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Cited by 52Immunodeficiency and Autoimmune DisordersMonoclonal and Polyclonal Antibodies ResearchIntramuscular injections and effects

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

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Wasserman, Richard L., Melamed, Isaac, Stein, Mark R., Engl, Werner, Sharkhawy, Marlies, Leibl, Heinz, Puck, Jennifer, Rubinstein, Arye +8 more·2016·Journal of Clinical Immunology
DOI 10.1007/s10875-016-0298-xPMC PMC4940441
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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 <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.

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  • In a recent study in patients with PI, rHuPH20-facilitated immunoglobulin (IGHy) administered subcutaneously was largely preferred over SCIG without pre-injection of hyaluronidase.

    “In a recent study in patients with PI, rHuPH20-facilitated immunoglobulin (IGHy) administered subcutaneously was largely preferred over SCIG without pre-injection of hyaluronidase.”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [66]

  • Of the 69 patients who completed a satisfaction survey, 65.9% of those who received IVIG then SCIG before IGHy and 75.0% of those who received IVIG before IGHy preferred IGHy.

    “Of the 69 patients who completed a satisfaction survey at the finish of immunoglobulin treatment, 28 received IVIG then SCIG before receiving IGHy, and 41 received IVIG before receiving IGHy; 65.9 and 75.0%, respectively, preferred the IGHy [66].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [66]

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Authors
Wasserman, R. L., Melamed, I., Stein, M. R., Engl, W., Sharkhawy, M., Leibl, H., Puck, J., Rubinstein, A., Kobrynski, L., Gupta, S., Grant, A. J., Ratnayake, A., Richmond, W. G., Church, J., Yel, L., & Gelmont, D.
Affiliations
  • IMMUNOe Research Center (US)
  • Allergy Associates of the Palm Beaches (US)
  • University of California, San Francisco (US)
  • Montefiore Medical Center (US)
  • Emory University (US)
  • University of California, Irvine (US)
  • The University of Texas Medical Branch at Galveston (US)
  • Children's Hospital Los Angeles (US)
  • Baxalta (United States) (US)
Corresponding author
Gelmont, David
ORCID
Venue
Journal of Clinical Immunology
Publisher
Springer Science and Business Media LLC
Published
2016-05-25
Volume
36
Issue
6
Pages
571-582
ISSN
  • 0271-9142 (ISSN-L)
  • 1573-2592
DOI
10.1007/s10875-016-0298-x
PMC
PMC4940441
OpenAlex
W2395452441
Cited by
52
References
38
Citations by year
2026: 4 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 1
FWCI
3.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
Baxalta US Inc.
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
Keywords
recombinant human hyaluronidase, rHuPH20, subcutaneous immunoglobulin, primary immunodeficiency, IgG replacement therapy, long-term safety, adverse events, anti-drug antibodies, infection rate, pediatric and adult patients
MeSH terms
Adolescent, Adult, Aged, Bacterial Infections, Child, Female, Hospitalization, Humans, Hyaluronoglucosaminidase, Immunologic Deficiency Syndromes, Male, Middle Aged, Recombinant Proteins, Time Factors, Immunoglobulins, Intravenous, Treatment Outcome, Infusions, Subcutaneous, Young Adult

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