Single Bolus Antithymocyte Globulin Versus Basiliximab Induction in Kidney Transplantation With Cyclosporine Triple Immunosuppression: Efficacy and Safety

Kyllönen, L.; Eklund, B; Pesonen, Eero; Salmela, K.

doi:10.1097/01.tp.0000268084.64888.f3

Cited by 70 publications

(75 citation statements)

References 21 publications

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“…However, despite multiple reports demonstrating reasonable safety and possible medical advantages to SD‐rATG induction in renal transplantation, there remains a concern in the transplant community as to the early safety of this approach 9, 10, 13, 18, 19. The present multicenter study was designed to rigorously address these remaining safety concerns using a primary composite end point based on either the physiologic consequences of a severe rATG reaction (fever, hypotension, hypoxia) or the possible severe sequelae (cardiac events and DGF) 20, 21, 22, 23, 24.…”

Section: Discussionmentioning

confidence: 99%

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

Stevens

Wrenshall

Miles

et al. 2016

American Journal of Transplantation

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A previous nonblinded, randomized, single‐center renal transplantation trial of single‐dose rabbit anti‐thymocyte globulin induction (SD‐rATG) showed improved efficacy compared with conventional divided‐dose (DD‐rATG) administration. The present multicenter, double‐blind/double‐dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD‐rATG versus DD‐rATG induction for noninferiority in early (7‐day) safety and tolerability. Ninety‐five patients (randomized 1:1) received 6 mg/kg SD‐rATG or 1.5 mg/kg/dose DD‐rATG, with tacrolimus‐mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12‐month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD‐rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD‐rATG induction to be noninferior to DD‐rATG induction in early tolerability and equivalent in 12‐month safety. (Clinical Trials.gov #NCT00906204.)

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Section: Discussionmentioning

confidence: 99%

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

Stevens

Wrenshall

Miles

et al. 2016

American Journal of Transplantation

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“…[100][101][102][103] The pooled results at 1 year with five studies 98,[100][101][102][103] suggest less BPAR in BAS than PBO or no induction (OR = 0.53; favours BAS; 95% CI 0.40 to 0.70, I 2 = 0.0%, τ 2 = 0.0). Furthermore, Sheashaa et al 99 reported BPAR at 10 years, at which time BAS continues to show a beneficial effect compared with no induction (OR = 0.41, 95% CI 0.18 to 0.96).…”

Section: Adult Randomised Controlled Trial Evidencementioning

confidence: 99%

“…[100][101][102][103] Six studies reported results at 1-year follow-up. [98][99][100][101][102][103] The pooled results at 1 year with five studies 98,[100][101][102][103] suggest no difference between BAS and PBO or no induction: OR = 0.82 (favours BAS; 95% CI 0.56 to 1.21, I 2 = 0.0%, τ 2 = 0.0); 98,[100][101][102][103] one study reported zero events in both arms. 99 …”

Section: Adult Randomised Controlled Trial Evidencementioning

confidence: 99%

“…In the adult evidence identified by the parallel HTA, three studies comparing BAS and no induction [97][98][99] and four studies comparing BAS with PBO reported AR. [100][101][102][103] The pooled results at 1 year with five studies 98,[100][101][102][103] suggest less BPAR in BAS than PBO or no induction (OR = 0.53; favours BAS; 95% CI 0.40 to 0.70, I 2 = 0.0%, τ 2 = 0.0).…”

Section: Adult Randomised Controlled Trial Evidencementioning

confidence: 99%

“…In the adult evidence identified by the parallel HTA, three RCTs comparing BAS and no induction reported mortality [97][98][99] and four studies compared BAS with PBO. [100][101][102][103] Six studies reported results at 1-year follow-up.…”

Section: Adult Randomised Controlled Trial Evidencementioning

confidence: 99%

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Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

Haasova

Snowsill

Jones-Hughes

et al. 2016

Health Technol Assess

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BackgroundEnd-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.ObjectivesTo 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 sourcesClinical 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 methodsTitles 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.ResultsThree 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.LimitationsThe RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.ConclusionsTAC is likely to be cost-effective (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.Study registrationThis study is registered as PROSPERO CRD42014013544.FundingThe National Institute for Health Research HTA programme.

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Interleukin 2 receptor antagonists for kidney transplant recipients

Webster

Ruster

McGee

et al. 2010

Cochrane Database of Systematic Reviews

144

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Given a 38% risk of rejection, per 100 recipients compared with no treatment, nine recipients would need treatment with IL2Ra to prevent one recipient having rejection, 42 to prevent one graft loss, and 38 to prevent one having CMV disease over the first year post-transplantation. Compared with ATG treatment, ATG may prevent some experiencing acute rejection, but 16 recipients would need IL2Ra to prevent one having CMV, but 58 would need IL2Ra to prevent one having malignancy. There are no apparent differences between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects.

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Single Bolus Antithymocyte Globulin Versus Basiliximab Induction in Kidney Transplantation With Cyclosporine Triple Immunosuppression: Efficacy and Safety

Abstract: ATG induction significantly reduced DGF. Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival. The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion.

Cited by 70 publications

References 21 publications

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

Interleukin 2 receptor antagonists for kidney transplant recipients

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