Subscribe to RSS
Download PDF
DOI: 10.1160/TH03-10-0650
IGIV-C, a novel intravenous immunoglobulin: evaluation of safety, efficacy, mechanisms of action, and impact on quality of life
Financial support: This work was supported by Bayer HealthCare as part of the clinical development of Gamunex.
Publication History
Received
26 October 2003
Accepted after revision
02 January 2004
Publication Date:
06 December 2017 (online)
Summary
The general safety and efficacy of intravenous immunoglobulin (IGIV) as treatment for idiopathic thrombocytopenic purpura (ITP) has been well-studied. The current study compares the safety and efficacy of a novel IGIV (IGIV-C; Gamunex®, 10%) with a licensed solvent/detergent-treated product (IGIV-S/D; Gamimune®N, 10%) in treatment of ITP. Ninety-seven pediatric and adult patients with acute and chronic ITP were treated in a multi-center, prospective, randomized, double-blind parallel group, non-inferiority trial at 26 international sites. Baseline data (age, duration of ITP, platelet counts, previous treatment) were comparable between groups. Patients were treated with 1 g/kg/day of IGIV-C or IGIV-S/D for 2 days. The primary endpoint, proportion of patients whose platelet counts increased from ≤20 × 109/L to ≥50 × 109/L within 7 days after dosing, was achieved by 35/39 (90%) and 35/42 (83%) of patients treated with IGIV-C and IGIV-S/D, respectively. A secondary endpoint, maintaining platelet counts ≥50 × 109/L for ≥7 days, was achieved by 29/39 (74%) of IGIV-C and 25/42 (60%) IGIV-S/D treated patients. Compared with IGIV-S/D, fewer patients treated with IGIV-C received corticosteroids beyond day 7 (p = 0.02). Efficacy was independent of the presence of isoantibodies or blood type, supporting mechanisms of effect different from anti-D treatments. Adverse events were generally mild and occurred with similar frequency in each group. Viral safety monitoring for HIV, HCV, HBV and Parvovirus B19 showed no seroconversions on study. In conclusion, IGIV-C is as safe and efficacious as IGIV-S/D in treatment of ITP.
† Dr. Shmuel Gillis was tragically killed in a terrorist attack on his way home from Hadassah Hospital on February 1, 2001. Professor Amiram Eldor was tragically killed in a plane crash on November 24, 2001. This manuscript is dedicated in their names
-
References
- 1 George JN, Woolf SH, Raskob GE. et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88: 3-40.
- 2 Cines D, Blanchette V. Immune thrombocytopenic purpura. N Engl J Med 2002; 346: 995-1008.
- 3 Portielje JE, Westendorp RG, Kluin-Nelemans HC. et al. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97: 2549-54.
- 4 Cooper N, Woloski BM, Fodero EM. et al. Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid splenectomy?. Blood 2002; 99: 1922-7.
- 5 Souid AK, Sadowitz PD. Acute childhood immune thrombocytopenic purpura. Diagnosis and treatment. Clinical Pediatrics (Philadelphia) 1995; 34: 487-94.
- 6 Woerner SJ, Abildgaard CF, French BN. Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura. Pediatrics 1981; 67: 453-60.
- 7 Imbach P, Barandun S, d’Apuzzo V. et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1981; 01: 1228-31.
- 8 Bussel JB, Kimberly RP, Inman RD. et al. Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura. Blood 1983; 62: 480-6.
- 9 Bussel JB, Pham LC. Intravenous treatment with gammaglobulin in adults with immune thrombocytopenic purpura: review of the literature. Vox Sang 1987; 52: 206-11.
- 10 Carroll RR, Noyes WD, Rosse WF. et al. Intravenous immunoglobulin administration in the treatment of severe chronic immune thrombocytopenic purpura. Am J Med 1984; 76: 181-6.
- 11 Oral A, Nusbacher J, Hill JB. et al. Intravenous gamma globulin in the treatment of chronic idiopathic thrombocytopenic purpura in adults. Am J Med 1984; 76: 187-92.
- 12 Warrier I, Lusher JM. Intravenous gamma globulin treatment for chronic idiopathic thrombocytopenic purpura in children. Am J Med 1984; 76: 193-8.
- 13 Bussel JB, Schulman I, Hilgartner MW. et al. Intravenous use of gammaglobulin in the treatment of chronic immune thrombocytopenic purpura as a means to defer splenectomy. J Pediatr 1983; 103: 651-4.
- 14 Kurlander R, Coleman RE, Moore J. et al. Comparison of the efficacy of a two-day and a five-day schedule for infusing intravenous gamma globulin in the treatment of immune thrombocytopenic purpura in adults. Am J Med 1987; 83: 17-24.
- 15 Blanchette V, Imbach P, Andrew M. et al. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet 1994; 344: 703-7.
- 16 Colovic M, Dimitrijevic M, Sonnenburg C. et al. Clinical efficacy and safety of a novel intravenous immunoglobulin preparation in adult chronic ITP. Hematol J 2003; 04: 358-62.
- 17 Godeau B, Lesage S, Divine M. et al. Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated highdose intravenous immunoglobulin. Blood 1993; 82: 1415-21.
- 18 Korneyeva M, Hotta J, Lebing W. et al. Enveloped virus inactivation by caprylate: a robust alternative to solvent-detergent treatment in plasma derived intermediates. Biologicals 2002; 30: 153-62.
- 19 Lebing W, Remington K, Schreiner C. et al. Properties of a new intravenous immunoglobulin (IVIG-C, 10%) produced by caprylate virus inactivation and column chromatography. Vox Sang 2003; 84: 193-201.
- 20 Trejo SR, Hotta J, Lebing W. et al. Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process. Vox Sang 2003; 84: 176-87.
- 21 Ballow M, Berger M, Bonilla FA. et al. Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (GamunexTM, 10%). Vox Sang 2003; 84: 202-10.
- 22 Blanchette VS, Luke B, Andrew M. et al. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in child-hood acute immune thrombocytopenic purpura. J Pediatr 1993; 123: 989-95.
- 23 Imbach P, Wagner HP, Berchtold W. et al. Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet 1985; 02: 464-8.
- 24 Salama A, Mueller-Eckhardt C, Kiefel V. Effect of intravenous immunoglobulin in immune thrombocytopenia. Lancet 1983; 02: 193-5.
- 25 Bussel JB, Graziano JN, Kimberly RP. et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood 1991; 77: 1884-93.
- 26 George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1994; 331: 1207-11.
- 27 Godeau B, Caulier MT, Decuypere L. et al. Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 0.5 and 1 g/kg b.w. Br J Haematol 1999; 107: 716-9.