A Cost-effectiveness Analysis of Rabbit Antithymocyte Globulin Versus Antithymocyte Globulin-fresenius as Induction Therapy for Patients With Kidney Transplantation From Donation After Cardiac Death in China.

PURPOSE: Induction immunosuppression therapy is used to support optimal outcomes in kidney transplantation. This study was to assess the cost-effectiveness of rabbit antithymocyte globulin (r-ATG) versus ATG-Fresenius (ATG-F) in kidney transplantation in the Chinese setting from the perspective of the health care payer. METHODS: A 2-part survival model was developed, consisting of a short-term part and a long-term part. The short-term part analyzed the first year, using the decision tree, and consisted of the functioning transplant, acute rejection (AR), delayed graft function (DGF), dialysis, and death health states. The long-term part analyzed 2 to 5 years, using Markov model, and consisted of the functioning transplant, chronic dysfunction, recurring primary disease, dialysis, and death health states, with capture of the association between DGF and graft loss. Costs, including drug acquisition and other direct medical costs, were derived from China IQVIA database (formerly known as IMS) hospitaldatabase, chart review, and physician interviews. Clinical outcomes and utility were retrieved from published literature. The model calculated quality-adjusted life-years (QALYs) and total costs per patient. Costs and QALYs were discounted at an annual rate of 3.5%. Univariate sensitivity analysis and probability sensitivity analysis (PSA) were conducted to assess the impact of uncertainty of the variables on the results. FINDINGS: Patients who received r-ATG had more clinical effectiveness than patients who received ATG-F mainly because of less AR, DGF, and dialysis. The incremental QALY was 0.01 over a 1-year time horizon and 0.0496 over a 5-year time horizon. R-ATG and ATG-F drug costs were ¥10,783 and ¥8409, respectively. However, the total treatment costs of the r-ATG arm were lower than the ATG-F arm because of lower costs related to DGF, AR, dialysis, and adverse events. In total, r-ATG saved ¥5423 over the 1-year and ¥7042 over the 5-year time horizon. R-ATG was dominant with lower total direct medical costs and higher QALYs compared with ATG-F. Both univariate sensitivity analysis and PSA found the robustness of the model results. PSA results indicated that r-ATG was cost-effective compared with ATG-F in 86.81% of the simulations, considering <3 times the gross domestic product per capita as the threshold. IMPLICATIONS: From the perspective of the health care payer, r-ATG should be considered as the preferred treatment agent for induction therapy for Chinese patients undergoing kidney transplantation because of its lower overall medical costs and greater QALYs gained compared with ATG-F. The study was limited by lack of long-term efficacy data among the Chinese population and lack of comprehensive real-world higher quality costs data.

Induction therapy with rabbit antithymocyte globulin versus basiliximab after kidney transplantation: a health economic analysis from a German perspective.

A health economic analysis was undertaken based on the 1-year database from a randomized study of rabbit anti-human thymocyte immunoglobulin (rATG) versus basiliximab, in kidney transplantation using resource utilization data and cost estimates from three German hospitals. A three-state Markov model was applied to estimate cost-effectiveness to 10 years post-transplant. Total mean treatment cost per patient to year 1 post-transplant was €62 075 vs. €59 767 for rATG versus basiliximab (P < 0.01). rATG therapy was associated with similar treatment costs to basiliximab by year 2, and a predicted cumulative treatment cost saving of €4 259 under rATG versus basiliximab by year 10 post-transplant. The mean number of quality-adjusted life years (QALYs) per patient by year 1 was 0.809 vs. 0.802 in the rATG and basiliximab cohorts, respectively (P = 0.38), with cumulative QALYs of 6.161 and 6.065 per patient by year 10. By year 2, the cumulative cost per QALY was slightly lower under rATG (€35 378) than basiliximab (€35 885), progressing to a saving of €1 041 under rATG for the cumulative cost per QALY by year 10. In conclusion, this model indicates that rATG induction provides a modest increase in QALYs with lower long-term costs than basiliximab in deceased-donor high-risk kidney transplant patients.

Cost-Effectiveness of Antibody-Based Induction Therapy in Deceased Donor Kidney Transplantation in the United States.

BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER - cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits.

PREventing Delayed Graft Function by Driving Immunosuppressive InduCtion Treatment (PREDICT-DGF): study protocol for a randomized controlled trial.

BACKGROUND: In kidney transplantation, the use of Anti-Thymocyte Globulins (ATG) as induction therapy has been described as a possible treatment for reducing the prevalence of Delayed Graft Function (DGF). ATG possesses pharmaceutical proprieties that could help control the lesions caused by ischemia reperfusion injury. However, other studies have questioned this potential protective effect. We hypothesized that the benefits related to ATG for reducing DGF prevalence may be higher and more consistently recognized if only patients with high DGF risk are considered. We recently proposed a scoring system entitled DGFS (Delayed Graft Function Score) for such stratification of kidney transplant recipients according to their risk of DGF. Using the DGFS calculation, we aim to determine whether a short course of ATG can decrease the incidence of DGF in comparison with Basiliximab in kidney transplant recipients with low immunological risk but high DGF risk. METHODS: We conduct a phase IV, open label, randomized, multicentric and prospective study, to compare ATG in parallel with a control group treated by Basiliximab. The 1:1 randomized allocation of patients between groups is stratified on the clinical center, and on the hypothermic machine-perfusion device. We aimed to include a total of 384 patients to achieve a statistical power at 0.80. The study was initiated at the Nantes University hospital in July 2014, with data collection continuing until April 2018, and publication of the results proposed for 2019. DISCUSSION: The main expected benefits of this study are i) the reduction of unjustified ATG over-prescriptions associated with serious adverse events, ii) the reduction of chance losses related to ATG under-prescription, iii) the decrease in the incidence of DGF which was described as a risk factor of graft failure and patient death, and iv) the reduction in hospitalization duration and number of post transplantation dialysis sessions, both being associated with reduced medical costs. In conclusion, the current study is innovative by proposing a more efficient and personalized induction therapy. TRIAL REGISTRATION: The study was registered in the Clinical Trials Registry (# NCT02056938, February 5, 2014), and in the European Clinical Trials Database (EudraCT #2014-000332-42, January 30, 2014).

Polyclonal versus monoclonal induction therapy in a calcineurin inhibitor-free immunosuppressive therapy in renal transplantation: a comparison of efficacy and costs.

BACKGROUND: Induction therapy in renal transplantation reduces the incidence of acute rejection (AR) in expanded criteria donation (ECD) and donation after cardiac death (DCD). We compared the efficacy of Thymoglobulin (Sanofi-Aventis, Spain), ATG Fresenius (ATG-Fresenius, Spain), and Simulect (Novartis Farm, Spain) in a calcineurin-free protocol in ECD and DCD renal transplantation by evaluating patient survival, graft survival, and AR at 1 year and overall costs. METHODS: An observational retrospective study was performed using our database of 289 consecutive cadaveric ECD renal transplant recipients (n = 178) and DCD recipients (n = 111) from April 1999 to December 2011. Induction therapy consisted of Simulect, Thymoglobulin, and ATG Fresenius. Calcineurin-inhibitor (CNI)-free maintenance therapy consisted of mycophenolate mofetil or sodium and steroids. RESULTS: There were no differences in the patients' demographic characteristics or patient and graft survival. One-year AR rates were equivalent (ECD: 10%, 19.1%, 17.7% versus DCD: 14.3%, 7.1%, 16.7%). Leukopenia and thrombopenia were significantly more frequent in the ECD group treated with polyclonal induction. The average total cost of transplantation was higher in the ECD group but there were no significant differences in the average total cost between ECD and DCD: 39,970.31 ± 7,732€ versus 35,058.34 ± 6,801€ (P = NS). CONCLUSION: Our study shows the same efficacy with polyclonal and monoclonal antibody induction and a CNI-free treatment regimen in ECD and DCD renal transplantation with no differences in overall costs at 1 year after transplantation.

Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study.

UNLABELLED: Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00548405.

Low-dose rabbit anti-thymoglobin globulin versus basiliximab for induction therapy in kidney transplantation.

We conducted a single-center prospective double-arm open-labeled study on kidney transplant patients from 2010 to 2011 to evaluate the efficacy of induction therapy using low, single-dose rabbit-antithymocyte globulin (r-ATG), 1.5 mg/kg on Day 0 (n = 80, 60 males, mean age 35.9 years), versus basiliximab (Interleukin-2 blocker) 20 mg on Days 0 and 4 (n = 20, 12 males, mean age 45.1 years) on renal allograft function in terms of serum creatinine (SCr), rejection and infection episodes and patient/graft survival and cost. Demographic and post-transplant follow-up including immunosuppression was similar in both groups. In the r-ATG group, donors were unrelated (spouse, n = 25), deceased (n = 31) and parents/siblings (others), with a mean HLA match of 1.58. Donors in the basiliximab group were living unrelated (spouse, n = 15) and deceased (n = 5), with a mean HLA match of 1.56. No patient/graft was lost in the r-ATG group over a mean of one year follow-up, and the mean SCr was 1.28 mg/dL with 7.5% acute rejection (AR) episodes; infections were also not observed. In the basiliximab group, over the same period of follow-up, there was 95% death-censored graft survival, and the mean SCr was 1.23 mg/dL with 10% AR episodes. One patient died due to bacterial pneumonia and one succumbed to coronary artery disease; one graft was lost due to uncontrolled acute humoral and cellular rejection. The cost of r-ATG and basiliximab were $600 and $2500, respectively. We conclude that induction immunosuppressive therapy with a low-dose r-ATG may be a better option as compared with basiliximab in terms of graft function, survival and cost benefit in kidney transplant patients.

A review on comparing two commonly used rabbit anti-thymocyte globulins as induction therapy in solid organ transplantation.

INTRODUCTION: Two rabbit anti-thymocyte globulins (ATGs) (Thymoglobulin™ and ATG-Fresenius (ATG-F)™) have been used commonly for induction immunosuppression and treatment of acute rejection in solid organ transplantation. Therefore, literature review on comparative efficacy and side-effect profile of them would be of clinical interest. AREAS COVERED: This review evaluated all comparative studies in English language, focusing on the solid organ transplant patients who received Thymoglobulin or ATG-F as induction therapy. This review concluded that compared to ATG-F, Thymoglobulin possibly provides better protection against acute rejection and improves patient and graft survival but may result in more cytomegalovirus infection and post-transplant malignancy. Thymoglobulin produced more leukocyte depletion with a greater delay to recover, while ATG-F had more reduction effects on platelet and erythrocyte counts with an increased need to erythropoiesis-stimulating agent. EXPERT OPINION: The benefits of induction therapy with ATGs must be weighed against the costs and post-transplant complications. It is suggest that there is no substantial clinical difference between these two rabbit ATGs and each may be considered as induction therapy for solid organ transplantation based on availability and drug cost. Of special importance is adding antiviral therapy to the treatment regimen of patients who receive ATGs as induction therapy.

Clinical and economic analysis of delayed administration of antithymocyte globulin for induction therapy in kidney transplantation.

CONTEXT: The increasing number of marginal deceased kidney donors and an aging recipient population, prolonged hospitalization, and increased costs have destabilized the economic viability of kidney transplants. OBJECTIVE: To determine if a delay in the administration of the day-of-discharge dose of rabbit antithymocyte globulin would result in equivalent clinical outcomes with cost savings. DESIGN: Single-center, prospective, observational before-and-after study of adult kidney transplant recipients who received induction with rabbit antithymocyte globulin.Intervention-Patients who received a transplant between June 2006 and February 2009 and received rabbit antithymocyte globulin served as the control group. Patients who received a transplant between March 2009 and August 2010 and received rabbit antithymocyte globulin had the day-of-discharge dose delayed to the following day and administered in the clinic. A total of 231 patients (146 in the control group, 85 in the study group) were included. Baseline demographic and clinical characteristics were similar in the 2 groups. RESULTS: Patients who had delayed administration of rabbit antithymocyte globulin had shorter stays (3.9 vs 3.1 days, P< .001) and reduced inpatient costs for rabbit antithymocyte globulin (mean $860/patient); these changes were achieved without affecting acute rejection rates (5% vs 5%, P> .99) or readmission rates. In conclusion, delayed inpatient administration of rabbit antithymocyte globulin provided identical clinical outcomes while helping to reduce inpatient costs and increase timely discharges.

Modelling cost effectiveness of horse antithymocyte globulin for treating severe aplastic anaemia in Germany.

Acquired severe aplastic anaemia (AA) is a serious condition caused by immune-triggered bone marrow failure. For patients not eligible for bone marrow transplantation, treatment of choice is immunosuppression by a combined treatment with antithymocyte globulin (ATG) and cyclosporine. The debate on treatment optimization in AA is focused on conflicting data regarding ATG preparations from horse (h-ATG) versus rabbit (r-ATG), recently favouring h-ATG. H-ATG has been withdrawn from the European market in 2007. Reimbursement for imported preparations from outside Europe is frequently denied in negotiations with statutory health insurance companies. This raises the question of whether h-ATG is cost effective and a sensible investment with regard to healthcare budgets as well as patient health. We modelled the cost effectiveness of r-ATG versus h-ATG based on a recent randomized trial and cost data provided by the hospital pharmacy of Jena University Hospital. We calculated the amount of life years gained and the average incremental costs per life year gained when comparing h-ATG and r-ATG. Our calculations revealed average incremental costs per life year gained of 11,033.80 for the examined patient population treated with h-ATG when compared to r-ATG. Assuming a cost effectiveness threshold of 25,000-35,000 per life year gained, our calculations demonstrate cost effectiveness of h-ATG as compared to r-ATG.

Efficacy and safety of extended-duration inpatient-to-outpatient rabbit antithymocyte globulin induction in de novo kidney transplant recipients: 6-month outcomes.

BACKGROUND: In an effort to reduce length of stay (LOS) in kidney transplant recipients otherwise ready for discharge, we developed a protocol to extend rabbit antithymocyte globulin (rATG) induction therapy into the outpatient setting through peripheral dose administration. METHODS: A retrospective review of outpatient rATG group (n=185) that received the first two rATG doses inpatient and subsequent doses outpatient was used, compared with concurrently transplanted patients who received all doses of rATG as an inpatient (n=99). RESULTS: The outpatient group received more rATG (cumulative mg/kg induction) than the inpatient-only group (median [range], 4.8 mg/kg [3.2-10.0] vs. 4.4 mg/kg [2.8-8.6]; P<0.01). Outpatient usage avoided 246 hospital days that would have been required had rATG been administered in the inpatient setting. The incidences of perioperative leukopenia and thrombocytopenia were lower in the outpatient rATG group versus inpatient-only group (5% vs. 21%, P<0.01, and 2% vs. 9%, P<0.01, respectively) but were similar by 3 months. The outpatient rATG group experienced shorter hospitalization LOS compared with the inpatient-only group (median LOS [range], 4 [2-11] vs. 5 [3-20] days; P<0.01) and lower 30-day readmission rates (30% vs. 42%, P=0.03). At 6 months, there were no differences in incidences of biopsy-proven rejection episodes. CONCLUSIONS: When implemented selectively among less complicated kidney transplant recipients, delayed extension of rATG into the outpatient setting was associated with LOS reduction and attendant cost saving without either increasing readmission rate or compromising short-term safety and efficacy.

Clinical and economic analysis of short-course versus standard-course antithymocyte globulin (rabbit) induction therapy in deceased-donor renal transplant recipients.

PURPOSE: The immunosuppressive effects of and costs associated with short-course antithymocyte globulin rabbit (ATG [rabbit]) therapy versus standard-course ATG (rabbit) therapy in deceased-donor renal transplant recipients were evaluated. METHODS: The records of 84 consecutive patients who received a deceased-donor renal transplant at the Montefiore Einstein Center for Transplantation in 2008 were retrospectively reviewed. Donor and recipient characteristics, including rates of biopsy-confirmed acute rejection, serum creatinine (SCr) levels, and frequency of complications, and drug costs were collected. Patients were excluded if they had donor-specific antibodies identified before transplantation or hepatitis-C-positive serology or were under 18 years of age. RESULTS: A total of 60 patients were included in the study, with 28 receiving short-course ATG (rabbit) therapy and 32 receiving standard-course ATG (rabbit) therapy. Baseline patient demographic characteristics were similar between groups. Six months after transplantation, biopsy-confirmed acute rejection episodes did not significantly differ between the short-course ATG (rabbit) and standard-course ATG (rabbit) groups (17.8% versus 12.5%, respectively), nor did SCr concentrations (1.56 mg/dL versus 1.85 mg/dL). The frequency of therapy-related leukopenia was greater in patients receiving standard-course ATG (rabbit). Patients treated with short-course ATG (rabbit) received a total mean dose of 4.6 mg/kg, compared with 7.3 mg/kg for patients in the standard-course ATG (rabbit) group, resulting in a mean cost saving of $2548 per patient. CONCLUSION: After six months, there were no significant differences in biopsy- confirmed acute rejection episodes or SCr levels between deceased-donor renal transplant recipients receiving short-course versus standard-course ATG (rabbit) induction therapy. The mean cost saving associated with short-course therapy was $2548 per patient.

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. MEASUREMENTS AND MAIN RESULTS: Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). CONCLUSION: Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Treatment for children with severe aplastic anemia and sickle cell disease in low income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO): Part III.

Treatment of hematologic disorders in low-income countries (LIC) is difficult. This report summarizes treatment of sickle cell disease and aplastic anemia by pediatric hematologists from 15 LIC who participate in the Monza International School of Pediatric Hematology/Oncology (MISPHO). Patients with severe sickle cell disease were treated with low dose hydroxyurea, which safely reduced vaso-occlusive crises. Patients with severe aplastic anemia fared poorly due to lack of availability and high cost of anti-thymocyte globulin and cyclosporine and lack of access to stem cell transplantation. Appropriate therapy was most likely to occur in MISPHO centers with an active twinning program with a center in a high-income country.

A randomized, prospective, pharmacoeconomic trial of tacrolimus versus cyclosporine in combination with thymoglobulin in renal transplant recipients.

BACKGROUND: To date, the clinical trials of tacrolimus (TAC) versus cyclosporine modified (CsA), have not defined which agent is more cost-effective for immunosuppression in renal transplant recipients especially in a quadruple immunosuppressive regimen. METHODS: The objective of this randomized, prospective study was to compare the clinical and economic outcomes of TAC versus CsA, in a regimen that consisted of Thymoglobulin induction, an antimetabolite, and prednisone. Between December 2000 and October 2002, 200 patients were enrolled and randomized in a 2:1 fashion (TAC n=134, CsA n=66). RESULTS: At 1 year, acute rejection (4% TAC vs. 6% CsA), patient survival (TAC 99% vs. CsA 100%), and graft survival (95% TAC versus 100% CsA, P=0.059) were similar. Serum creatinine levels were lower in the TAC group compared with the CsA group (1.3+/-0.3 vs. 1.6+/-0.7 mg/dL, P=0.03). The incidence of CMV infection was similar between the groups and two patients, both in the TAC arm, developed malignancy. Anti-hypertensive requirement (32% TAC vs. 32% CsA) and the incidence of posttransplant diabetes mellitus (4% TAC vs. 2% CsA) were similar. Pretransplant, fewer TAC patients received dyslipidemia treatment (40% TAC vs. 67% CsA, P=0.0005), while more CsA patients were able to discontinue these medications posttransplant (absolute change 25% TAC vs. 47% CsA). Total 12-month medication costs were similar (17,723 +/- 11,647 dollars TAC vs. 16,515 +/- 10,189 dollars CsA). CONCLUSIONS: When combined with Thymoglobulin induction, an antimetabolite, and corticosteroids, TAC and CsA are comparable in safety, efficacy, and cost in renal transplantation.

Comparison of induction based on continuous vs discontinuous administration of antithymocyte globulins in renal transplant patients: efficacy and long-term safety.

UNLABELLED: This retrospective study sought to compare two modes of administration of antithymocyte globulin (RATG) after renal transplantation. METHODS: Before 1993, group I patients (n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until serum creatinine level became <150 micromol/L. After 1993, group II patients (n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and thereafter the doses were adjusted to target a CD2 T-cell count <50/mm3. Both groups received steroids, azathioprine, and cyclosporine. The mean follow-up after transplantation was 117 +/- 31 months in group I and 93 +/- 19 months in group II. RESULTS: The RATG cumulative dose and consequently cost were significantly higher among group I than group II patients. Long-term patient and graft survival were similar in both groups. The rate of acute graft-rejection episodes was significantly higher among group I than group II patients. At 7 years posttransplantation, the serum creatinine level and creatinine clearance were similar in the two groups. The rate of cytomegalovirus infection, as well as the cumulative incidence of severe infections and cancers were also similar in both groups. Among the cancers, skin neoplasms represented 30% in group I and 26% in group II (P = ns). CONCLUSION: Adjusting RATG doses according to the CD2 lymphocyte count is safe, and a less expensive than using full doses.

Cyclosporine minimization and cost reduction in renal transplant recipients receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.

BACKGROUND: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels. METHODS: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter. RESULTS: Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P<0.001). CONCLUSION: With a quadruple immunosuppressive regimen and lower C2 targets than recommended for triple therapy, safe and effective cyclosporine minimization was achieved. Lower cyclosporine doses were achieved in C2-monitored patients compared with C0-monitored patients, translating into lower immunosuppressive costs.

Induction immunosuppression in kidney transplant recipients older than 60 years of age : safety and efficacy of ATGAM, OKT3 and Simulect.

BACKGROUND: The choice of induction immunosuppression for kidney transplantation in elderly recipients is dictated by the consideration of the risk of infection as well as efficacy in the prevention of acute rejection, thus allowing a reduction in subsequent maintenance immunosuppression and its attendant long-term adverse effects. OBJECTIVE: To compare the efficacy and safety of the antibody induction immunosuppression strategies in elderly recipients of kidney transplants. PATIENTS AND METHODS: We present retrospective data analysis on 183 kidney transplant recipients > or = 60 years of age at Hahnemann University Hospital (Philadelphia, PA, USA) over a 12-year period. We compared four consecutive cohorts of kidney transplant recipients receiving lymphocyte immune globulin, equine antithymocyte globulin (ATGAM) [n = 29]; muromonab CD3 (OKT3) [n = 45]; basiliximab (Simulect) with corticosteroid maintenance [n = 40]; and Simulect without corticosteroid maintenance (n = 69). RESULTS: Delayed graft function (DGF) was observed in 48% of patients receiving ATGAM, 35.6% in the OKT3 group and 35% in the Simulect group with corticosteroid maintenance and 36.2% in the Simulect group without corticosteroid maintenance. The rejection rate within the first 3 months was 31% in the ATGAM and OKT3 groups, 17.5% in the Simulect group with corticosteroid maintenance and 14.5% in the Simulect group without corticosteroid maintenance. These differences for DGF and acute rejection were statistically significant between patients receiving ATGAM and OKT3, ATGAM or OKT3 and both groups of Simulect (all p < 0.05). Patients receiving Simulect were free of adverse effects typically encountered by patients receiving polyclonal and monoclonal antibodies for induction. Patients receiving Simulect had much shorter hospital stays and benefited from significant reduction of costs compared with other groups. CONCLUSION: Our data indicate that kidney transplant recipients > or = 60 years of age benefit from induction therapy with Simulect followed by corticosteroid-free maintenance immunosuppression.

Cost-minimization study comparing Simulect vs. Thymoglobulin in renal transplant induction.

PURPOSE: Based on the data of clinical trial CHI-F-02 comparing the efficacy and safety of basiliximab (Simulect) vs. anti-thymocyte globulin (Thymoglobulin) in renal transplant induction, we carried out an economic evaluation. METHOD: This pharmacoeconomic study was a cost-minimization study, i.e. given the equivalent efficacy of the products, the strategy that minimized the cost of care was considered better. The cost of care was analyzed from the hospital perspective. MATERIAL: This 'piggyback' study of 100 patients estimated the direct medical costs incurred over 6 months of use of two strategies for renal transplant induction therapy. Direct medical costs are those of utilized medical resources: medications, hospital stays, dialysis, and physician visits and investigations not scheduled in the protocol. RESULTS: In the Simulect arm, significant reductions were found in the initial hospital stay duration and number of infectious episodes. Therefore, although the average cost of treatment was slightly higher with Simulect) than with Thymoglobulin (2964 vs. 2298 Euros), the cost of the initial hospitalization was significantly lower in the Simulect arm (10 907 vs. 11 967 Euros; p = 0.02). Furthermore the mean cost of infectious episodes was significantly lower in the Simulect arm (1056 vs. 1790 Euros, p = 0.03). Cytomegalovirus infection accounted for a significantly smaller proportion of this cost in the Simulect arm than in the Thymoglobulin arm (30% vs. 53%, p = 0.001). CONCLUSION: This study showed direct medical cost savings of 1159 Euros per patient in the Simulect arm, which more than compensated for the higher price of this immunosuppressive drug.