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Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol 2012 Oct;130(4):951-7.e11

Date

08/01/2012

Pubmed ID

22846381

DOI

10.1016/j.jaci.2012.06.021

Scopus ID

2-s2.0-84869122138   102 Citations

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 a?Y2 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.

CONCLUSION: 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.

Author List

Wasserman RL, Melamed I, Stein MR, Gupta S, Puck J, Engl W, Leibl H, McCoy B, Empson VG, Gelmont D, Schiff RI, IGSC, 10% with rHuPH20 Study Group



MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Child
Child, Preschool
Humans
Hyaluronoglucosaminidase
Immunoglobulins
Immunologic Deficiency Syndromes
Infusions, Subcutaneous
Middle Aged
Prospective Studies
Recombinant Proteins