley, J. and Marks, S. and Hyde, C. and Bond, M. and Anderson, R.},
title = {Immunosuppressive Therapy for Kidney Transplantation in
Children and Adolescents: {Systematic} Review and Economic
Evaluation},
journal = {Health Technology Assessment},
volume = {20},
number = {61},
date = {2016-08-01},
url = {https://tristansnowsill.co.uk/immunosuppressive-therapy-for-kidney-transplantation-in-children.html},
doi = {10.3310/hta20610},
langid = {en},
abstract = {Background: End-stage renal disease is a long-term
irreversible decline in kidney function requiring kidney
transplantation, haemodialysis or peritoneal dialysis. The preferred
option is kidney transplantation followed by induction and
maintenance immunosuppressive therapy to reduce the risk of kidney
rejection and prolong graft survival. Objectives: To systematically
review and update the evidence for the clinical effectiveness and
cost-effectiveness of basiliximab (BAS) (Simulect,® Novartis
Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin
(Thymoglobuline,® Sanofi) as induction therapy and immediate-release
tacrolimus {[}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), generic MMF is manufactured by Accord Healthcare,
Actavis, Arrow Pharmaceuticals, Dr Reddy’s Laboratories, Mylan,
Sandoz and Wockhardt{]}, mycophenolate sodium, sirolimus (Rapamune,®
Pfizer) and everolimus (Certican,® Novartis Pharmaceuticals) as
maintenance therapy in children and adolescents undergoing renal
transplantation. Data sources: Clinical effectiveness searches were
conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via
Ovid), Cochrane Central Register of Controlled Trials (via Wiley
Online Library) and Web of Science {[}via Institute for Scientific
Information (ISI){]}, Cochrane Database of Systematic Reviews,
Database of Abstracts of Reviews of Effects and Health Technology
Assessment (HTA) (The Cochrane Library via Wiley Online Library) and
Health Management Information Consortium (via Ovid).
Cost-effectiveness searches were conducted to 15 January 2015 using
a costs or economic literature search filter in MEDLINE (via Ovid),
EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley
Online Library), Web of Science (via ISI), Health Economic
Evaluations Database (via Wiley Online Library) and EconLit (via
EBSCOhost). Review methods: Titles and abstracts were screened
according to predefined inclusion criteria, as were full texts of
identified studies. Included studies were extracted and quality
appraised. Data were meta-analysed when appropriate. A new discrete
time state transition economic model (semi-Markov) was developed;
graft function, and incidences of acute rejection and new-onset
diabetes mellitus were used to extrapolate graft survival.
Recipients were assumed to be in one of three health states:
functioning graft, graft loss or death. Results: Three randomised
controlled trials (RCTs) and four non-RCTs were included. The RCTs
only evaluated BAS and tacrolimus (TAC). No statistically
significant differences in key outcomes were found between BAS and
placebo/no induction. Statistically significantly higher graft
function (p \textless{} 0.01) and less biopsy-proven acute rejection
(odds ratio 0.29, 95\% confidence interval 0.15 to 0.57) was found
between TAC and ciclosporin (CSA). Only one cost-effectiveness study
was identified, which informed NICE guidance TA99. BAS {[}with TAC
and azathioprine (AZA){]} was predicted to be cost-effective at
£20,000-30,000 per quality-adjusted life year (QALY) versus no
induction (BAS was dominant). BAS (with CSA and MMF) was not
predicted to be cost-effective at £20,000-30,000 per QALY versus no
induction (BAS was dominated). TAC (with AZA) was predicted to be
cost-effective at £20,000-30,000 per QALY versus CSA (TAC was
dominant). A model based on adult evidence suggests that at a
cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC
are cost-effective in all considered combinations; MMF was also
cost-effective with CSA but not TAC. Limitations: The RCT evidence
is very limited; analyses comparing all interventions need to rely
on adult evidence. Conclusions: TAC is likely to be cost-effe tive
(vs. CSA, in combination with AZA) at £20,000-30,000 per QALY.
Analysis based on one RCT found BAS to be dominant, but analysis
based on another RCT found BAS to be dominated. BAS plus TAC and AZA
was predicted to be cost-effective at £20,000-30,000 per QALY when
all regimens were compared using extrapolated adult evidence.
High-quality primary effectiveness research is needed. The UK Renal
Registry could form the basis for a prospective primary study.}
}