A Randomized, Prospective, Pharmacoeconomic Trial of Tacrolimus versus Cyclosporine in Combination with Thymoglobulin in Renal Transplant Recipients

Hardinger, Karen L.; Bohl, Daniel L.; Schnitzler, Mark A.; Lockwood, Mark B.; Storch, Gregory A.; Brennan, Daniel C.

doi:10.1097/01.tp.0000162980.68628.5a

Cited by 67 publications

(74 citation statements)

References 14 publications

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“…The remaining trials (one induction study 97 and 20 maintenance studies 75,81,85,91,[99][100][101][102]104,109,110,112,114,115,117,[119][120][121][122]127 ) did not report any information about blinding participants to treatment allocation.…”

Section: Treatment Allocation Masked From Participantsmentioning

confidence: 99%

“…Again, four maintenance studies 58,77,143,150 were rated as 'partial' for clinician blinding because blinding occurred for only a limited time, and one induction study 95 was rated as 'unclear' because, although it was a PBO-controlled trial, no further details were reported about blinding. The other 20 maintenance studies 75,81,85,91,[99][100][101][102]104,109,110,112,114,115,117,[119][120][121][122]127 did not report any details about clinician blinding.…”

Section: Treatment Allocation Masked From Cliniciansmentioning

confidence: 99%

“…The majority of trials (52 maintenance studies, 51,[75][76][77][79][80][81][82][83][84]86,89,[91][92][93][94][99][100][101][102][104][105][106]108,109,[111][112][113][114][116][117][118][119][120][121][122]130,131,133,138,140,141,[144][145][146][147][148][149][151][152][153]155 nine induction studies, [71][72][73]…”

Section: Treatment Allocation Masked From Outcome Assessorsmentioning

confidence: 99%

“…Fifty-four trials 51,[72][73][74][76][77][78][79][81][82][83][84][85][87][88][89][91][92][93]95,96,[98][99][100][102][103][104][105][106][108][109][110][111][112][113][115][116][117][118][119][120]124,127,131,134,135,139,141,[143][144][145][153][154][155] did not report any information on allocation concealment, whereas 20 trials 71,…”

Section: Concealment Of Allocationmentioning

confidence: 99%

“…Fifty-seven trials (48 maintenance studies, 51,58,77,[80][81][82]84,86,94,99,100,102,[104][105][106][107][108][109][113][114][115][116][117][119][120][121][124][125][126][127]131,132,134,138,139,[141][142][143][144][145][146][147]149,150,152,154,156,157 eight induction studies 71,72,74,87,97,128,137 and one study …”

Section: Baseline Characteristicsmentioning

confidence: 99%

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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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