title: Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.
authors.affiliation: Allergy Partners of North Texas Research, Dallas, TX, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wasserman
authors.affiliation: IMMUNOe Clinical Research Center, Centennial, CO, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Melamed
authors.affiliation: Allergy Associates of the Palm Beaches, North Palm Beach, FL, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Stein
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Engl
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: Marlies
authors.initials: M
authors.lastname: Sharkhawy
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Leibl
authors.affiliation: University of California San Francisco, San Francisco, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Puck
authors.affiliation: Allergy & Immunology Division, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Arye
authors.initials: A
authors.lastname: Rubinstein
authors.affiliation: Emory Children's Center, Emory University, Atlanta, GA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kobrynski
authors.affiliation: University of California, Irvine, CA, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
authors.affiliation: University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grant
authors.affiliation: West Coast Clinical Trials, Cypress, CA, USA.
authors.forename: Anoshie
authors.initials: A
authors.lastname: Ratnayake
authors.affiliation: Allergy and Asthma Physicians, Hinsdale, IL, USA.
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Richmond
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Church
authors.affiliation: Baxalta US Inc., Cambridge, MA, USA.
authors.forename: Leman
authors.initials: L
authors.lastname: Yel
authors.affiliation: Baxalta US Inc., Westlake Village, CA, 91362-3811, USA. david.gelmont@baxalta.com.
authors.forename: David
authors.initials: D
authors.lastname: Gelmont
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D002648:Child; D005260:Female; D006760:Hospitalization; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage* / Q000009:adverse effects; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016756:Immunoglobulins, Intravenous; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase
keywords: Subcutaneous IgG replacement; efficacy; primary immunodeficiency; recombinant human hyaluronidase; tolerability