Exposure-Effect Population Model of Inolimomab, a Monoclonal Antibody Administered in First-Line Treatment for Acute Graft-Versus-Host Disease

详细信息    查看全文

• 作者：Céline Dartois (1) (2)
  Gilles Freyer (1) (2) (3)
  Mauricette Michallet (4)
  Emilie Hénin (1) (2)
  Beno?t You (1) (2) (3)
  Isabelle Darlavoix (5)
  Claudine Vermot-Desroches (5)
  Brigitte Tranchand (1) (2) (6)
  Dr Pascal Girard (1) (2)
  
• 刊名：Clinical Pharmacokinetics
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：46
• 期：5
• 页码：417-432
• 全文大小：329KB
• 参考文献：1. Storb R. Allogeneic hematopoietic stem cell transplantation -yesterday, today, and tomorrow. Exp Hematol 2003 Jan; 31(1): 1-0 CrossRef
  2. Ferrara JL, Deeg HJ. Graft-versus-host disease. N Engl J Med 1991 Mar 7; 324(10): 667-4 CrossRef
  3. Storb R, Pepe M, Deeg HJ, et al. Long-term follow-up of a controlled trial comparing a combination of methotrexate plus cyclosporine with cyclosporine alone for prophylaxis of graftversus-host disease in patients administered HLA-identical marrow grafts for leukemia. Blood 1992 Jul 15; 80(2): 560-
  4. Keever CA, Small TN, Flomenberg N, et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood 1989 Apr; 73(5): 1340-0
  5. Ruutu T, Niederwieser D, Gratwohl A, et al. A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow, Transplantation (EBMT). Chronic Leukaemia Working Party of the EBMT. Bone Marrow Transplant 1997 Apr; 19(8): 759-4 CrossRef
  6. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood 1991 Apr 15; 77(8): 1821-
  7. Weisdorf D, Haake R, Blazar B, et al. Treatment of moderate/ severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990 Feb 15; 75(4): 1024-0
  8. Ross WA. Treatment of gastrointestinal acute graft-versus-host disease. Curr Treat Options Gastroenterol 2005 Jun; 8(3): 249-8 CrossRef
  9. Akpek G, Lee SM, Anders V, et al. A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease. Biol Blood Marrow Transplant 2001; 7(9): 495-02 CrossRef
  10. Mollee P, Morton AJ, Irving I, et al. Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis. Br J Haematol 2001 Apr; 113(1): 217-3 CrossRef
  11. Curtis RE, Travis LB, Rowlings PA, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 1999 Oct 1; 94(7): 2208-6
  12. Micallef IN, Chhanabhai M, Gascoyne RD, et al. Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience. Bone Marrow Transplant 1998 Nov; 22(10): 981- CrossRef
  13. Hertenstein B, Stefanic M, Sandherr M, et al. Treatment of steroid-resistant acute graft-vs-host disease after allogeneic marrow transplantation with anti-interleukin-2 receptor antibody (BT563). Transplant Proc 1994 Dec; 26(6): 3114-
  14. Herbelin C, Stephan JL, Donadieu J, et al. Treatment of steroidresistant acute graft-versus-host disease with an anti-IL-2-receptor monoclonal antibody (BT 563) in children who received T cell-depleted, partially matched, related bone marrow transplants. Bone Marrow Transplant 1994 May; 13(5): 563-
  15. Cuthbert RJ, Phillips GL, Barnett MJ, et al. Anti-interleukin-2 receptor monoclonal antibody (BT 563) in the treatment of severe acute GVHD refractory to systemic corticosteroid therapy. Bone Marrow Transplant 1992 Nov; 10(5): 451-
  16. Herve P, Bordigoni P, Cahn JY, et al. Use of monoclonal antibodies / in vivo as a therapeutic strategy for acute GvHD in matched and mismatched bone marrow transplantation. Transplant Proc 1991 Feb; 23 (1 Pt 2): 1692-
  17. Herve P, Wijdenes J, Bergerat JP, et al. Treatment of corticosteroid resistant acute graft-versus-host disease by / in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10). Blood 1990 Feb 15; 75(4): 1017-3
  18. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974 Oct; 18(4): 295-04 CrossRef
  19. Thomas ED, Storb R, Clift RA, et al. Bone-marrow transplantation (second of two parts). N Engl J Med 1975 Apr 24; 292(17): 895-02 CrossRef
  20. Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997 Jun; 97(4): 855-4 CrossRef
  21. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod CM, editor. Evaluation of chemotherapeutic agents. New York: Columbia University Press, 1949: 199-05
  22. Boeckmann AJ, Sheiner L, Beal SL. NONMEM Project Group. NONMEM user’s guides. San Francisco (CA): University of California, 1998
  23. Ette EI, Ludden TM. Population pharmacokinetic modeling: the importance of informative graphics. Pharm Res 1995 Dec; 12(12): 1845-5 CrossRef
  24. Center for Drug Evaluation and Research, Food and Drug Administration, US Department of Health and Human Services. Guidance for industry: population pharmacokinetics [online]. Rockville (MD): Center for Drug Evaluation and Research, 1999. Available from URL: http://www.fda.gov/cder/guidance/1852fnl.pdf [Accessed 2007 Mar 12]
  25. Wade JR, Edholm M, Salmonson T. A guide for reporting the results of population pharmacokinetic analyses: a Swedish perspective. AAPS PharmSci 2005 Oct; 7(2): 45
  26. Agresti A. Modelling ordered categorical data: recent advances and future challenges. Stat Med 1999 Sep 15; 18(17-8): 2191-07 CrossRef
  27. Duffull SB, Chabaud S, Nony P, et al. A pharmacokinetic simulation model for ivabradine in healthy volunteers. Eur J Pharm Sci 2000; 10(4): 285-4 CrossRef
  28. Yano Y, Beal SL, Sheiner LB. Evaluating pharmacokinetic/ pharmacodynamic models using the posterior predictive check. J Pharmacokinet Pharmacodyn 2001 Apr; 28(2): 171-2 CrossRef
  29. Rubin DB. Bayesianly justifiable and relevant frequency calculations for the applied statistician. Ann Stat 1984; 12: 1151-2 CrossRef
  30. Shiiki T, Hashimoto Y, Inui K. Simulation for population pharmacodynamic analysis of dose-ranging trials: usefulness of the mixture model analysis for detecting nonresponders. Pharm Res 2002 Jun; 19(6): 909-3 CrossRef
  31. Cahn JY, Bordigoni P, Tiberghien P, et al. Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody: a multicenter phase III study. Transplantation 1995 Nov 15; 60(9): 939-2 CrossRef
  32. Bay JO, Dhedin N, Goerner M, et al. Inolimomab in steroidefractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: retrospective analysis and comparison with other interleukin-2 receptor antibodies. Transplantation 2005 Sep 27; 80(6): 782- CrossRef
  33. Martin P, Bleyzac N, Souillet G, et al. Relationship between CsA trough blood concentration and severity of acute graftversus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors. Bone Marrow Transplant 2003 Oct; 32(8): 777-4 CrossRef
  34. Andersson BS, Thall PF, Madden T, et al. Busulfan systemic exposure relative to regimen-related toxicity and acute graftversus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biol Blood Marrow Transplant 2002; 8(9): 477-5 CrossRef
  35. Jacobson P, Rogosheske J, Barker JN, et al. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther 2005 Nov; 78(5): 486-00 CrossRef
  36. Beal SL, Sheiner LB, NONMEM Project Group. NONMEM user’s guide: part VII. Conditional estimation methods. San Francisco (CA): University of California, 1998
  37. Frey N, Laveille C, Paraire M, et al. Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation. Br J Clin Pharmacol 2003 Feb; 55(2): 147-7 CrossRef
  38. Zingmark PH, Ekblom M, Odergren T, et al. Population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients. Br J Clin Pharmacol 2003 Aug; 56(2): 173-3 CrossRef
  39. Karlsson MO, Molnar V, Bergh J, et al. A general model for time-dissociated pharmacokinetic-pharmacodynamic relationship exemplified by paclitaxel myelosuppression. Clin Pharmacol Ther 1998 Jan; 63(1): 11-5 CrossRef
  
• 作者单位：Céline Dartois (1) (2)
  Gilles Freyer (1) (2) (3)
  Mauricette Michallet (4)
  Emilie Hénin (1) (2)
  Beno?t You (1) (2) (3)
  Isabelle Darlavoix (5)
  Claudine Vermot-Desroches (5)
  Brigitte Tranchand (1) (2) (6)
  Dr Pascal Girard (1) (2)
  
  1. EA3738 CTO, Faculté de Médecine Lyon Sud, UniversitéLyon 1, Oullins, France
  2. Université de Lyon, Lyon, France
  3. Service d’Oncologie Médicale, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
  4. Service d’Hématologie, H?pital Edouard Herriot, Lyon, France
  5. OPi SA, Limonest, France
  6. Centre Anticancéreux Léon Bérard, Lyon, France
  
• ISSN：1179-1926

文摘

Background and objective Inolimomab, a monoclonal antibody against interleukin (IL)-2Rα (CD25) has shown promising results in the treatment of corticosteroid-resistant acute graft-versus-host disease (GvHD). The objective of the present study was to characterise the pharmacokinetic and pharmacodynamic properties of inolimomab as first-line treatment in this condition. Methods The data came from 21 patients with acute GvHD (8 with an International Bone Marrow Transplant Registry [IBMTR] score of B, 11 with a score of C and 2 with a score of D) following haematopoietic stem cell transplantation after a median delay of 26 days (range 10-27 days). Inolimomab was administered at 0.1, 0.2, 0.3 or 0.4 mg/kg daily in association with methylprednisolone (2 mg/kg) for 8 or 16 days depending on the status at day 9. Then, for responder patients, administrations were continued three times weekly until day 28. Inolimomab concentrations and pharmacodynamic data (acute GvHD scores) were recorded during the study. The pharmacodynamic data were assessed in four grades according to the IBMTR and Glucksberg classification in parallel with Karnofsky scores. A population analysis was developed using a nonlinear mixedeffects model to define the pharmacokinetic model, to test covariates and, when apparent, to model the exposure-effect relationship by a proportional odds model. The modelling was finally qualified by a predictive check. Results The best pharmacokinetic model was two-compartmental. For each score, the most demonstrative exposure-effect graphics linked the cumulative area under the concentration-time curve to cumulated probabilities of observing a specific score. This relationship was identified as a maximum effect model for the skin (with two patient subpopulations: sensitive/less sensitive) and a linear model for the intestinal tract and liver. No covariate was identified as influencing any of these parameters. Conclusion Inolimomab exposure-effect relationships as first-line treatment for acute GvHD have been identified and modelled. The discovered dose-effect relationship allows confirmation of the treatment response, thereby establishing the first step towards optimising the inolimomab dosage in future trials.