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

Richard L. Wasserman, Isaac Melamed, Mark R. Stein, Werner Engl, Marlies Sharkhawy, Heinz Leibl, Jennifer Puck, Arye Rubinstein, Lisa Kobrynski, Sudhir Gupta, Andrew J. Grant, Anoshie Ratnayake, Wendell G. Richmond, Joseph Church, Leman Yel, David Gelmont

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalJournal of Clinical Immunology
Volume36
Issue number6
DOIs
StatePublished - Aug 1 2016

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Subcutaneous Infusions
Hyaluronoglucosaminidase
Immunoglobulins
Immunoglobulin G
Safety
Architectural Accessibility
Injections
Subcutaneous Tissue
Infection
Permeability
Appointments and Schedules
Antibodies
Therapeutics

Keywords

  • efficacy
  • primary immunodeficiency
  • recombinant human hyaluronidase
  • Subcutaneous IgG replacement
  • tolerability

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. / Wasserman, Richard L.; Melamed, Isaac; Stein, Mark R.; Engl, Werner; Sharkhawy, Marlies; Leibl, Heinz; Puck, Jennifer; Rubinstein, Arye; Kobrynski, Lisa; Gupta, Sudhir; Grant, Andrew J.; Ratnayake, Anoshie; Richmond, Wendell G.; Church, Joseph; Yel, Leman; Gelmont, David.

In: Journal of Clinical Immunology, Vol. 36, No. 6, 01.08.2016, p. 571-582.

Research output: Contribution to journalArticle

Wasserman, RL, Melamed, I, Stein, MR, Engl, W, Sharkhawy, M, Leibl, H, Puck, J, Rubinstein, A, Kobrynski, L, Gupta, S, Grant, AJ, Ratnayake, A, Richmond, WG, Church, J, Yel, L & Gelmont, D 2016, 'Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency', Journal of Clinical Immunology, vol. 36, no. 6, pp. 571-582. https://doi.org/10.1007/s10875-016-0298-x
Wasserman, Richard L. ; Melamed, Isaac ; Stein, Mark R. ; Engl, Werner ; Sharkhawy, Marlies ; Leibl, Heinz ; Puck, Jennifer ; Rubinstein, Arye ; Kobrynski, Lisa ; Gupta, Sudhir ; Grant, Andrew J. ; Ratnayake, Anoshie ; Richmond, Wendell G. ; Church, Joseph ; Yel, Leman ; Gelmont, David. / Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. In: Journal of Clinical Immunology. 2016 ; Vol. 36, No. 6. pp. 571-582.
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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",
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AU - Melamed, Isaac

AU - Stein, Mark R.

AU - Engl, Werner

AU - Sharkhawy, Marlies

AU - Leibl, Heinz

AU - Puck, Jennifer

AU - Rubinstein, Arye

AU - Kobrynski, Lisa

AU - Gupta, Sudhir

AU - Grant, Andrew J.

AU - Ratnayake, Anoshie

AU - Richmond, Wendell G.

AU - Church, Joseph

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AU - Gelmont, David

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N2 - 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

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KW - tolerability

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