Efficacy and Safety of a New 10% Intravenous Immunoglobulin Product in Patients with Primary Immune Thrombocytopenia (ITP)

Junshik Hong, Soo-Mee Bang, Yeung-Chul Mun, Ho-Young Yhim, Jaehoon Lee, Hyeong-Seok Lim, Doyeun Oh, Korean GC IVIg Investigators, Junshik Hong, Soo-Mee Bang, Yeung-Chul Mun, Ho-Young Yhim, Jaehoon Lee, Hyeong-Seok Lim, Doyeun Oh, Korean GC IVIg Investigators

Abstract

Background: In the current study, we aimed to investigate the efficacy and safety of intravenous immunoglobulin (IVIg)-SN 10%, a new 10% IVIg formulation, in adult patients with severe primary immune thrombocytopenia (ITP; platelet count < 20 × 109/L).

Methods: Patients diagnosed as primary ITP, aged 19 years old or more, and had a platelet count of < 20 × 109/L by screening complete blood cell count performed within 2 weeks of study commencement were eligible. Patients received IVIg-SN 10% at a dose of 1 g/kg/day for two consecutive days. Response was defined as the achievement of a platelet count of ≥ 50 × 109/L at day 8.

Results: Out of 81 eligible patients, 31 patients were newly diagnosed, 7 patients had persistent ITP, and 43 patients had chronic ITP. In intent-to-treat analysis, 61.3 patients (75.7%) achieved response and satisfied the pre-defined non-inferiority condition. Median time to response was 2 days and mean duration of maintaining response after the completion of IVIg therapy was 9.13 ± 8.40 days. Response rates were not found to be dependent on the phase of ITP or previous treatment for ITP. The drug was well tolerated and the frequency of mucocutaneous bleeding decreased during the study period.

Conclusion: In summary, IVIg-SN 10% formulation was found to be safe and effective in adult ITP patients (Trial registry at ClinicalTrials.gov, NCT02063789).

Keywords: Bleeding; Hemorrhage; IV Immunoglobulins; Immune Thrombocytopenia; Thrombocytopenia.

Conflict of interest statement

Disclosure: The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Diagram of study flow. ITT = intent-to-treat, PK = pharmacokinetic, PP = per-protocol, Ig = immunoglobulin, ITP = immune thrombocytopenia, AE = adverse event.
Fig. 2
Fig. 2
Kaplan-Meier curves for time to response (platelet count of ≥ 50 × 109/L in 7 days) in the ITT set (n = 81). ITT = intent-to-treat.
Fig. 3
Fig. 3
Changes of platelet counts during the study period in the ITT set (n = 81). Platelet count showed continuous increase from the baseline through day 6, then tend to decrease. Among responders, estimated platelet counts were highest at days 6 and 8. ITT = intent-to-treat.

References

    1. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Jr, Crowther MA, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–4207.
    1. Jang JH, Kim JY, Mun YC, Bang SM, Lim YJ, Shin DY, et al. Management of immune thrombocytopenia: Korean experts recommendation in 2017. Blood Res. 2017;52(4):254–263.
    1. Schwartz RS. Immune thrombocytopenic purpura--from agony to agonist. N Engl J Med. 2007;357(22):2299–2301.
    1. Bierling P, Godeau B. Intravenous immunoglobulin for autoimmune thrombocytopenic purpura. Hum Immunol. 2005;66(4):387–394.
    1. Godeau B, Lesage S, Divine M, Wirquin V, Farcet JP, Bierling P. Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin. Blood. 1993;82(5):1415–1421.
    1. Robak T, Salama A, Kovaleva L, Vyhovska Y, Davies SV, Mazzucconi MG, et al. Efficacy and safety of Privigen, a novel liquid intravenous immunoglobulin formulation, in adolescent and adult patients with chronic immune thrombocytopenic purpura. Hematology. 2009;14(4):227–236.
    1. Robak T, Mainau C, Pyringer B, Chojnowski K, Warzocha K, Dmoszynska A, et al. Efficacy and safety of a new intravenous immunoglobulin 10% formulation (octagam® 10%) in patients with immune thrombocytopenia. Hematology. 2010;15(5):351–359.
    1. Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang. 2010;98(1):12–28.
    1. Bjøro K, Frøland SS, Yun Z, Samdal HH, Haaland T. Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. N Engl J Med. 1994;331(24):1607–1611.
    1. Rachid R, Bonilla FA. The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature. J Allergy Clin Immunol. 2012;129(3):628–634.
    1. Etscheid M, Breitner-Ruddock S, Gross S, Hunfeld A, Seitz R, Dodt J. Identification of kallikrein and FXIa as impurities in therapeutic immunoglobulins: implications for the safety and control of intravenous blood products. Vox Sang. 2012;102(1):40–46.
    1. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–2393.
    1. Page LK, Psaila B, Provan D, Michael Hamilton J, Jenkins JM, Elish AS, et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. Br J Haematol. 2007;138(2):245–248.
    1. Bussel JB, Eldor A, Kelton JG, Varon D, Brenner B, Gillis S, et al. IGIV-C, a novel intravenous immunoglobulin: evaluation of safety, efficacy, mechanisms of action, and impact on quality of life. Thromb Haemost. 2004;91(4):771–778.
    1. van der Meer JW, van Beem RT, Robak T, Deptala A, Strengers PF. Efficacy and safety of a nanofiltered liquid intravenous immunoglobulin product in patients with primary immunodeficiency and idiopathic thrombocytopenic purpura. Vox Sang. 2011;101(2):138–146.
    1. Dash CH, Gillanders KR, Stratford Bobbitt ME, Gascoigne EW, Leach SJ. Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (--NCT00504075) PLoS One. 2014;9(6):e96600.
    1. Varga G, Volková Z, Leibl H, Gasztonyi Z, Mayer J, Chojnowski K, et al. Efficacy and safety of the new intravenous immunoglobulin IGIV 10% in adults with chronic idiopathic thrombocytopenic purpura. Transfus Med Hemother. 2006;33(6):509–514.
    1. Julia A, Kovaleva L, Loria S, Alberca I, Hernandez F, Sandoval V, et al. Clinical efficacy and safety of Flebogammadif, a new high-purity human intravenous immunoglobulin, in adult patients with chronic idiopathic thrombocytopenic purpura. Transfus Med. 2009;19(5):260–268.
    1. Wolf HH, Davies SV, Borte M, Caulier MT, Williams PE, Bernuth HV, et al. Efficacy, tolerability, safety and pharmacokinetics of a nanofiltered intravenous immunoglobulin: studies in patients with immune thrombocytopenic purpura and primary immunodeficiencies. Vox Sang. 2003;84(1):45–53.
    1. Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP) Blood. 2005;106(7):2244–2251.
    1. Stasi R, Stipa E, Masi M, Cecconi M, Scimo MT, Oliva F, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995;98(5):436–442.
    1. Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013;121(14):2596–2606.
    1. Kim HS, Lee DH, Lee BK, Cho YS. Prognostic performance evaluation of the International Society on Thrombosis and Hemostasis and the Korean Society on Thrombosis and Hemostasis scores in the early phase of trauma. J Korean Med Sci. 2018;33(3):e21.
    1. Gabrielsson J, Weiner D. Non-compartmental analysis. Methods Mol Biol. 2012;929:377–389.
    1. Feng L. Epidemiological study of selective IgA deficiency among 6 nationalities in China. Zhonghua Yi Xue Za Zhi (Taipei) 1992;72(2):88–90.
    1. Kanoh T, Mizumoto T, Yasuda N, Koya M, Ohno Y, Uchino H, et al. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang. 1986;50(2):81–86.
    1. Rhim JW, Kim KH, Kim DS, Kim BS, Kim JS, Kim CH, et al. Prevalence of primary immunodeficiency in Korea. J Korean Med Sci. 2012;27(7):788–793.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren