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PubMed1999

Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group.

BACKGROUND: Acute rejection is still a major problem in renal transplantation and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody against the alpha-chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the efficacy of this type of immunoprophylaxis in combination with dual immunosuppression. METHODS: We studied the effect of daclizumab, a humanized monoclonal antibody against the alpha-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116 (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg) every other week. Baseline immunosuppression consisted of cyclosporine and corticosteroids. RESULTS: At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the daclizumab group (8% vs. 16%, P=0.02), and they required significantly lower mean (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the placebo group, P=0.01). Graft function was significantly better (P=0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the placebo arm. No patient in the daclizumab group had a lymphoproliferative disorder or any other form of immunosuppression-related tumor during the first year after transplant. CONCLUSIONS: Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.

Adrenal Cortex Hormones↗
PubMed1998

Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.

BACKGROUND: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. METHODS: We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. RESULTS: Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes. CONCLUSIONS: Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.

Acute Disease↗
PubMed2000

Daclizumab prevents acute rejection and improves patient survival post transplantation: 1 year pooled analysis.

Daclizumab is a genetically engineered human IgG1 monoclonal antibody specific for the alpha chain of the IL-2 receptor. A pooled analysis of two randomized, double-blind studies was performed on the efficacy and safety of daclizumab in renal transplantation, given in addition to standard immunosuppression. Patients receiving their first cadaveric renal allograft were randomized to receive 5 doses of daclizumab (n = 267) or placebo (n = 268), starting pre-operatively. Acute rejection at 1 year occurred less frequently with daclizumab (n = 74, 27.7 %) than with placebo (n = 116, 43.3%) (P = 0.0001). Fewer patients treated with daclizumab required anti-lymphocyte therapy for acute rejection (7.9 % vs. 15.3 %; P = 0.005). Mean cumulative doses of corticosteroids were lower with daclizumab (4133 mg) than with placebo (4562 mg). One year graft survival was 91.4 % with daclizumab, compared with 86.6 % on placebo (P = 0.065), with patient survival of 98.5 % and 95.1 % for daclizumab and placebo respectively (P = 0.022). Daclizumab was well tolerated. No increase in infectious episodes or lymphoproliferative disorders was observed with daclizumab. The incidence of cytomegalovirus infections was similar with daclizumab and placebo (15 % vs. 17.5 %). Therapy with daclizumab significantly reduces acute rejection in renal transplantation and improves patient survival without any increase in morbidity.

Adult↗
PubMed1999

Daclizumab: a review of its use in the prevention of acute rejection in renal transplant recipients.

UNLABELLED: The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in renal transplant recipients. It is specific for the alpha subunit (Tac/CD25) of the interleukin-2 (IL-2) receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. Daclizumab has advantages over murine antibodies to the IL-2 receptor, including improved effector function, a low potential for immunogenicity and long elimination half-life. When added to standard cyclosporin-based immunosuppressive therapy with or without azathioprine, daclizumab (1 mg/kg prior to surgery and once every 2 weeks thereafter for a total of 5 doses) significantly reduced the 6-month rate of acute rejection compared with placebo in 2 phase III studies. The mean number of rejection episodes was significantly reduced and the time to first acute rejection significantly increased in daclizumab versus placebo recipients. Patient survival at 1 year after transplantation was significantly higher with daclizumab than placebo in 1 study and showed a trend in favour of the drug in the other study. The 1-year graft survival rate tended to be greater in daclizumab than in placebo recipients in both studies, In a phase II study, acute rejection rates in patients treated with both daclizumab and mycophenolate mofetil (plus standard cyclosporin-based immunosuppression) were lower than those achieved with mycophenolate mofetil alone. Preliminary results indicate that daclizumab is also a useful agent in paediatric renal transplant recipients. Further investigation of the efficacy and tolerability of the drug in this patient group is clearly warranted. Daclizumab does not increase the incidence of adverse events when added to standard cyclosporin-based therapy. The incidence of opportunistic infections, lymphoproliferative disorders and malignancies was not increased above that seen with placebo. CONCLUSIONS: Although the effects of daclizumab on long term graft and patient survival require further investigation, available data indicate that daclizumab is an important advance in renal transplant immunosuppression, reducing acute graft rejection without affecting the tolerability of standard cyclosporin-based immunosuppression.

Acute Disease↗
PubMed2001

Daclizumab: a review of its use in the management of organ transplantation.

UNLABELLED: The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. When added to standard triple immunosuppression regimens, daclizumab significantly reduces the rate of acute rejection at 1 year in renal transplantation by 36% and there are indications that it may be effective in other solid organ transplantations. Three-year outcomes of two phase III clinical trials in renal transplantation indicate similar values for graft and patient survival between daclizumab and placebo when given in addition to triple immunosuppression; however, these pivotal trials were not designed with sufficient power to demonstrate any statistical significance. The addition of daclizumab induction shows potential in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without increasing the rate of acute graft rejection or adverse effects in renal and liver transplantation. Preliminary reports indicate that daclizumab may also be a useful agent in delayed graft function and graft versus host disease (GVHD). Further investigation of its efficacy in these groups and in children is needed. Data from clinical trials show daclizumab to be well tolerated in solid organ transplantation. It does not increase the incidence of infection, including cytomegalovirus infection, when compared with placebo or no induction groups. Preliminary comparative data with muromonab CD3 indicate that daclizumab may be associated with a lower rate of infectious complications and similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been proven to reduce acute rejection in renal transplant recipients when given in addition to traditional baseline immunosuppression. It has shown potential to reduce acute rejection in other solid organ transplants; however, well designed, randomised studies are required to confirm this. Clinical experience from trials to date indicate that daclizumab has a tolerability profile similar to placebo with no significant effect on the incidence of infection. The relative efficacy and tolerability of daclizumab compared with other induction agents has yet to be defined. Available data suggest that daclizumab may allow the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may have potential in the treatment of GVHD.

Animals↗
PubMed2003

Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation.

In phase III trials daclizumab was used in a five-dose regimen of 1 mg/kg at 2-weekly intervals, resulting in saturation of IL-2Ralpha on circulating lymphocytes for up to 120 days after renal transplantation. The purpose of this study was to evaluate daclizumab blood concentrations and the saturation of the IL-2Ralpha on the circulating lymphocytes with a limited dosing regimen of daclizumab. Twelve patients undergoing primary cadaver or living donor transplantation were randomized to either receive one dose (2 mg/kg) or two doses (2nd dose, 1 mg/kg) of daclizumab in addition to maintenance immunosuppression therapy consisting of either tacrolimus or cyclosporine, mycophenolate mofetil and prednisone. Patients were followed for 6 months after the transplantation. Pharmacokinetic and pharmacodynamic studies were performed up to 20 weeks after the transplantation. In patients treated with a single dose of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 43 +/- 7 days after the transplantation. In patients treated with two doses of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 45 +/- 13 days after the second dose for a total of 59 +/- 13 days after the transplantation. Daclizumab levels of 1 micro g/mL or greater were associated with saturation of the IL-2Ralpha on the circulating lymphocytes. In the new era of effective maintenance immunosuppression, a limited dosing regimen of daclizumab may be desired, practical and economical.

Antibodies, Monoclonal↗
PubMed2001

Daclizumab (humanized anti-IL2Ralpha mAb) prophylaxis for prevention of acute rejection in renal transplant recipients with delayed graft function.

BACKGROUND: The purpose of this retrospective study was to determine the benefits of daclizumab, (Zenapax, Roche Pharmaceuticals) a humanized anti-interleukin-2Ralpha (IL-2Ralpha) monoclonal antibody, for prevention of acute rejection in renal transplant recipients with delayed graft function (DGF). METHODS: Data from two multicenter randomized placebo-controlled trials were pooled. DGF was defined by urine output <30 cc/hour, decline in serum creatinine of <0.5 mg/dl, or the need for dialysis within the first 24 hours after transplantation. RESULTS: At one year posttransplantation, the incidence of biopsy-proven acute rejection in patients with DGF was reduced from 44% in the placebo group to 28% in the daclizumab group. (P=0.03) Prophylaxis with daclizumab also delayed the onset of the first biopsy-proven acute rejection episode in patients with DGF from 29+/-43 days in the placebo group to 73+/-70 days in the daclizumab group. (P=0.004) The graft survival rates in patients with DGF at 1 year posttransplantation were 78% in the placebo group and 82% in the daclizumab treated group. (P=ns) Three patients in the placebo-treated group with DGF experienced graft loss due to acute rejection, whereas no patients in the daclizumab-treated group with DGF had graft loss due to acute rejection. The 1-year patient survival rate in those with DGF in the placebo and daclizumab groups were 93% and 98%, respectively. (P=ns) CONCLUSIONS: Daclizumab effectively reduced the incidence and delayed the onset of biopsy-proven acute rejection in this high-risk subgroup of patients with DGF after renal transplantation. Graft and patient survival rates were similar between placebo- and daclizumab-treated patients with DGF.

Acute Disease↗
PubMed2001

Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation.

BACKGROUND: Daclizumab (Zenapax, Roche Pharmaceuticals), a humanized monoclonal antibody directed against the alpha chain of the interleukin 2 receptor, has been shown to reduce the incidence of acute rejection at 6 months after renal transplantation in two phase III clinical trials. This report presents the combined 1- and 3-year outcomes of kidney transplant recipients who participated in these two phase III clinical trials. METHODS: Data from two multicenter, randomized, placebo-controlled trials were evaluated with regard to graft survival, patient survival, incidence of malignancies (including lymphoma), renal function (serum creatinine and glomerular filtration rate [GFR]), and current maintenance immunosuppressive regimen. In addition, the impact of acute rejection and acute rejection requiring treatment with antilymphocyte therapy upon 3-year graft survival was evaluated. Daclizumab was compared to placebo on a background of cyclosporine (CsA), azathioprine, and corticosteroids (triple therapy, TT) or CsA and corticosteroids (double therapy, DT). RESULTS: Treatment with daclizumab in the pooled analysis demonstrated a significant reduction in the incidence of biopsy-proven acute rejection episodes at 12 months posttransplant (43% vs. 28%, P<0.001). The 3-year graft survival was not significantly different between placebo and daclizumab-treated patients in the TT trial (83% vs. 84%) or in the DT trial (78% vs. 82%). Pooled patient survival was excellent in both placebo- (91%) and daclizumab- (93%) treated patients. The incidence of malignancies or posttransplant lymphoproliferative disorder (PTLD) in placebo- versus daclizumab-treated groups was comparable in both clinical trials. Renal function was similar between placebo- and daclizumab-treated groups in both the TT and DT trials. The occurrence of delayed graft function, acute rejection requiring antilymphocyte therapy at 6 months, and acute rejection at 12 months posttransplant were associated with decreased graft survival rates at 3 years posttransplant. CONCLUSIONS: The beneficial effect of daclizumab prophylaxis upon the incidence of acute rejection after renal transplant with TT or with DT was not associated with adverse clinical sequelae, including the development of PTLD, at 3 years posttransplant. There was no beneficial effect of daclizumab on graft survival at 3 years, but the trial was inadequately powered to detect this. Both studies showed excellent graft and patient survival at 3 years.

Acute Disease↗
PubMed2000

Daclizumab (Zenapax) inhibits early interleukin-2 receptor signal transduction events.

Daclizumab, a humanized antibody against the interleukin-2 (IL-2) receptor (R) alpha-chain, is a promising new immunosuppressant in transplantation. As its exact mechanism of action has remained unclear, we examined its short-term effects on primary human T lymphocytes expressing the high-affinity IL-2R. Daclizumab exposure for 20 min neither affected T cell viability nor their surface expression of the IL-2R alpha-, beta-, or gamma-chains. However, after IL-2 stimulation (200 U/ml, 20 min), immunoblots of cell lysates demonstrated attenuation of the IL-2-induced tyrosine phosphorylation of 65-75 kDa proteins by Daclizumab, but not by isotype controls. Since this is the molecular weight of the IL-2R beta- and gamma-chains, which are both tyrosine-phosphorylated by IL-2, we next examined the effect of Daclizumab on their IL-2-induced tyrosine phosphorylation. In immunoblots of IL-2R beta- and gamma-chain-immunoprecipitates the tyrosine phosphorylation of both chains by IL-2, but not by IL-15, was attenuated in the presence of Daclizumab. Furthermore, co-immunoprecipitation experiments showed that Daclizumab inhibited the IL-2-induced association of these chains, a prerequisite for their mutual tyrosine phosphorylation. Lastly, we demonstrated that Daclizumab inhibits the receptor-downstream induction of the IL-2-activated DNA-binding protein STAT5 in gel shift assays. We conclude that Daclizumab directly and specifically interferes with IL-2 signaling at the receptor level by inhibiting the association and subsequent phosphorylation of the IL-2R beta- and gamma-chains induced by ligand binding. Under our experimental conditions, Daclizumab had no effects on cell viability, and it did not modulate the surface expression of the IL-2R alpha-, beta-, or gamma-chains.

Animals↗
PubMed2003

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation.

Daclizumab and mycophenolate mofetil (MMF) decrease the incidence of acute allograft rejection. This double-blind, randomized, placebo-controlled trial was performed primarily to assess the pharmacokinetics of MMF in an immunosuppressive regimen incorporating daclizumab. At five centers, 75 renal transplant recipients were randomized 2:1 to receive either daclizumab 1 mg/kg or placebo pre-transplantation and every other week, for a total of five doses. All patients received cyclosporine, steroids, and MMF. Levels of mycophenolic acid (MPA), its glucuronide metabolite, and daclizumab were measured after dosing on days 28 and 56. Safety parameters evaluated included: adverse events, laboratory abnormalities, infections, patient/graft survival, incidence of lymphoproliferative disorders, and incidence of acute rejection at 12 months. The concomitant administration of daclizumab and MMF had no effect on the pharmacokinetics of MPA: AUC(0-8) values (microg h/mL +/- SD) on day 28 were 30.1 +/- 13.3 for daclizumab-treat patients vs. 31.1 +/- 12.4 for placebo and on day 56, 37.7 +/- 18.2 for daclizumab-treated patients vs. 35.7 +/- 14.0 for placebo. Adverse events were similar between the two groups. Acute rejection at 12 months occurred in 14% of patients receiving daclizumab and 20% of patients receiving placebo. The coadministration of daclizumab did not result in a pharmacokinetic interaction with MPA, the active metabolite of MMF.

Antibodies, Monoclonal↗
PubMed2001

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function.

The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF) and steroids is a new option for initial immunosuppression in patients undergoing liver transplantation (LT) with impaired renal function. We evaluated the efficacy and safety of daclizumab in preventing rejection in 25 patients with impaired kidney function undergoing LT. Patients with serum creatinine (Cr) levels greater than 2 mg/dL immediately before LT were administered initial immunosuppression with daclizumab, 1 mg/kg, in addition to MMF, 2 g/d, and methylprednisolone. Tacrolimus was added after kidney function improved (when Cr levels improved by >25% of initial value). Daclizumab-treated patients were compared retrospectively with 2 other groups of patients who underwent LT with kidney impairment (Cr > 2 mg/dL): 56 patients were administered OKT3 induction, and 48 patients were administered low-dose tacrolimus. The incidence of rejection and infection (bacterial, fungal, and viral), need for preoperative and postoperative dialysis, Cr level immediately post-LT and at 3 months, and graft and patient survival were analyzed. There was no difference among the groups in 3-month Cr levels or the incidence of rejection or fungal or viral infection. The daclizumab group had fewer bacterial infections (n = 13) than the tacrolimus group (n = 28) and significantly fewer than the OKT3 group (n = 58; P =.006). Only 1 patient (4%) in the daclizumab group required dialysis post-LT versus 13 patients in each of the other groups (OKT3, 23.21%; P <.05; tacrolimus, 27%). In the daclizumab group, 2-year patient and graft survival rates were statistically significant compared with the low-dose tacrolimus group (89% and 81% v 73% and 69%, respectively; P =.06). There were no side effects related to daclizumab use, and all patients tolerated the drug well. In patients with impaired renal function before LT, daclizumab-based initial immunosuppression can be used safely to reduce the risk for infection and need for dialysis post-LT, with improved long-term graft and patient survival.

Adult↗
PubMed2002

Pharmacokinetics, pharmacodynamics, and immunodynamics of daclizumab in a two-dose regimen in liver transplantation.

BACKGROUND: The humanized anti-interleukin 2 receptor (IL-2R) monoclonal antibody daclizumab (Zenapax) has been shown to be safe and effective for preventing acute allograft rejection in renal transplantation. The aim of this study was to evaluate pharmacokinetics and pharmacodynamics of daclizumab in a two-dose regimen (1.5 mg/kg total) after liver transplantation. METHODS: Twenty-eight patients were enrolled in this study. Patients were evaluated for outcome, postoperative blood and ascites loss, serum levels of daclizumab, and corresponding changes in peripheral blood. Patients were also checked for development of anti-daclizumab antibodies. RESULTS: CD25+ cells in patients' blood were significantly reduced for 28 days after daclizumab application. Elimination half-life of the antibody was 99 hr with a total body clearance of 57 ml/hr. Blood loss was not statistically significant and loss of ascites was weakly correlated to the monoclonal antibody clearance. One episode of mild acute rejection occurred. Although there was no significant decrease in absolute counts of CD3+, CD4+, and CD8+ lymphocytes, we were not able to show constant coating of IL-2Ralpha with daclizumab. IL-2Ralpha was not detectable on cell surface with two different antibodies and IL-2Rbeta was clearly reduced. Low titers of neutralizing anti-daclizumab antibodies in 3 of 13 patients were not of clinical significance and without influence on the pharmacokinetics. CONCLUSIONS: A two-dose regimen with daclizumab in liver transplantation leads to effective blockade of the IL-2Ralpha for at least 14 days after transplantation. Daclizumab seems to affect not only IL-2Ralpha but also IL-2Rbeta and may lead to an impairment of other cytokine pathways, such as the IL-15 pathway.

Antibodies, Monoclonal↗
PubMed2005

Daclizumab is associated with decreased rejection and improved patient survival in renal transplant recipients.

The present study investigated the safety of induction therapy with daclizumab (compared with no induction treatment), in adult renal transplant patients reported to the Scientific Registry of Transplant Recipients (SRTR) database between January 1, 1998 and July 27, 2003. Patients who were discharged from the hospital on mycophenolate mofetil, azathioprine, or sirolimus were divided into two groups: induction treatment with daclizumab (n = 8203) and no induction treatment (n = 25,368). Patient survival, death due to infection and death due to malignancy were evaluated at 1 and 3 yr post-transplantation. Rejection and graft survival were also examined. Kaplan-Meier and Cox regression models were used to evaluate outcomes. No significant differences were found between patients treated with daclizumab compared with patients who received no induction therapy for death due to infection or malignancy at 1 and 3 yr post-transplantation. Patients treated with daclizumab (compared with no induction treatment) had statistically significantly better survival rates at 1 (96.9% vs. 96.2%, p = 0.003) and 3 yr (92.4% vs. 91.4%, p = 0.004) although absolute differences were minimal. This was confirmed in the multivariable Cox regression analysis for patient death at 1 (HR = 0.77, p < 0.001) and 3 yr (HR = 0.83, p = 0.001) post-transplantation. Patients treated with daclizumab compared to no induction had lower rejection rates at 1 (13.1% vs. 17.3%, p < 0.001) and 3 yr post-transplantation (16.7% vs. 21.3%, p < 0.001). Cox regression confirmed a decreased risk for rejection at 1 (HR = 0.74, p < 0.001) and 3 yr (HR = 0.75, p < 0.001). Treatment with daclizumab was associated with reduced risk for graft loss at 1 (HR = 0.82, p < 0.001) and 3 years (HR = 0.86, p < 0.001). In conclusion, daclizumab was associated with a significantly reduced risk for rejection and graft loss compared with no induction treatment, and improved patient survival. In addition, daclizumab was not associated with an increase in risk of death due to infection or malignancy, when compared with no induction therapy. These findings demonstrate the short and long-term safety and efficacy of daclizumab in patients transplanted between January 1998 and July 2003.

Adult↗
PubMedDate not supplied

Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study.

BACKGROUND: Addition of the interleukin-2 receptor (IL-2R) antagonists basiliximab or daclizumab to a calcineurin inhibitor-based regimen significantly reduces risk of acute rejection with a tolerability profile similar to a placebo. Use of a truncated two-dose regimen of daclizumab has been reported, but till date, there has been no controlled study of two-dose daclizumab vs. two-dose basiliximab. METHODS: Deceased-donor renal transplant recipients were randomized to basiliximab (20 mg on days 0 and 4) or daclizumab (50 mg on days 1 and 14) with cyclosporine, mycophenolate mofetil and corticosteroids. Flow cytometry was used to calculate the proportion of CD25(+) T cells in peripheral blood. RESULTS: Thirty patients were randomized to basiliximab and 28 to daclizumab. There was one patient death in each group, with no other graft losses. By six months, the incidence of biopsy-proven acute rejection was 0% with basiliximab vs. 21.4% with daclizumab (p < 0.05). Three patients in the daclizumab group required OKT3 for steroid-resistant rejection. There were no between-group differences in the incidence of infection. The proportion of CD25(+) T cells declined markedly during the first two wk in both groups, but was significantly lower in the basiliximab group during weeks six to eight. CONCLUSION: Two doses of basiliximab are more effective than two 1 mg/kg doses of daclizumab in preventing acute rejection in de novo renal transplant patients receiving cyclosporine, mycophenolate mofetil and corticosteroid maintenance therapy. In patients receiving relatively low-level immunosuppression in order to minimize toxicity, basiliximab may be preferable to a truncated daclizumab regimen.

Adult↗
PubMed2001

Reperfusion edema after lung transplantation: effect of daclizumab.

PURPOSE: To determine if daclizumab, an interleukin-2 antagonist, reduced the severity of reperfusion edema in lung transplant recipients. MATERIALS AND METHODS: Eighty-five patients who were to undergo 86 consecutive lung transplants were included; 43 (50%) received daclizumab in addition to conventional immunosuppression. Patients were assigned to one of the following groups: control, right allograft; control, left allograft; daclizumab treated, right allograft; daclizumab treated, left allograft. Radiographs obtained in the first 5 postoperative days were evaluated for degree of edema. Mean daily edema scores and curves for control and daclizumab-treated groups were compared. Differences in survival at 1, 3, 6, and 12 months after transplantation, days of mechanical ventilation, and the ratio of arterial oxygenation to inspired oxygen level at 1, 3, and 5 days after transplantation were also compared. RESULTS: Mean daily edema scores, edema curves, survival, days of mechanical ventilation, and ratio of arterial oxygenation to inspired oxygen level at 1 and 3 days after transplantation did not significantly differ between daclizumab-treated and control groups. A trend toward improved survival in the daclizumab-treated group was noted. CONCLUSION: Daclizumab had no effect on the radiographic or immediate clinical manifestations of reperfusion edema in lung transplant recipients. Additional follow-up is needed to determine if daclizumab offers any long-term benefit in terms of reduced rejection rates or survival.

Adolescent↗
PubMed2001

Cyclosporine-associated thrombotic microangiopathy during daclizumab induction: a suggested therapeutic approach.

A woman on daclizumab developed thrombotic microangiopathy secondary to cyclosporine after a living-unrelated kidney transplant. Despite cyclosporine discontinuation, hemolysis persisted. The second dose of daclizumab was postponed 24 h, and after a maximum of two sessions of plasmapheresis (to avoid further modifications in daclizumab schedule) with plasma exchange, daclizumab was administered. Plasma infusions were prescribed until D-dimer and fibrinogen-degradation products normalized; thereafter, FK-506 was started without recurrence of the hemolytic picture and renal function restored. This observation suggests that in patients on daclizumab who develop thrombotic microangiopathy secondary to immunosuppressants, if discontinuation of the offending drug is unsuccessful, plasmapheresis with plasma exchange can be performed when the lowest levels of daclizumab exist, followed by daclizumab infusion. Plasma prescription must be continued thereafter until D-dimer and figrinogen-degradation products normalize. However, if hemolysis persists when daclizumab levels are high, plasma infusions are useful and plasmapheresis avoided. FK-506 administration did not result in recurrence of hemolysis during daclizumab induction.

Antibodies, Monoclonal↗
PubMed2005

Induction therapy after cardiac transplantation: a comparison of anti-thymocyte globulin and daclizumab in the prevention of acute rejection.

BACKGROUND: Induction therapy with antibodies decreases and delays early allograft rejection. We compared the safety and efficacy of daclizumab and anti-thymocyte globulin (ATG) with respect to the frequency and severity of acute cardiac allograft rejection in heart transplant recipients. METHODS: Forty sequential adult patients were retrospectively studied. In the first 20 patients ATG (2.5 mg/kg daily for 3 to 5 days peri-/and post-operatively) was used as induction therapy and, in the remaining 20 patients, daclizumab (1 mg/kg peri-operatively and every 2 weeks thereafter for a total of 5 doses) was used. A standard triple-drug immunosuppression regimen was administered to all patients. RESULTS: Baseline characteristics and trough levels of cyclosporine in the 2 groups were similar. During the induction period, defined as the first 3 months, 12 acute rejection episodes requiring treatment (ISHLT Grade > or =2) occurred in the ATG group and 9 in the daclizumab group (p > 0.05). However, the number of biopsies with Grade 1 rejection was increased >2-fold in the daclizumab group (n = 35) compared with the ATG group (n = 17; p = 0.04). The total number of biopsies performed within the first 3 months increased by 26% in the daclizumab group. The number and severity of rejection episodes after 3 months was similar in the 2 groups. The overall occurrence of bacterial infections was significantly higher in the ATG group than in the daclizumab group (p = 0.05). CONCLUSIONS: ATG and daclizumab are equally effective in preventing acute rejections requiring treatment (ISHLT Grade > or =2). Due to the significantly greater frequency of Grade 1 rejections, daclizumab was found to be associated with an increased number of additional biopsies for monitoring rejection status. This implies additional costs to the transplant program, and the long-term implications of the increased number of low-grade rejection episodes remains to be determined.

Adult↗
PubMed2005

Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids.

BACKGROUND: Sparse published data exist on outcomes in daclizumab-treated cardiac transplant patients. One trial observed an increased mortality risk 6 and 12 months posttransplant in patients receiving daclizumab plus mycophenolate mofetil (MMF), cyclosporine, and steroids. This study further investigates the safety profile of daclizumab with this same immunosuppressive regimen from a large registry. METHODS: Data obtained at hospital discharge on all adult cardiac transplants performed in the USA between January 1998 and October 2003 for patients receiving MMF plus cyclosporine and steroids were accessed from the Scientific Registry of Transplant Recipients. Patients were selected based on induction treatment: daclizumab (n = 684) or no induction (n = 2525). Outcomes were evaluated at 6 months, 12 months, and 3 years posttransplant. Univariate Kaplan-Meier and multivariate Cox models were used to evaluate the effect of treatment on outcomes. Patient survival and infectious death were the primary endpoints. Secondary endpoints included rejection within the first year posttransplant (acute rejection; AR) and total rejection episodes over time. The two treatment groups shared similar demographics and transplant procedure details. RESULTS: Daclizumab (vs no induction) patients had no increased risk of patient death nor infectious death. Daclizumab patients had a lower incidence of AR at 6 months (P = .005) and 12 months (P < .001); the adjusted risk for AR at 12 months (hazards ratio [HR] = 0.77; P = .89) and over 3 years (HR 0.83, P = .006) was also lower in daclizumab-treated patients. CONCLUSIONS: In cardiac transplant patients, daclizumab (vs no induction) does not result in increased mortality or infectious death, and is associated with a lower incidence of AR.

Adult↗