Number Needed To Treat As A Tool For Cost Effectiveness Analysis: A Case Study In Renal Transplantation

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.

Application of daclizumab as an immune induction therapy after liver transplantation / 中国组织工程研究

BACKGROUND:Daclizumab can be special y combined with the inerleukin-2 receptor on the surface of activated T cells in human body, and this method can reflect the close of interleukin-2 receptor thus inferring the effect of induction therapy. At present, the daclizumab has been widely used in renal transplantation, but there is no consensus on its clinical application in liver transplantation. OBJECTIVE:To investigate the expression of serum CD25+T cells and soluble interleukin-2 receptor in the patients receiving daclizumab for liver transplantation during perioperative period. METHODS:A total of 58 patients received orthotopic liver transplant for the first time were included and then the patients were randomly divided into two groups:control group (n=28) and treatment group (n=30). The patients in the two groups were treated with tacrolimus, mycophenolate mofetil and corticosteroids triple immunosuppressive regimen. The patients in the treatment group received immune induction therapy with daclizumab, and the patients in the control group did not receive daclizumab. RESULTS AND CONCLUSION:Flow cytometry and enzyme-linked immunosorbent assay showed the expression levels of CD25+T cells in the treatment group were significantly lower than those in the control group at different time points after liver transplantation (P<0.01);and the expression levels of soluble interleukin-2 receptor in the treatment group were lower than those in the control group during transplantation and at the first day after transplantation (P<0.05, P<0.01). At 6 months after transplantation, the incidence of acute rejection was decreased in the treatment group (P<0.01). The results indicate that daclizumab can effectively suppress the expression level of CD25+T cells, as wel as the expression level of soluble interleukin-2 receptor in the peripheral blood in the early stage of liver transplantation, thus effectively reducing the rate of acute rejection.

The Efficacy and Safety of an Immunosuppressive Regimen Including the Use of Mycophenolate Mofetil and an Interleukin-2 Monoclonal Antibody in Heart Transplant Patients

BACKGROUND AND OBJECTIVES: An immunosuppressive regimen including the use of mycophenolate mofetil (MMF) and an interleukin-2 monoclonal antibody (IL2mAb) has shown promise to prevent acute rejection after heart transplantation. There has been a lack of report on the evaluation of the efficacy and safety of this regimen in patients receiving heart transplants in Korea. SUBJECTS AND METHODS: From November 1992 to December 2003, 111 consecutive patients who had received heart transplants in our institute were classified into two groups: patients who received the immunosuppressive regimen with MMF and an IL2mAb (group A, n=51) and patients who did not receive the regimen (group B, n=60). We compared the clinical outcomes of patients in each group including the survival rate and the occurrence of acute rejection and infection at 24 months post transplantation. RESULTS: Both drugs were tolearated in all patients except in 5 patients who complained of gastrointestinal side effects due to MMF. Despite a longer ischemic time (137.4+/-54.6 vs. 92.3+/-25.8 hours, p<0.05) and a lower serum level of cyclosporine (212.3+/-66.8 vs. 259.1+/-62.1 ng/mL, p<0.05), the rate of treatment for acute rejection was lower in group A than in group B (16% vs. 53%, p<0.05). In addition, the median time to the first treatment for acute rejection was almost twice as long for group A as for group B (91 vs. 43 days, p<0.05). The 2-year survival rate and the incidence of major infection requiring hospitalization in both groups were 94% vs. 88% and 26% vs. 21%, respectively, which were not statistically different. CONCLUSION: An immunosuppressive regimen including the use of MMF and an IL2mAb is efficacious and safe as a prophylaxis against acute rejection without the increased risk of major infection in patients who have received heart transplants in Korea.

Avances en inmunosupresión en trasplante hepático / Advances in immunossuppression in liver transplantation

The history of Immunosuppresslon is a long one. From the utilization of steroids and azathloptlne In the 50's to the design of humanized molecules that specifically block cell surface receptors. Liver transplantation is one of the procedures that benefit the most with the development of new immunosuppressors and is also one of the reasons to create a new branch in research and clinical practice: transplant medicine. It also set the standards for research in the "immunologic tolerance" field. The cornerstone in the post-liver transplant stage is the utilization of calcineurin inhibitors combined with new anti-metabolites and monoclonal antibodies. All these settings conforms a promising field in the research of new and better immunosuppressing agents.

Se ha recorrido mucho camino desde el diseño de la inmunosupresión en la década de los 50's. Desde la utilización de los esteroides y la azatioprina hasta el desarrollo de moléculas humanizadas, que bloquean específicamente receptores de superficie celular para inducir tolerancia del injerto, ha transcurrido medio siglo. El trasplante hepático ha sido uno de los procedimientos más beneficiados con el desarrollo de las nuevas drogas inmunosupresoras y ha dado origen a una nueva rama de la medicina: la medicina de trasplantes. También ha sentado las bases de investigación tendiente a lograr la "tolerancia inmunológica" del órgano trasplantado. La piedra angular en la inmunosupresión postrasplante hepático es la utilización de los inhibidores de calcineurina que, en combinación con nuevos antimetabolitos y anticuerpos monoclonales, dibujan un futuro promisorio en la búsqueda de mejores agentes.

62 case reports of using Daclizumab after renal transplantation / 中华器官移植杂志

Objective To investigate the efficacy and safety of anti CD25 Ab (Zenapax;Daclizumab) induction therapy in 62 patients following renal transplantation. Methods Sixty-two renal transplant recipients treated with Daclizumab induction therapy were analyzed retrospectively from Sep. 1999 to May 2004. Main immunosuppressive therapy regimen consisted of steroids cyclosporine and mycophenolate mofetil in all recipients after operation. According to Daclizumab dosage, these recipients were divided into 1-dose group, 2-dose group and over 2-dose group. All patients received Daclizumab 1 h before operation.Results The patients subject to Daclizumab were followed up from 3 months to 57 months. Seven of them had acute rejection ( 11.3 %) at intervals for 10.3 months, from 2 months to 14 months. Patient who had acute rejection at 10th month after operation lost his graft at 13th month after transplantation for graft dysfunction. The incidence of acute rejection was 15.6 % among 45 patients followed up over 12 months. Conclusions Induction therapy of Daclizumab could decrease the incidence of acure rejection, delay the time of acute rejection and relieve the severity of rejection. More graft can be long-survival. We can lower the dosage of CsA effectively and safely after induction of Daclizumab.

Clinical trial of daclizumab in living renal transplantation / 대한내과학회지

BACKGROUN: Despite improvements in immunosuppressive therapy for use in renal transplantation, acute graft rejection remains a risk factor of chronic rejection and a major cause of graft loss and patient death. Recently, daclizumab, an anti IL-2 receptor monoclonal antibody has been shown to reduce the incidence of acute rejection. METHODS: To investigate the immunosuppressive effect of daclizumab and the incidence of acute rejection, we administered daclizumab intravenously (1 mg/kg of body weight within 24 hours before transplantation and once every other week afterward, for a total of 5 doses) in combination with cyclosporine microemulsion (CsA), steroid and mycophenolate mofetil (MMF) to 68 transplant recipients RESULTS: Among them 62 were undergoing their first transplantation and 6 were undergoing their second transplantation. 32 patients received living-related transplants and 36 patients received living-unrelated transplants: their HLA match were as follows:1 case with 1 Ag match, 13 cases with 2 Ag matches, 18 cases with 3 Ag matches, 3 cases with 4 Ag matches, 1 case with 5 Ag matches. The clinical characteristics of patients treated with daclizumab were as follows: 42 were male, 26 were female; the mean age of recipients was 42.94 +/- 11.2 years and that of donor was 34.1 +/- 9.9 years. The underlying renal diseases were glomerulonephritis (n=47), reflux nephropathy (n=6), diabetic nephropathy (n=12), polycystic kidney disease (n=2) and acute renal failure (n=1). During the observed period (17.41 +/- 4.34 months; min. 6 months, max. 26 months), 2 cases had acute rejection in the third month after transplantation and 1 case in the 6th month after transplantation, 1 case in the 24th month after transplantation (4/68, 5.8%). In the historical control, 20.8% of acute rejection (10/48) were noted in CsA, MMF and steroid regimen group and 36% of acute rejection (22/60) in CsA, azathioprine and steroid group. Serum creatinine level was 1.21 +/- 0.23, 1.31 +/- 0.25, 1.35 +/- 0.28 and 1.34 +/- 0.31 (mg/dL) during the 1st, 3rd, 6th month and 1 year after transplantation respectively. 10 patients developed herpes-zoster infection and 6 patients had CMV infection. 1 patient expired due to CMV pneumonitis on the 3 months after transplantation. The 2-year graft survival rate was 98.5% with daclizumab and 45 months graft survival rates were 92.9% and 89.3% for MMF group and azathioprine group respectively. CONCLUSION: Daclizumab, used in combination with CsA, MMF and steroid, reduced acute rejection episodes without serious short term side effects. Further observation is needed to evaluate the graft survival rate and uncover any long-term side effects.

Basiliximab vs daclizumab for prevention of acute rejection in renal transplantation / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of two-dose basiliximab vs two-dose daclizumab for prevention of acute rejection in renal transplantation. Methods A total of 58 renal transplant recipients were randomized into 2 groups:basiliximab group ( n =30) and daclizumab group ( n =28).All the cases received the triple therapy of cyclosporine,mycophenolate mofetil and prednisolone (CsA+MMF+Pred).The 3 medications were administered as follows.For CsA,initial dose of 6 mg/kg per day was downtitrated to 4～5 mg/kg per day at 3 months,then to 3～4 mg/kg per day at 6 months.For MMF,initial dose of 0.5 g,3 times per day was downtitrated to 0.5 g,twice per day at 1 month.For Pred,initial dose of 30 mg per day was downtitrated to 20 mg per day at 3 weeks,then to 10～15 mg per day at 6 months.Basiliximab group received two-dose basiliximab (20 mg intravenous infusion) 2 hours before operation and 4 days after transplantation.Daclizumab group received two-dose daclizumab (50 mg) 1 day before operation and 14 days after transplantation.Postoperatively,acute rejection was monitored for 6 months,and adverse events and person/allograft survival were observed for 6～12 months.CD25 + cell count was tested using Beckman Coulter flow cytometer before operation and postoperatively once a week for 2 months. Results During 6-month follow-up, the number of acute rejection episodes were 5 in daclizumab group and none in basiliximab group ( P

The use of daclizumab in liver transplantation patients / 中国普通外科杂志

Objective To evaluate the efficacy and safety of daclizumab(zenapax) in liver transplantation patients with renal insufficiency. Methods We reviewed the use of daclizumab in 50 patients with renal insufficiency or at high risk of renal insufficiency during the period of liver transplantation between March 2001 to February 2003. The control group included 62 cases with no renal insufficiency at the same period. Results Renal function was recovered in 36 of 37 patients. The administration of daclizumab caused no vital organ dysfunction. Acute rejection was 6% (3/50) vs. 29 % (18/62) (P=0.826), infection was 56% (28/50) vs. 58% (36/62)(P=0.826). Conclusion Immunoprophylaxis with daclizumab regimen is safe, effective and well tolerated, and does not lead to increased opportunistic infections, and helps in improving renal function, by reducing the dosage and postponing the application of calcineurin inhibitor.

Prevention of rejection by Simulect (basiliximab) in sensitized kidney allograft recipients / 中华器官移植杂志

Objective To explore the validity and security of Simulect (basiliximab) induction immunosuppressive therapy in terms of prevention of acute allograft rejection in sensitive recipients.Methods Thirty-six adult recipients of cadaveric kidney transplant with panal reactive antibody 30 %～ 50 % were assigned randomly in a 1∶1 ratio to receive either two doses Simulect or matching placebo. Both patient groups also received baseline triple immunosuppression with the cyclosporine microemulsion, MMF and steroids. A total 40 mg Simulect was given in two doses of 20 mg eachon day 0 about 2 h before transplantation and the day 4 after transplantation respectively.Results No hyperacute rejection and delayed graft function occurred in the two groups. No apparent adverse and toxic events were recorded in the Simulect group. The incidence of acute rejection 3 months after transplantation was 11.1 % in Simulect group compared with 50 % in the placebo group ( 77.8 % reduction, P