title: CD25 blockade in kidney transplant patients randomized to standard-dose or high-dose basiliximab with cyclosporine, or high-dose basiliximab in a calcineurin inhibitor-free regimen.
abstract: An increased basiliximab dose may saturate T-cell CD25 receptors in kidney transplant patients receiving calcineurin inhibitor (CNI)-free immunosuppression. In a 12-week study, 16 de novo kidney transplant patients were randomized to (i) 40 mg basiliximab with cyclosporine [n = 3] (controls), (ii) 80 mg basiliximab with cyclosporine [n = 6], or (iii) 80 mg basiliximab with everolimus (CNI-free) [n = 7], all with mycophenolic acid and steroids. Recruitment was stopped prematurely due to increased biopsy-proven acute rejection (BPAR) in the basiliximab 80 mg CNI-free group. BPAR occurred in 1/3, 1/6, and 4/7 patients in the three treatment groups, respectively. The primary endpoint, area under the effect curve of CD25 saturation to week 12, was 8.4(1.6) % × weeks in the control group, 11.1(1.1) % × weeks with basiliximab 80 mg + cyclosporine, and 9.7(0.7) % × weeks in the basiliximab 80 mg CNI-free group (P = 0.020 for basiliximab 80 mg + cyclosporine versus controls; P = 0.119 for basiliximab 80 mg CNI-free versus controls). Although small patient numbers prohibit robust conclusions, these results suggest that doubling the cumulative basiliximab dose to 80 mg does not provide adequate immunosuppression during the first 3 months after kidney transplantation in the absence of CNI therapy (ClinicalTrials.gov number: NCT01596062).
authors.affiliation: Laboratoire d'Immunologie, Bretonneau Hospital, CHRU de Tours, CNRS, GICC UMR 7292, Université François-Rabelais de Tours, Tours, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Thibault
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Bretonneau Hospital, CHRU de Tours, CNRS, GICC UMR 7292, Université François-Rabelais de Tours, Tours, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.affiliation: Service de Nephrologie-Transplantation, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM U 845, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Department of Nephrology, Transplantation and Dialysis, CHU Bordeaux, Pellegrin Hospital, UMR-CNRS 5164, Bordeaux University, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.affiliation: Laboratoire d'Immunologie, Bretonneau Hospital, CHRU de Tours, CNRS, GICC UMR 7292, Université François-Rabelais de Tours, Tours, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Coulon
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Bretonneau Hospital, CHRU de Tours, CNRS, GICC UMR 7292, Université François-Rabelais de Tours, Tours, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Chasseuil
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Bretonneau Hospital, CHRU de Tours, CNRS, GICC UMR 7292, Université François-Rabelais de Tours, Tours, France.
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.affiliation: Department of Nephrology, Dialysis and Organ Transplantation, Rangueil Hospital, Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: Department of Nephrology, INSERM UMR 1197, Kremlin Bicetre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.affiliation: Novartis Pharma SAS, Rueil-Malmaison, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Di Giambattista
authors.affiliation: Department of Nephrology and Clinical Immunology, Bretonneau Hospital, CHRU de Tours, EA4245, Université François-Rabelais de Tours, Tours, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Büchler
authors.affiliation: Department of Nephrology and Clinical Immunology, Bretonneau Hospital, CHRU de Tours, EA4245, Université François-Rabelais de Tours, Tours, France.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
mesh_terms: D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077552:Basiliximab; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D065095:Calcineurin Inhibitors; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab
keywords: CD25; IL-2; basiliximab; cyclosporine; everolimus; saturation