PUK20 Cost-Utility Assessment of Sirolimus Versus Tacrolimus for Primary Prevention of Graft Rejection in Renal Transplant Recipients in Mexico (original) (raw)
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Transplantation Proceedings, 2011
Background. Renal replacement therapies which consist of renal transplantation and dialysis are the only treatment options for patients with terminal renal failure. These therapies have changed the outcome from being fatal to being a chronic disease. Kidney transplantation involves the use of immunosuppressive agents to prevent rejection. Currently, several immunosuppressive agents have shown efficacy, safety, and different costs. Objective. The aim was to evaluate the cost-effectiveness of early conversion from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or everolimus versus continuous treatment with tacrolimus among renal transplantat patients in Colombia. Methods. We performed systematic literature review to extract data for clinical effectiveness and safety of tacrolimus replacement schemes for immunosuppressive therapy in renal transplantation in adults. A Markov model in TreeAge was developed, simulating the patient's natural history with renal transplantation. The perspective of the Colombian Health System was used, including only direct costs. The cost-effectiveness ratio and incremental cost-effectiveness ratio were estimated. Deterministic and probabilistic sensitivity analyses were performed. A 5% discount rate was applied in costs and health results. Results. Results for the replacement of tacrolimus to sirolimus are provided. The cost per year of additional life gained for sirolimus was Col$2,441,171.43; the cost for avoided loss was Col$4,014,152.84. The acceptability curve shows that a strategy with sirolimus is the most cost-effective one. Conclusions. This study suggested that the sirolimus strategy is cost-effective in Colombia for patients with renal transplantation using as threshold less than three times the gross domestic product (GDP) per capita of Colombia per life of years gained.
Patient Preference and Adherence, 2014
Background: End-stage renal disease is the irreversible final stage of chronic kidney disease and is fatal when not managed by either transplantation or dialysis. Transplantation is generally preferred over dialysis. However, to prevent graft rejection or loss, lifelong immunosuppression is required. Tacrolimus is currently the cornerstone of post-transplantation immunosuppression. The study aim was to carry out an economic evaluation of immunosuppression, including more recent agents such as a once-daily prolonged-release formulation of tacrolimus (Advagraf™) and belatacept, relative to a twice-daily immediate-release formulation of tacrolimus (Prograf™). Methods: A model was constructed comprising six states: onset of biopsy-confirmed acute rejection, functioning graft with or without a biopsy-confirmed acute rejection, non-functioning graft (dialysis), re-transplantation, and death. Data on clinical effectiveness were derived from a systematic literature review and the model captured the effects of patient adherence to immunosuppressant therapy on graft survival using relative risk of graft survival and published data on adherence in patients using Advagraf and Prograf. In the base case, the time horizon was 25 years and one-way and probabilistic sensitivity analyses were conducted. Results: The analysis demonstrated that Prograf was cost-effective when compared with cyclosporin and belatacept and was more effective than sirolimus, but would not be considered cost-effective against sirolimus. The modeled improvement in the adherence profile of patients using Advagraf relative to Prograf resulted in both improved clinical outcomes and reduced costs. Conclusion: Prograf was more clinically effective than cyclosporin, belatacept, and sirolimus, supporting its current positioning as the mainstay of immunosuppressive therapy in renal transplant recipients. Based on improved patient adherence with Advagraf, the model projected that Advagraf would be both more effective and less costly than Prograf. Replacing Prograf with Advagraf as the standard of care for post-transplant immunosuppression could likely result in both cost savings and improved clinical outcomes.
Nephrology Dialysis Transplantation, 2004
Background. The new immunosuppressive drugs control acute rejection better, and have potentially short-term economic advantages. However, their long-term cost-effectiveness must still be determined. The Spanish study of chronic transplant nephropathy provides data that facilitates the assessment of the economic importance of maintenance immunosuppression (MI). Methods. We determined the frequency of use of the different MI drugs and their combinations in three renal transplantation cohorts performed in 1990, 1994 and 1998 (total: 3279), and their evolution over time. Based on the real costs found in a medium-sized service in our country at the end of 2000, the mean annual costs of MI drugs were calculated. We performed a multivariate analysis of graft survival in the 1998 cohort. Results. In 1990 and 1994, cyclosporine (CsA) with or without azathioprine (AZA) was used almost exclusively as the initial MI drug. In 1998, 76% received mycophenolate mofetil (MMF) and 20% tacrolimus (TAC). During their follow-up, a growing number of patients from the 1990 and 1994 groups were converted to MMF (12 and 17%) and TAC (4 and 8%), while the treatment of those from 1998 remained stable. Using prices from the year 2000, the mean cost of the MI at the end of the first year in 1998 (E5380) was almost double that of 1994 (E2902) and 1990 (E2855). In these two groups, the mean cost remained stable until 1996; afterwards, it increased in both, more rapidly in the 1994 (24.8%) than in the 1990 (17.3%) group, although it remained significantly inferior to that of 1998. Correction for the evolution of the drug prices and the peseta purchasing value lessened these changes in an important way. The new regimens allowed for the withdrawal of steroids in a greater proportion of cases; TAC was associated with a less frequent use of lipidlowering drugs and antihypertensive drugs. In the whole patient group, the regimens with MMF and/or TAC showed a tendency to greater mean life of the organs, but without reaching statistical significance in the multivariate analysis of patients in 1998. Conclusions. The introduction of new drugs in the MI applied in Spain has had an important economic impact since 1996. Their cost-effectiveness is still pending confirmation in our country.
2013
The aim of this study was to determine budget impact of conversion from cyclosporine (CsA) to sirolimus (SRL) in renal transplant therapy (RTT) from the perspective of insurance organizations in Iran. Methods: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF), and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively.
International Journal of Pharmacy and Pharmaceutical Sciences, 2020
Objective: To assess the utility of number needed to treat (NNT) as a tool for cost effectiveness analysis. Methods: Two monoclonal antibodies (MAbs), used for induction therapy viz basiliximab and daclizumab in renal transplantation, were identified. Pivotal placebo controlled clinical trials, mentioned in the innovator package inserts, were compared and analyzed for acute graft rejection and graft survival at 12 mo. NNT viz-a-vis cost was calculated and compared. Results: Daclizumab was comparable to basiliximab for acute graft rejection (NNT 10 vs. 9) but better for graft survival (20 vs. 25) at 12 mo, when used along with triple drug regimen (cyclosporine, azathioprine and corticosteroid). However, considering the cost of regimen for these drugs, in terms of NNT, basiliximab was more cost effective (INR 12,52,044 vs. 28,70,400 for acute rejection and INR 34,77,900 vs. 57,40,800 for graft survival). On the other hand, when these MAbs were used along with dual drug regimen (cyclosporine and corticosteroid), daclizumab was more cost effective for graft survival at 12 mo. The higher cost of daclizumab regimen (INR 2,87,040 vs. 1,39,116 for basiliximab) was offset by its substantially lower NNT (20 vs. 58-75 for one extra graft survival at 12 mo). Conclusion: This study demonstrates the utility of NNT in ascertaining relative effectiveness of treatment modalities that would help to formulate appropriate healthcare policies.
Drugs - Real World Outcomes, 2016
Background As of 2014, there were approximately 8300 patients with a functioning liver transplant in the UK Transplant Registry, with 880 liver transplants performed in 2013-2014 alone. Tacrolimus, typically used in combination with steroids and mycophenolate mofetil, currently represents the cornerstone of post-transplant immunosuppression in liver transplant recipients. Objectives The objective of the present study was to evaluate the cost-effectiveness of prolonged-release (PR) tacrolimus (Advagraf Ò , Astellas Pharma Inc., Tokyo, Japan) versus branded immediate-release (IR) tacrolimus (Prograf Ò , Astellas Pharma Inc., Tokyo, Japan) in liver transplant recipients in the UK. Methods A model was developed in Microsoft Excel to estimate costs associated with immunosuppressive medications and retransplantation. Three-year patient and graft survival data were taken from a recent retrospective registry analysis and dose data were taken from prescribing information. Costs in 2014 pounds sterling were taken from the British National Formulary and the National Health Service National Tariff. Results Over a 3-year time horizon, the numbers needed to treat with PR tacrolimus relative to IR tacrolimus were 14 to avoid one graft loss and 18 to avoid one death. The model was sensitive to dosing assumptions, with incremental cost estimates varying between a saving of £1642 (standard deviation £885) per patient, assuming the same per-kilogram dosing of PR tacrolimus (Advagraf Ò) and IR tacrolimus (Prograf Ò) and an increase of £1350 (£964) using RCT dose data. Conclusion Data from a recent analysis of routine clinical practice data in liver transplant recipients on PR tacrolimus and IR tacrolimus showed significant differences in longterm graft survival in favor of PR tacrolimus. Modeling these data in the UK showed that, over a 3-year time horizon, one graft would be saved for every 14 patients treated with PR tacrolimus with minimal impact on costs when compared with branded IR tacrolimus (Prograf Ò). Key Points Recent data from routine clinical practice shows that once-daily prolonged-release formulations of tacrolimus result in improved graft survival in liver transplant recipients relative to twice-daily immediate-release tacrolimus.
Transplantation proceedings, 1996
Source of effectiveness data The effectiveness data were derived from a review and synthesis of completed studies. Modelling A Markov decision-analytic model was used to compare the cost-effectiveness of the de novo use of Sim and Neoral formulations of cyclosporin A in cadaveric kidney transplant recipients. Outcomes assessed in the review The outcomes used as input parameters to the model were the probabilities of rejection, graft loss due to rejection, graft loss due to other courses, and death. These data were calculated for each of 6 cycles, where each cycle was of 15 days' duration to encompass a 3-month observation period. Study designs and other criteria for inclusion in the review The data were derived from 3 prospective, parallel group, randomised, double-blind, comparative trials of de novo Sim versus Neoral conducted during 1992 and 1993. Additional data were derived from a cohort study of patients selected from a US administrative database. The authors did not report the inclusion or exclusion criteria used to select the studies for inclusion in the review. In addition, they did not provide details of the sources of the data. Sources searched to identify primary studies Not reported. Criteria used to ensure the validity of primary studies Not reported. Methods used to judge relevance and validity, and for extracting data Not reported. Number of primary studies included Four primary data sources were included in the review. Methods of combining primary studies Not reported. Investigation of differences between primary studies The authors reported there were differences between the primary studies in terms of the participants and the organ rejection rates. The cohorts were adjusted to control for differences in the ethnic group. Other differences between the studies were not investigated or explained in terms of the study design or the outcomes. Results of the review The only results reported were the 3-month acute rejection rates. These were: for the Neoral (US) cohort, 32%; for the Neoral (European) cohort, 45%;
Transplantation Proceedings, 2016
Background. The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys. Methods. This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion. Patients were followed up for 1 year. Outcomes included reasons for conversion, acute rejection, patient and graft survival, graft status, and safety. Results. The intention-to-treat population included 52 patients (mean age, 48.7 years). Calcineurin inhibitor nephropathy (40%) and chronic allograft nephropathy (25%) were the most frequent reasons for conversion. Two acute rejections occurred during followup, but no patients experienced graft loss. One patient died during follow-up, and 3 patients died within 1 month of the last sirolimus dose. Levels of serum creatinine and creatinine clearance remained stable from baseline to week 52/53. Mean proteinuria measured in a subset of patients was 0.2 AE 0.2 g/24 hours before conversion and increased to 0.6 AE 1.2 g/24 hours at week 24/25 and 0.5 AE 0.6 g/24 hours at week 52/53. Adverse events were consistent with those in previous conversion trials; the most common were infections and infestations (54%). Conclusions. This pilot study illustrates the potential benefits of sirolimus in recipients of ECD kidneys in Argentina. Larger, randomized controlled trials are needed to confirm these findings and to clarify the long-term benefits of sirolimus in this patient population. This study was sponsored by Pfizer Inc.