title: Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency.
abstract: BACKGROUND
  Subcutaneous immunoglobulin (IGSC) replacement therapy for primary immunodeficiency (PI) is equally efficacious to intravenous immunoglobulin (IGIV), induces fewer systemic reactions, and may be self-infused. Limited SC infusion volumes and reduced bioavailability, however, necessitate multiple infusion sites, more frequent treatment, and dose adjustment to achieve pharmacokinetic equivalence. Recombinant human hyaluronidase (rHuPH20) increases SC tissue permeability and facilitates dispersion and absorption, enabling administration of monthly doses in one site.
  
  
  OBJECTIVE
  This study investigated the efficacy and tolerability of rHuPH20-facilitated IGSC (IGHy) in patients with PI.
  
  
  METHODS
  In this open-label, multicenter phase III study, 87 patients with PI aged ≥2 years received 10% IGIV for 3 months, then IGHy (n = 83) for approximately 14 to 18 months at 108% of the IGIV dose. IGHy infusions began weekly, increasing to 3- or 4-week intervals.
  
  
  RESULTS
  The majority (94.0%) of IGHy infusions were administered every 3 or 4 weeks, using one site (median, 1.09/month), with a mean volume of 292.2 mL. The bioavailability of IGHy measured by area under the concentration versus time curve was 93.3% of IGIV, which is pharmacokinetically equivalent. Systemic reactions were less frequent with IGHy than with IGIV (8.3% vs 25.0% of infusions). Local reactions to IGHy were generally mild to moderate, with a rate of 0.203 per infusion. The acute serious bacterial infection rate per subject-year for IGHy was low (0.025; upper 99% CI limit, 0.046). Overall infection rates per subject-year were 2.97 for IGHy and 4.51 for IGIV.
  
  
  CONCLUSIONS
  IGHy was effective, safe, and pharmacokinetically equivalent to IGIV at the same administration intervals, but it caused fewer systemic reactions. Tolerability was good despite high infusion volumes and rates.
authors: Allergy/Immunology Research Center of North Texas, Dallas, Tex., USA.
authors: Richard L
authors: RL
authors: Wasserman
authors: Isaac
authors: I
authors: Melamed
authors: Mark R
authors: MR
authors: Stein
authors: Sudhir
authors: S
authors: Gupta
authors: Jennifer
authors: J
authors: Puck
authors: Werner
authors: W
authors: Engl
authors: Heinz
authors: H
authors: Leibl
authors: Barbara
authors: B
authors: McCoy
authors: Victoria G
authors: VG
authors: Empson
authors: David
authors: D
authors: Gelmont
authors: Richard I
authors: RI
authors: Schiff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage*; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000009:adverse effects; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D055104:Infusions, Subcutaneous; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D007136:Immunoglobulins; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase