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Lilliu H, Brun-Strang C, Le Pen C, Büchler M, Al Najjar A, Priol G, Reigneau O, Lebranchu Y. Cost-minimization study comparing Simulect® vs. Thymoglobulin® in renal transplant induction. Clin Transplant 2004: 18: 247–253. © Blackwell Munksgaard, 2004 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. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The rabbit antithymocyte globulin Thymoglobulin first became available over 25 yr ago and is the most widely used lymphocyte-depleting preparation in solid organ transplantation. Thymoglobulin targets a wide range of T-cell surface antigens as well as natural killer-cell antigens, B-cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors, resulting in profound, long-lasting T-cell depletion. Randomized studies have established the anti-rejection efficacy of Thymoglobulin in kidney transplantation. Experimental and clinical data suggest that Thymoglobulin administration may ameliorate ischemia reperfusion injury, thus reducing the incidence of delayed graft function (DGF). Studies have demonstrated the benefit of using Thymoglobulin to facilitate immunosuppression minimization, both for corticosteroid and calcineurin inhibitor (CNI) withdrawal or avoidance, with potential improvement in cardiovascular and renal outcomes. The optimal cumulative dose for Thymoglobulin induction is 6-7.5 mg/kg, with vigilant short- and long-term monitoring of hematological status. Induction with Thymoglobulin is now indicated in immunologically high-risk patients, in those at increased risk of DGF and to maintain efficacy in low-risk transplant recipients receiving steroid or CNI minimization or avoidance regimens. We suggest that in future trials Thymoglobulin be tested with costimulation signal blockers and other immunosuppressants with the objective of establishing operational tolerance., (© 2012 John Wiley & Sons A/S.)

Background: In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant., Methods: All patients completing the one-yr core study on-treatment were eligible to enter the extension study., Results: Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events., Conclusion: These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function.

Background: Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate., Methods: A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability., Results: At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group., Conclusion: Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.

The number of older patients living with a functioning kidney graft is increasing. However the safety of the immunosuppressive treatment and quality of life in this population have not yet been determined. All patients grafted in France since 1969, born before the January 1 1926 and living with a functioning graft on January 1 2000 were included in this national study including all 34 French transplant centers. Renal function, immunosuppressive treatment, comorbid conditions and quality of life were assessed. From the initial population of 446 patients, 113 (26.2%) were still alive in 2000 (study population). Mean age was 76 yr (range: 74-80) with a mean post-transplant follow-up of 9.9 yr (0.1-28.7). Average serum creatinine level was 129 micromol/L (55-286). Immunosuppression was heterogeneous and included triple therapy (18.6%), dual therapy (41.6%) and monotherapy (40.8%). A history of cancer was noted in 36 of the 113 patients (32.1%) whereas hypertension was the most frequent co-morbid condition (80.3%). Estimated quality of life using the Karnofsky scale was between 80 and 100 in 78.4% of the patients. The immunosuppressive regimen in older renal transplant recipients living with a functioning graft varied widely among the 34 French transplant centers. Renal function in this group of patients was good and quality of life seemed excellent. Cardiovascular disease and malignancies were the main co-morbid conditions.

Background: Two hundred and forty cadaveric renal transplant recipients given anti-thymocyte globulin (Thymoglobulin) as induction immunotherapy were followed up prospectively to review safety and efficacy., Methods: The median number of infusions was 10 [2-21] with a cumulative dose of 8.8 mg/kg [2.0-23.2 mg/kg]. During the fortnight following transplantation, 231 patients (96%) received a calcineurin inhibitor; all patients were given steroids and azathioprine or mycophenolate mofetil. At 1 yr, 60% of patients were on tripletherapy, 38% on bitherapy, and 2% on monotherapy; 20% had discontinued steroids., Results: Tolerance was excellent with no cases of anaphylaxis. The commonest adverse event was fever (55%). Eighteen patients developed serum sickness on median day 11 [10-14]. Seven patients had thrombocytopenia; six patients had severe neutropenia. All of these adverse events recovered spontaneously. The overall incidence of delayed graft function was 24%. At 1 yr patient and graft survival were 98 and 95%, respectively, and creatinine was 135 +/- 43 micromol/L. Clinically suspected and biopsy-proven acute rejection were observed in 65 patients (27%) and 34 patients (14%), respectively. There were 62 non-cytomegalovirus (CMV) infections (two fatal) and 81 episodes of CMV infections. Eight malignancies were reported; two possibly related to immunosuppression., Conclusions: These results demonstrate that anti-thymocyte globulin has a safety profile with good tolerability and excellent efficacy.