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

• Published in: Journal of clinical immunology Vol. 36; no. 6; pp. 571 - 582
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2016; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Bacterial Infections - drug therapy; Bacterial Infections - etiology; Biomedical and Life Sciences; Biomedicine; Child; Female; Hospitalization; Humans; Hyaluronoglucosaminidase - administration & dosage; Hyaluronoglucosaminidase - adverse effects; Immunoglobulins, Intravenous - administration & dosage; Immunoglobulins, Intravenous - adverse effects; Immunologic Deficiency Syndromes - drug therapy; Immunology; Infectious Diseases; Infusions, Subcutaneous; Internal Medicine; Male; Medical Microbiology; Middle Aged; Original; Original Article; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Time Factors; Treatment Outcome; Young Adult; recombinant human hyaluronidase; primary immunodeficiency; Subcutaneous IgG replacement; efficacy; tolerability
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-016-0298-x

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.