Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Abstract

Acute graft rejection remains a major problem among additional sequelae in liver transplant recipients. Basiliximab, a chimeric monoclonal antibody with high affinity for the CD25 chain of the interleukin-2 receptor, has significantly reduced the incidence of acute rejection episodes in renal transplant recipients. This single-arm, open-label, multicenter study investigated the efficacy and tolerability of basiliximab immunoprophylaxis in adult patients undergoing first elective liver transplantation. One hundred one patients (70 hepatitis C virus [HCV]-negative patients, 31 HCV-positive patients) were administered basiliximab, 20 mg, by intravenous bolus injection the day of transplantation (day 0) and day 4. In addition, all patients were administered triple immunosuppressive therapy with cyclosporine, steroids, and azathioprine. The efficacy of basiliximab was assessed by conventional parameters, and tolerability was assessed by the incidence of adverse events, infections, and laboratory test result abnormalities. At 6 months, the incidence of first acute biopsy-confirmed rejection episodes was 22.8%. Rejections were more frequent in the HCV-positive (29.0%) than HCV-negative subgroup (20.0%; P ‫؍‬ .441). No rejection episode was graded histologically as severe, and no patient required antibody therapy for the management of acute rejection. Ten patients (9.9%) required treatment with tacrolimus for acute rejection episodes. Patient and graft survival rates at 12 months were 90.1% and 88.1%, respectively. Basiliximab caused no injection-site reactions, anaphylaxis, or cytokine release syndrome. Five malignancies were reported at 12 months: of these, three malignancies predated transplantation surgery. Compared with earlier studies, the addition of basiliximab immunoprophylaxis to triple immunosuppressive therapy provides increased efficacy in reducing the incidence of acute rejection episodes, with no clinically significant increase in adverse events. (Liver Transpl 2002;8: 123-131.)

Fortschritte in der Immunsuppression

“…Hintergrund sind das Nebenwirkungsprofil sowie der postulierte negative Effekt auf den Verlauf der HCV-Infektion. Die Induktionstherapie mit Anti-CD25-Antikörpern hat zur schnelleren Reduktion von Steroiden beigetragen und Rejektionsraten nicht erhöht, sondern sogar zu geringeren steroidrefraktären Rejektionsraten geführt [9,14,15,35]. Auch mit Kaninchen-Anti-Thymozytenglobulin (ATG) und Tacrolimus versus Tacrolimus, Mycophenolsäure und Steroiden konnte ein vergleichbares Über-leben, aber geringere Rejektionsraten der steroidfreien Gruppe gezeigt werden, wobei sogar die HCV-Rekurrenz geringer in der ATG-Gruppe erschien [13,15].…”

Pros and cons of using interleukin-2 receptor antibodies in liver transplant recipients

“…Calmus et al 4 report excellent 1-year patient and graft survival rates of 90.1% and 88.1%, respectively, as well as no anaphylactic reaction or other major side effect related to the infusion of basiliximab. These investigators conclude that the addition of basiliximab resulted in a reduction in the number of rejection episodes compared with a historic control population, with no increased incidence of malignancies, infections, or other side effects.…”

“…Calmus et al 4 report the results of a single-arm, open-label, multicenter trial of basiliximab in which 101 patients were administered basiliximab in conjunction with cyclosporine, azathioprine, and corticosteroids. They found an overall rejection rate of 22.8% at 6 months, with more rejection episodes in patients with hepatitis C (9 of 31 patients; 29.0%).…”

Antibody immunosuppressive therapy in solid-organ transplant

“…In 2002, several studies demonstrated that two-dose basiliximab induction in liver transplant patients was well-tolerated and effective in reducing BPAR rates (35.1% basiliximab vs. 43.5% placebo at sixmonth follow up), although to a lesser extent in HCV-positive cohorts. [103][104][105] Lin et al further demonstrated that by allowing for delayed tacrolimus administration, basiliximab induction preserved renal function better than conventional therapy (renal insufficiency incidence of 26% vs. 67% at three-month follow up). 106 To minimize toxicity, steroid-withdrawal protocols have been actively tested in conjunction with basiliximab usage.…”