Use Of Basiliximab Research Articles

Use of basiliximab with mycophenolate mofetil in kidney transplantation

Introduction Randomized, placebo-controlled studies have determined that administration of basiliximab (chimeric IL-2 receptor antagonist) decreases the acute rejection rate in kidney transplantation when used in combination with cyclosporine, azathioprine, and steroids. We report our experience using basiliximab with mycophenolate mofetil, a calcineurin inhibitor, and steroids in kidney transplantation. Methods We retrospectively analyzed 127 patients who received their first kidney transplant between September 1, 1998, and December 30, 2000, including 59 who received basiliximab (22 living and 37 cadaveric donor recipients) and the 68 that did not receive this antibody (31 living and 37 cadaveric donor recipients). The groups were demographically comparable for risk factors such as race, peak of panel-reactive antibody, delayed graft function, donor age, and cold ischemia time. The analysis assessed serum creatinine levels, acute rejection, cytomegalovirus infection, and posttransplant lymphoproliferative disease incidence as well as patient and graft survival at 6 months. Results Serum creatinine levels were 3 ± 3.1 and 2.6 ± 2.5 mg/dL ( P = .346) at discharge, 1.5 ± 0.6 and 1.7 ± 1.1 mg/dL ( P = .098) at 1 month, and 1.5 ± 0.7 and 1.6 ± 0.7 mg/dL ( P = .454) at 6 months posttransplantation for patients treated with versus without basiliximab, respectively. Only one episode of acute rejection was seen among patients treated with basiliximab within 1 month posttransplantation versus three episodes among patients treated without basiliximab ( P = .382). Three patients (5.1%) treated with basiliximab and two patients (2.9%) treated without basiliximab developed acute rejection within 6 months posttransplantation ( P = .536). Patient and graft survivals at 6 months posttransplantation were not significantly different between patients treated with versus without basiliximab (100% and 100% versus 100% and 98.3%, respectively). There was no increased incidence of cytomegalovirus infection with the use of basiliximab (5.1% vs 5.9%, P = .844). There was only one case of posttransplant lymphoproliferative disease within 6 months posttransplantation in a patient treated without basiliximab. Conclusion These data suggest that the routine addition of basiliximab to a mycophenolate mofetil-based regimens does not appear to be warranted. A larger prospective randomized study with longer follow-up is needed to confirm these results.

A retrospective analysis of 2 years experience using basiliximab (BMAB) in high risk lung transplant recipients(LTR) at a single institution

The use of anti-CD25 monoclonal antibodies, including Basiliximab, in renal and liver transplantation has been shown to reduce the incidence of acute rejection(AR) and increase time to first rejection episode. Benefits of BMAB use in LTR are not yet clear. We used BMAB induction where early initiation of high dose cyclosporine(CyA) may precipitate renal impairment(RI) in the setting of difficult/ prolonged operations, low pre-Tx creatinine clearance and/or in pre-sensitized recipients (eg. high PRA).

Experience with the use of basiliximab in liver transplantation—use in pediatric and adult recipients in combination with cyclosporine or tacrolimus

Experience with the use of basiliximab in liver transplantation—use in pediatric and adult recipients in combination with cyclosporine or tacrolimus

Use of basiliximab in conjunction with either Neora/MMF/steroids or Prograf/MMF/steroids in simultaneous pancreas-kidney transplantation

Use of basiliximab in conjunction with either Neora/MMF/steroids or Prograf/MMF/steroids in simultaneous pancreas-kidney transplantation

Pharmacoeconomic evaluation of simulect prophylaxis in renal transplant recipients

Advances in immunosuppressive therapy have substantially improved one-year clinical outcomes for renal transplantation.1 However, acute rejection still occurs in up to 50% of kidney transplantation recipients during the first year,2 and it remains the major contributor to chronic rejection and long-term graft failure. [3], [4] and [5] Although episodes of acute rejection are reversible with heightened doses of steroids and antibody therapy, the implications for increased healthcare costs and poor long-term outcome underscore the importance of developing therapies to reduce acute rejection. Basiliximab (Simulect, Novartis, Basel, Switzerland) is a high-affinity chimeric antiinterleukin-2 receptor monoclonal antibody that is indicated for the prophylaxis of acute rejection after renal transplantation. [6] and [7] Randomised clinical trials have demonstrated that basiliximab is highly effective in suppressing acute rejection when used in combination with dual therapy of cyclosporin and steroids. [8] and [9] Recently, a phase III international multi-centre trial was performed to evaluate the effectiveness of basiliximab in renal transplantation patients receiving a standard triple therapy regimen of cyclosporin, steroids, and azathioprine.10 An economic evaluation of the trial was undertaken alongside the clinical studies. We determined the economic impact of adding basiliximab to triple therapy. Our objectives were to compare within-trial resource use between basiliximab-treated and placebo-treated patients within six months of renal transplantation and to evaluate the cost implications of basiliximab use, relative to clinical outcomes.

First experience with basiliximab in pediatric liver graft recipients.

Several studies have shown a significant reduction of acute cellular graft rejection in adult liver and kidney graft recipients treated with monoclonal anti-interleukin-2 (IL-2)-receptor antibodies. The mechanism was inhibition of activated T-helper cells by blocking the alpha-chain (CD25) of the IL-2 receptor. The pilot study described here evaluated the use of basiliximab in pediatric liver transplantation (LTx), which is the first report on its use in children. Fifty-two liver-transplanted children were analyzed in this study. A matched-pair historical control group (n = 26) received cyclosporin A (CsA) and prednisolone, and patients in the basiliximab group (n = 26) were treated with low-dose CsA and basiliximab (after reperfusion and on day 4 post-transplant). The incidences were compared of acute graft rejections, infectious complications, and the adverse effects of immunosuppressive medication within the first 6 months post-transplant. The incidence of acute rejection was significantly higher in the control group (61.5% vs. 11.5%, p = 0.0004). The frequency of infectious complications was similar (46.1% vs. 53.8%). Patients in the basiliximab group showed less arterial hypertension; however, the differences were not statistically significant (30.7% vs. 7.7%, p = 0.07). Nephrotoxicity, hepatotoxicity or neurotoxicity were only seen in the control group (7.7%; 3.8%; 3.8%, respectively). Hence, the use of basiliximab in combination with CsA and steroids in pediatric liver transplant recipients is safe and reduces the incidence of acute graft rejection. Further studies are needed to confirm our preliminary results and to analyze long-term effects on post-transplant lymphoproliferative disease, chronic rejection, and patient survival.

Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients

KIDNEY transplantation is the treatment of choice for patients with end-stage renal disease. Acute rejection (AR) episodes are still a major problem in renal transplant recipients (RTR), predisposing them for chronic allograft dysfunction and graft loss. The search for more specific immunosuppressive agents to prolong graft survival has recently led us to focus on anti-interleukin (IL)-2 receptor antibodies (anti-IL-2Rab) in induction therapy. Two anti-IL-2 Rab are now approved for clinical use. They are biologically engineered to contain more human gene regions and fewer murine-derived regions. These are basiliximab (Simulect; Novartis, Basel, Switzerland) and daclizumab (Zenapax; Hoffman-La Roche, Switzerland). Reports of successful clinical trials of these agents in induction treatment of RTR is already available in the literature. These authors found anti IL-2 Rab useful for prevention of AR episodes and reported good tolerability. This paper reports on a prospective study of use of basiliximab (Simulect) and daclizumab (Zenapax) in induction immunosuppression in mismatched first renal transplants in our unit.

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.

ANALYSIS OF REJECTION AND ATN AFTER INDUCTION WITH ATG, BASILIXIMAB AND DACLIZIMAB IN CADAVERIC KIDNEY TRANSPLANT RECIPIENTS

14 Basiliximab (Simulect) and daclizumab (Zenapax) are monoclonal antibody therapies directed against the alpha subunit of the IL-2 receptor. Although basiliximab and daclizumab have similar mechanisms of action, daclizumab requires 5 doses compared to 2 doses of basiliximab. The cost per dose of basiliximab and daclizumab are comparable ($1224 and $1254 respectively). We examined the recent use of basiliximab and daclizumab in our center and compared the results to ATG (ATGAM) induction in cadaveric renal allografts. 106 patients were treated with ATG from 1/92 to 3/98. 69 patients were induced with basiliximab from 12/97 to 12/98. 37 recipients were induced with daclizumab from 7/97 to 7/98. Maintenance immunosuppression consisting of prednisone, mycophenolate mofetil or azathioprine and cyclosporine or FK506 was used in all patients. Demographics such as recipient age, sex and race were comparable in each treatment group. Rejection and ATN rates are depicted below. (Table)TableExamination of early allograft rejection (1 - 2 months post-transplant) showed the highest rate of rejection among those patients treated with daclizumab while similar early rejection rates were seen in those patients treated with basiliximab and ATG. Late allograft rejection rates (3-4 months post-transplant) were not significantly different in patients treated with basiliximab and daclizumab (p=0.65) and higher than ATG recipients. Rates of post-transplant ATN (as defined by the need for hemodialysis post-transplant) were not statistically different between treatment groups. However, when rejection rates in recipients with post-transplant ATN were examined, recipients induced with ATG had less rejection than those treated with either basiliximab or daclizumab (p=0.06). Lack of a statistically significant difference in rejection with ATN could be attributed to the small number in each treatment group. The total cost of treatment with Zenapax ($6270) was greater than that of a course of Simulect ($2448). Given the similar rejection rates for Simulect and Zenapax at 120 days post-transplant, Simulect appears to be the more economic choice. While ATG is more expensive than both Simulect and Zenapax, patients with post-transplant ATN induced with ATG had a lower incidence of rejection.