PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Basiliximab”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2001

Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients.

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.2 microg/mL as confirmed by flow cytometry measurements. Basiliximab clearance was 29+/-14 mL/h when coadministered with azathioprine and 18+/-8 mL/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37+/-15 mL/h from a previous study of basiliximab with dual therapy (p<0.001). As a consequence of the lower clearance of basiliximab, the durations of CD25 saturation were prolonged in the presence of azathioprine (50+/-20 d; range, 13--84) and mycophenolate mofetil (59+/-17 d; range, 28--94) compared with dual therapy (36+/-14 d; range, 12--91). A total of 27 acute rejection episodes occurred during the first 6 months in the two studies. Durations of CD25 saturation were not different in these patients compared with those who remained rejection-free in each study. A single patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 39 and 64% in the presence of azathioprine and mycophenolate mofetil, respectively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basiliximab. Nonetheless, the range of CD25 saturation durations and basiliximab clearances did not extend outside the range when basiliximab was used with dual therapy in the absence of these agents. Hence, no dosing adjustment is deemed necessary when basiliximab is used in triple immunosuppressive therapy including either azathioprine or mycophenolate mofetil.

Antibodies, Anti-Idiotypic↗
PubMed1999

Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group.

BACKGROUND: A double-blind, placebo-controlled phase III study was performed to assess whether basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection episodes in renal allograft recipients. METHODS: A total of 348 patients were randomized into two demographically matched, equally sized groups treated with either basiliximab or placebo. The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to block detection of interleukin-2 receptor on 97% of peripheral blood lymphocytes for 30-45 days. All patients received immunosuppressive therapy with cyclosporine microemulsion (Neoral) and steroids. An intent-to-treat analysis of 1-year data assessed the incidence of posttransplant acute rejection episodes, patient and graft survival rates, and the safety and tolerability of basiliximab. RESULTS: Among the eligible 346 patients equally divided into the two treatment groups, basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab vs. 85 (49.1%) placebo (P=0.009). Graft losses occurred in 9 (5.2%) basiliximab-treated and 12 (6.9%) placebo-treated patients. Five (2.9%) deaths in the basiliximab group and seven (4.0%) in the placebo group occurred. Compared with placebo, a higher fraction of basiliximab patients produced urine in the operating room, and a significantly lower fraction had renal dysfunction in the first month (serum creatinine > or =5 mg(dl) and between 1 and 12 months (serum creatinine > or =3 mg/dl). During the first 12 months, 94 (54%) basiliximab-treated patients experienced serious adverse events, compared with 106 (61%) who received placebo. CONCLUSIONS: Prophylactic basiliximab therapy is well tolerated, has an adverse event profile comparable to placebo, and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation.

Acute Disease↗
PubMed1999

Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. The U.S. Simulect Renal Transplant Study Group.

BACKGROUND: Basiliximab is an interleukin-2 receptor (CD25) chimeric monoclonal antibody used for acute rejection prophylaxis in renal transplants. In the context of a randomized, double-blind efficacy trial, its population pharmacokinetics and potential exposure-response relationships were explored in de novo kidney allograft recipients receiving 40 mg basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppressive therapy with cyclosporine microemulsion and corticosteroids. METHODS: Serial blood samples (8.2+/-1.3 per patient) were collected over 12 weeks after transplant from 169 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. The duration of CD25 saturation was estimated as the time over which serum basiliximab concentrations exceeded 0.2 microg/ml. The relationships between pharmacokinetic parameters and demographic-clinical covariates were explored by regression methods and unpaired t-tests. RESULTS: Basiliximab clearance was 36.7+/-15.2 ml/hr, distribution volume 8.0+/-2.4 L, and half life 7.4+/-3.0 days. Patient weight (range, 44-131 kg) and age (range, 20-69 yrs) each contributed < or =6% to the variability in clearance and volume. Gender, ethnic group, and the presence of proteinuria had no clinically relevant influences on basiliximab disposition. Receptor-saturating basiliximab concentrations were maintained for 36+/-14 days (range, 12-91). There was no apparent relationship between the incidence or day of onset of acute rejection episodes during CD25 saturation and basiliximab concentration (range, 0.2-5.0 microg/ml). In patients who experienced a rejection episode after basiliximab was eliminated from serum (n=33), basiliximab had not been cleared faster than in their rejection-free peers (P=0.322) nor had CD25 been saturated for a shorter period of time (33+/-13 days vs. 37+/-14 days for rejection-free patients, P=0.162). CONCLUSIONS: There were no demographic or clinical subpopulations not adequately treated with the standard basiliximab dosing regimen. Over the range of CD25 suppression durations observed in this study, extended periods of receptor blockade did not seem to confer an immunoprophylactic advantage compared with shorter periods of receptor suppression.

Adult↗
PubMed1997

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.

Acute Disease↗
PubMed1999

Screening for basiliximab exposure-response relationships in renal allotransplantation.

The immunosuppressant basiliximab--a chimeric monoclonal antibody specific to the interleukin-2 receptor on activated T-lymphocytes--significantly reduces the incidence of acute cellular rejection following renal transplantation. Screening for exposure-response relationships was performed within a randomized, blinded, placebo-controlled efficacy trial in which patients received 40 mg basiliximab (20 mg on days 0 and 4) by intravenous infusion in addition to cyclosporine and corticosteroids. In a subset of patients, serum samples were collected pre-transplant and once in weeks 2, 3 and 4 for determination of basiliximab concentrations. A population pharmacostatistical model was used to derive individual empirical Bayes estimates of each patient's pharmacokinetic parameters. Biopsy-confirmed acute rejection episodes were recorded to month 6 post-transplant. Forty basiliximab-treated patients were evaluated, 30 men and 10 women, aged 48 +/- 12 yr (range, 24-73) and weighing 72.4 +/- 12.9 kg (range, 52.5-107.5). The basiliximab distribution volume was 7.5 +/- 1.7 L, the half-life 7.5 +/- 2.5 d and the clearance 33 +/- 12 mL/h. There was no clinically relevant influence of weight, age, or gender on basiliximab disposition. Receptor-saturating serum basiliximab concentrations (> 0.2 microgram/mL) were maintained for 41 +/- 23 d. Twenty-five patients remained rejection-free over the 6-month observation period, while a total of 26 biopsy-confirmed acute rejection episodes occurred in the remaining 14 patients. Of these episodes, 12 occurred during receptor blockade. No apparent relationship to basiliximab concentration on the day of onset was observed range, 0.1-9.0 microgram/mL) nor did the time of suppression offset represent a period of increased risk for rejection episodes. Fourteen rejection episodes occurred after basiliximab had cleared from the serum. The durations of receptor suppression preceding these events did not differ compared with those in patients who remained rejection-free: 32 +/- 11 versus 45 +/- 26 d, respectively (p = 0.1269). Given the durations of receptor saturation achieved with the chosen basiliximab regimen, this screen for exposure-response relationships did not identify the duration of receptor saturation in peripheral blood as a predictive factor for acute rejection episodes. Further exploration for exposure-effect relationships in a larger population is warranted.

Adult↗
PubMed2000

A prospective economic evaluation of basiliximab (Simulect) therapy following renal transplantation.

BACKGROUND: Immunoprophylaxis with basiliximab (Simulect), an anti-interleukin-2-receptor (anti-IL-2R; CD25) chimeric monoclonal antibody, has been demonstrated to significantly reduce the incidence of acute cellular rejection in adult renal allograft recipients (32% vs. placebo, p < 0.01). METHODS: An economic evaluation was conducted as part of a U.S. multi-center, randomized, double-blind, placebo-controlled clinical trial comparing basiliximab plus dual immunosuppressive therapy (cyclosporine modified [Neoral] and corticosteroids) to dual therapy alone. Healthcare resources utilized by the 346 subjects in the 'intent-to-treat' population were prospectively collected over the 1-yr study period. Direct medical costs were determined for all hospitalizations, outpatient provider visits, procedures (excluding the initial transplant procedure), laboratory and diagnostic tests, and immunosuppressants, including basiliximab when administered. RESULTS: Total first-year medical costs were lower for the basiliximab group than for the placebo group ($28 927 vs. $32 300, difference = $3373). although this difference was not statistically significant. First-year hospital costs for treating acute rejection were also lower for the basiliximab group ($9328 vs. $10761, difference = $1433); however, this difference did not achieve statistical significance. Importantly, the efficacy analysis demonstrated a significant reduction in the incidence of acute rejection (38 vs. 55%, p < 0.01) in the basiliximab arm, and this was accomplished without increasing the overall cost of care. Fewer basiliximab-treated patients (8 vs. 15%,, p = 0.03) were hospitalized. This observation suggested less serious illness and reduced treatment costs among basiliximab-treated patients, because the overall incidence of infection was similar between the groups. The adverse event profile of patients receiving basiliximab was clinically and economically indistinguishable from that of those treated with placebo. CONCLUSION: Induction immunosuppression with basiliximab, combined with cyclosporine modified and corticosteroids, was therapeutically beneficial and contained medical costs during the initial post-transplant year.

Adrenal Cortex Hormones↗
PubMed1999

Basiliximab.

The chimaeric monoclonal antibody basiliximab specifically binds the alpha subunit of the interleukin-2 (IL-2) receptor on activated T lymphocytes. Through competitive antagonism of IL-2, basiliximab supplements standard immunosuppressive therapy after renal transplantation. < or =24 Hours after a single intravenous dose of basiliximab 2.5 to 25 mg, approximately 90% of available IL-2 receptors on T lymphocytes were complexed with the drug. This level of basiliximab binding was maintained for 4 to 6 weeks when renal transplant patients received basiliximab 20 mg 2 hours before and then 4 days after transplantation surgery. In 2 large, well-designed trials, the percentage of patients with biopsy-confirmed acute rejection episodes after renal transplantation was significantly lower with basiliximab 20 mg (administered 2 hours before and then 4 days after transplantation surgery; 30 or 33%, respectively) than placebo (44 or 46%) at 6 months after surgery. Basiliximab was well tolerated during clinical trials. The incidence of infections (including active cytomegalovirus infection) and post-transplant lymphoproliferative disorders was similar with basiliximab and placebo. Cytokine release syndrome was not observed in patients who received basiliximab.

Animals↗
PubMed2001

A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation.

BACKGROUND: Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. METHODS: Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods. RESULTS: Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity, and notable postoperative bleeding had no clinically relevant influences on basiliximab disposition; however, the cumulative volume of drained ascites fluid in the first week was positively correlated with clearance. Receptor-saturating basiliximab concentrations (> or =0.1 microg/mL) were maintained for 38 +/- 16 days, and this was negatively correlated with the cumulative volume of drained ascites fluid in week 1. Patients who experienced an acute rejection episode did not clear basiliximab at a faster rate than their rejection-free peers nor did they maintain CD25-saturating concentrations for a shorter period. CONCLUSIONS: Although the standard dose regimen of 20 mg of basiliximab on days 0 and 4 after transplantation appears to be appropriate for the majority of patients with liver transplants, a supplemental dose at the end of the first week may be considered for those with substantial (>10 L) postoperative ascites fluid drainage.

Antibodies, Anti-Idiotypic↗
PubMed2001

Removal of basiliximab by plasmapheresis.

Basiliximab is a chimeric monoclonal antibody directed against the alpha chain of interleukin-2 (IL-2) receptors. Given its expected volume of distribution (plasma volume), therapeutic plasmapheresis may be expected to lower serum Basiliximab levels. A 20-mg dose of Basiliximab was given before plasmapheresis. Blood and pheresis fluid samples were obtained to monitor Basiliximab levels. A total of three blood samples were drawn: the first was obtained 4 hours before, the second sample immediately before commencement, and the third 2 hours after cessation of plasmapheresis. A fourth sample was obtained from the removed plasma. There was an appreciable reduction in Basiliximab concentration levels after plasmapheresis. From the change in serum concentration after plasmapheresis, approximately 64.6% of circulating Basiliximab was removed. Plasmapheresis removes substantial amounts of Basiliximab. Therefore, supplemental Basiliximab should be given after plasmapheresis to maintain the desired duration of IL-2R saturation.

Antibodies, Monoclonal↗
PubMed2001

An economic and quality-of-life assessment of basiliximab vs antithymocyte globulin immunoprophylaxis in renal transplantation.

BACKGROUND: Immunosuppressive therapy with cyclosporin A has substantially improved clinical outcomes for renal transplantation. Whether basiliximab (a chimeric monoclonal antibody) demonstrates economic and quality-of-life advantages over other induction therapies has not yet been shown. METHODS: A multi-centre open-label clinical trial was conducted among renal transplant recipients in the US, in which patients were randomized into two induction therapy regimens: basiliximab and antithymocyte globulin (ATG) as part of a quadruple immunosuppressive regimen. Medical resources used and a EuroQol visual analogue scale (VAS) rating of quality of life were collected prospectively for the 135 dosed subjects for a period of 1 year post-treatment. We analysed the differences between treatment groups in 1-year costs and 1-year quality-adjusted survival. We also conducted a post hoc analysis of outcomes among the subgroup of patients identified as high risk. RESULTS: A significant difference was observed in first-year post-treatment costs (basiliximab, $45857; ATG, $54729; difference, $8872 (95% CI, $1169 to $16573). The savings from basiliximab can be attributed to the less expensive induction therapy (basiliximab, $2378; ATG, $8670; difference, $6292 (95% CI, $5165 to $7419)) and other savings during the initial hospitalization totalling $2609. One-year quality-adjusted survival was the same in both groups (basiliximab, 81.5; ATG, 81.1; difference, 0.45 (95% CI, -5.9 to 6.8)). The results of the post hoc analysis of the 48 high-risk patients were comparable to the analysis of all patients. CONCLUSIONS: These results demonstrate lower first-year post-treatment costs in renal-transplant recipients receiving basiliximab compared to ATG with no differences in quality-adjusted survival. The results also suggest similar differences among high-risk subjects.

Antibodies, Monoclonal↗
PubMed2000

Reduced acute rejection and superior 1-year renal allograft survival with basiliximab in patients with diabetes mellitus. The Global Simulect Study Group.

BACKGROUND: Renal allograft recipients with diabetes mellitus often demonstrate poorer clinical outcomes than nondiabetic patients. Basiliximab (Simulect), a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection in renal allograft recipients in 2 multicenter, placebo-controlled, phase III trials. METHODS: An analysis of pooled results from the 2 trials was conducted to compare the efficacy and safety of basiliximab with placebo in renal transplant recipients with and without prior diabetes. Patients received either basiliximab (20 mg on day 0 and day 4 posttransplantation) or placebo in combination with cyclosporine for microemulsion (Neoral) and steroids. RESULTS: A total of 722 patients (150 diabetic, 572 nondiabetic) were eligible for intent-to-treat analysis. At 12 months, basiliximab as compared with placebo reduced the proportion of patients experiencing first acute rejection by 41% in diabetics (P<0.01) and by 29% in nondiabetics (P<0.001). Biopsy-confirmed rejection was reduced by 44% in diabetics (P<0.01) and by 26% in nondiabetics (P<0.01). The first acute rejection episode requiring augmented immunosuppression other than steroids was reduced by 49% in diabetics (P<0.01) and by 41% in nondiabetics (P<0.001); death, graft loss, or first rejection episode was reduced by 43% in diabetics (P=0.001) and by 22% in nondiabetics (P<0.01). Superior graft survival was maintained in diabetic recipients treated with basiliximab versus placebo (96% vs. 86%; P=0.022). There were no significant differences in safety between basiliximab and placebo in both diabetic and nondiabetic patients. CONCLUSIONS: Basiliximab is associated with a significant reduction in acute rejection and an excellent safety profile in renal transplant recipients with and without diabetes mellitus. Superior graft survival was evident in diabetic patients.

Acute Disease↗
PubMed1997

Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts.

BACKGROUND: Basiliximab is an interleukin-2 receptor (IL-2R; CD25) chimeric monoclonal antibody for immunoprophylaxis against acute rejection in renal transplantation. Its pharmacokinetics were characterized in a multicenter open-label, prospective dose-escalation study to identify a single-dose regimen providing IL-2R-saturating serum concentrations in the critical first posttransplant month. METHODS: Thirty-two recipients of primary, mismatched cadaver kidneys were enrolled: 20 men and 12 women, who were 47+/-11 years old and weighed 65+/-12 kg. The immunosuppression regimen consisted of steroids and azathioprine from day 0 and cyclosporine from day 10. Basiliximab was infused over 30 min as a single dose preoperatively. RESULTS: Thirty patients were evaluable for basiliximab pharmacokinetics: 24 received 40 mg and 6 received 60 mg. Basiliximab was well tolerated without evidence of cytokine-release syndrome, hypersensitivity reactions, or anti-idiotype antibody response. Peak concentration and area under the concentration curve increased proportionally with dose. Postinfusion concentrations declined in a biphasic manner with a terminal half-life of 6.5+/-2.1 days. Weak, widely dispersed correlations were noted between body weight versus distribution volume (r=0.29) and versus clearance (r=0.45), suggesting no clinical relevance for weight-adjusted dosing. There were no apparent gender-related differences in basiliximab disposition. Previous phase II data indicated that serum concentrations in excess of 0.2 microg/ml are sufficient to saturate IL-2R epitopes on circulating T lymphocytes. Concentrations were above this threshold for 26+/-8 days (range 16 to 46) at the 40-mg dose level and for 32+/-11 days (range 22 to 51) at the 60-mg dose level. CONCLUSIONS: Total basiliximab doses of 40-60 mg were well tolerated, nonimmunogenic, and estimated to provide immunoprophylaxis to cover the first posttransplant month.

Adult↗
PubMed1998

Disposition and immunodynamics of basiliximab in liver allograft recipients.

A randomized, open-label prospective study was conducted with recipients of primary cadaveric liver allografts to characterize the disposition and immunodynamics of basiliximab, an interleukin-2 receptor, alpha-chain chimeric monoclonal antibody for immunoprophylaxis of acute rejection. Patients received a total intravenous dose of 40 mg basiliximab in addition to baseline dual immunosuppression consisting of cyclosporine (INN, ciclosporin) and steroids. The central distribution volume was 5.6 +/- 1.7 L with a steady-state volume of 7.5 +/- 2.5 L. It was cleared slowly with a total body clearance of 75 +/- 24 ml/hr and an elimination half-life of 4.1 +/- 2.1 days. Basiliximab was measurable in drained ascites fluid, and clearance by this route was an average of 20% of total clearance. Total body clearance correlated positively with volume of postoperative blood loss (r = 0.5253, p = 0.0101), suggesting that bleeding may represent an additional route of drug removal. A threshold relation was observed between serum concentration of basiliximab and CD25 expression on T lymphocytes whereby complete saturation of interleukin-2 receptor alpha-chain was maintained as long as serum concentrations exceeded 0.1 microgram/ml. The duration of receptor saturation was 23 +/- 7 days after transplantation (range, 13 to 41 days).

Adolescent↗
PubMed2000

[Daclizumab and basiliximab: monoclonal mouse-man antibodies with effective immunosuppression without side effects].

Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab, when added to an immunosuppressive regimen consisting of cyclosporin and prednisone, reduce the incidence of acute rejections after kidney transplantation by 30-40%, during the first 6 months. Daclizumab and basiliximab are monoclonal antibodies of which the variable parts are of mouse origin and the other components of human origin. The addition of the interleukin-2 receptor antagonists was not accompanied by extra side effects. Ongoing clinical trials aim at answering the question whether the addition of daclizumab and basiliximab will allow to avoid or decrease the use of more toxic immunosuppressive drugs.

Antibodies, Monoclonal↗
PubMed1999

Constructing a prediction interval for time to reach a threshold concentration based on a population pharmacokinetic analysis: an application to basiliximab in renal transplantation.

Basiliximab is an immunosuppressant chimeric monoclonal antibody directed to the human interleukin-2 receptor alpha-chain used for prevention of acute rejection episodes in organ transplantation. The minimally effective serum concentration necessary to saturate receptor epitopes in kidney transplant patients is 0.2 microgram/ml. To guide dose selection for Phase 3 efficacy trials, a population pharmacostatistical model was fitted to intensively sampled Phase 2 pharmacokinetic data. This served as a basis from which to examine candidate dose regimens with respect to the duration over which receptor-saturating concentrations would be achieved posttransplant. Three prediction methods were assessed: one based on simulations, and two others based on first-order approximation using either inverse regression or inversion of confidence intervals. An 80% prediction interval was generated by each method to evaluate its predictive performance against prospectively collected Phase 3 data in 39 renal transplant patients who received two injections of 20 mg basiliximab, one prior to surgery and one on Day 4 posttransplant. All methods provided correct prediction of the duration of receptor-saturating concentration. As anticipated, the best performance was obtained from the simulation method which predicted 30 values in the 80% prediction interval, 19.7-52.7 days. The actually observed 80% interval from the Phase 3 data was 23.7-58.3 days.

Algorithms↗
PubMed2000

[Monoclonal interleukin-2 receptor antibodies and their use in clinical kidney transplantation: basiliximab and daclizumab].

Basiliximab and daclizumab are analogous immunosuppressive agents approved for clinical renal transplantation. Both drugs are gene manipulated chimeric human/murine monoclonal antibodies with specificity against the alpha-chain of the interleukin-2 receptor (IL-2R) on activated T lymphocytes. By combining the drugs with calcineurin inhibitor based immunosuppression, an inhibition of the interleukin-2 (IL-2) synthesis as well as the IL-2/IL-2R reception is obtained. Consequently, the allogeneic immune response is suppressed and the risk of acute rejection of the transplant is reduced. By treatment with basiliximab or daclizumab in the recommended doses, a blockade of the IL-2R is obtained for up to 12 weeks. The incidence of acute rejection episodes is reduced by approx. 33%. The incorporation of human amino acid sequences has almost eliminated the immunogenicity of the drugs and reduced their rates of elimination. The side effects of prophylactic treatment with basiliximab/daclizumab do not differ from those of placebo.

Antibodies, Monoclonal↗
PubMed2001

Use of basiliximab and daclizumab in kidney transplantation.

Kidney transplantation represents a major medical victory in patients with whom dialysis and medical therapy have failed. To increase survival rates and optimize the use of limited organs, both patient care and immunosuppression therapy must be improved. Reduction in rejection episodes or severity of rejection may ultimately improve long-term allograft survival. Traditional engineered monoclonal antibodies have been associated with severe cytokine release reactions and an increased risk of opportunistic infections. Basiliximab and daclizumab are chimeric and humanized monoclonal antibodies which inhibit thymus-dependent lymphocyte proliferation. Interleukin-2 also affects the proliferation of natural killer cells, macrophages and monocytes, bursa-equivalent lymphocytes, epidermal dendritic cells, and lymphokine-activated killer cells. Interleukin-2 receptor antagonists have been shown to reduce the incidence of acute rejection without increasing the incidence of opportunistic infections or malignancy. Further studies are needed to evaluate the overall effect of these agents on long-term patient and allograft survival.

Antibodies, Monoclonal↗