PMID- 27220317
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20181113
IS  - 1573-2592 (Electronic)
IS  - 0271-9142 (Print)
IS  - 0271-9142 (Linking)
VI  - 36
IP  - 6
DP  - 2016 Aug
TI  - Long-Term Tolerability, Safety, and Efficacy of Recombinant Human 
      Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for 
      Primary Immunodeficiency.
PG  - 571-82
LID - 10.1007/s10875-016-0298-x [doi]
AB  - 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.
FAU - Wasserman, Richard L
AU  - Wasserman RL
AD  - Allergy Partners of North Texas Research, Dallas, TX, USA.
FAU - Melamed, Isaac
AU  - Melamed I
AD  - IMMUNOe Clinical Research Center, Centennial, CO, USA.
FAU - Stein, Mark R
AU  - Stein MR
AD  - Allergy Associates of the Palm Beaches, North Palm Beach, FL, USA.
FAU - Engl, Werner
AU  - Engl W
AD  - Baxalta Innovations GmbH, Vienna, Austria.
FAU - Sharkhawy, Marlies
AU  - Sharkhawy M
AD  - Baxalta Innovations GmbH, Vienna, Austria.
FAU - Leibl, Heinz
AU  - Leibl H
AD  - Baxalta Innovations GmbH, Vienna, Austria.
FAU - Puck, Jennifer
AU  - Puck J
AD  - University of California San Francisco, San Francisco, CA, USA.
FAU - Rubinstein, Arye
AU  - Rubinstein A
AD  - Allergy & Immunology Division, Montefiore Medical Center, Bronx, NY, USA.
FAU - Kobrynski, Lisa
AU  - Kobrynski L
AD  - Emory Children's Center, Emory University, Atlanta, GA, USA.
FAU - Gupta, Sudhir
AU  - Gupta S
AD  - University of California, Irvine, CA, USA.
FAU - Grant, Andrew J
AU  - Grant AJ
AD  - University of Texas Medical Branch, Galveston, TX, USA.
FAU - Ratnayake, Anoshie
AU  - Ratnayake A
AD  - West Coast Clinical Trials, Cypress, CA, USA.
FAU - Richmond, Wendell G
AU  - Richmond WG
AD  - Allergy and Asthma Physicians, Hinsdale, IL, USA.
FAU - Church, Joseph
AU  - Church J
AD  - Children's Hospital Los Angeles, Los Angeles, CA, USA.
FAU - Yel, Leman
AU  - Yel L
AD  - Baxalta US Inc., Cambridge, MA, USA.
FAU - Gelmont, David
AU  - Gelmont D
AD  - Baxalta US Inc., Westlake Village, CA, 91362-3811, USA. 
      david.gelmont@baxalta.com.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20160525
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bacterial Infections/drug therapy/etiology
MH  - Child
MH  - Female
MH  - Hospitalization
MH  - Humans
MH  - Hyaluronoglucosaminidase/*administration & dosage/adverse effects
MH  - Immunoglobulins, Intravenous/*administration & dosage/adverse effects
MH  - Immunologic Deficiency Syndromes/*drug therapy
MH  - Infusions, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Recombinant Proteins/*administration & dosage/adverse effects
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4940441
OTO - NOTNLM
OT  - Subcutaneous IgG replacement
OT  - efficacy
OT  - primary immunodeficiency
OT  - recombinant human hyaluronidase
OT  - tolerability
EDAT- 2016/05/26 06:00
MHDA- 2017/12/08 06:00
PMCR- 2016/05/25
CRDT- 2016/05/26 06:00
PHST- 2015/12/15 00:00 [received]
PHST- 2016/05/11 00:00 [accepted]
PHST- 2016/05/26 06:00 [entrez]
PHST- 2016/05/26 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
PHST- 2016/05/25 00:00 [pmc-release]
AID - 10.1007/s10875-016-0298-x [pii]
AID - 298 [pii]
AID - 10.1007/s10875-016-0298-x [doi]
PST - ppublish
SO  - J Clin Immunol. 2016 Aug;36(6):571-82. doi: 10.1007/s10875-016-0298-x. Epub 2016 
      May 25.