Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary ImmunodeficiencyReport as inadecuate




Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency - Download this document for free, or read online. Document in PDF available to download.

Journal Title:

Journal of Clinical Immunology

Volume:

Volume 36, Number 6

Publisher:

Springer Verlag Germany | 2016-08-01, Pages 571-582

Type of Work:

Article | Final Publisher PDF

Abstract: Purpose: Treatment of primary immunodeficiency diseases PIDD with subcutaneous SC infusions of IgG preceded by injection of recombinant human hyaluronidase rHuPH20 IGHy to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies. Methods: Subjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous IV dose, facilitated by prior injection of 75 U-g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased ramped-up to a 3- or 4-week schedule. Results: Eighty-three subjects 24 < 18 years; 59 ≥ 18 years received 2729 infusions excluding ramp-up at a mean dose of 0.155 g-kg-week in the pivotal and 0.156 g-kg-week in the extension study. IGHy exposure exceeded 30 months in 48 subjects. During 187.7 subject-years of IGHy exposure, 2005 adverse events AEs 10.68 per subject-year occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68-subject-year in months 1–12 to approximately 1.50-subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160. The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years. Conclusions: Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.

Subjects: Health Sciences, Immunology - Health Sciences, Pathology - Research Funding: This clinical investigation was sponsored by Baxalta US Inc., Westlake Village, CA.

Keywords: Science and Technology - Life Sciences and Biomedicine - Immunology - Subcutaneous IgG replacement - recombinant human hyaluronidase - primary immunodeficiency - efficacy - tolerability - QUALITY-OF-LIFE - IGG SELF-INFUSIONS - ANTIBODY DEFICIENCIES - REPLACEMENT THERAPY - GAMMA-GLOBULIN - HOME TREATMENT - DISEASES - CHILDREN - LIQUID -



Author: Richard L. Wasserman, Isaac Melamed, Mark R. Stein, Werner Engl, Marlies Sharkhawy, Heinz Leibl, Jennifer Puck, Arye Rubinstein,

Source: https://open.library.emory.edu/



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