title: Evaluating dose ratio of subcutaneous to intravenous immunoglobulin therapy among patients with primary immunodeficiency disease switching to 20% subcutaneous immunoglobulin therapy.
abstract: BACKGROUND
  Current prescribing information recommends that physicians apply a dose ratio of 1.37:1 (1.53:1 prior to January 2015) in the United States (US) when switching patients with primary immunodeficiency disease (PI) from intravenous (IVIG) therapy to most subcutaneous therapy ([SCIG], except the 10% SCIG human hyaluronidase and immune globulin). However, a dose ratio of 1:1 was studied and approved for the European Union (EU). The dose-adjustment ratio used by prescribers in real-world US clinical practice is unknown.
  
  
  OBJECTIVE
  To examine real-world Hizentra 20% SCIG-to-IVIG dose ratios in the US after PI patients are switched from IVIG to 20% SCIG (Hizentra).
  
  
  METHODS
  A retrospective longitudinal study was conducted using prescription shipment data of patients with PI from specialty pharmaceutical and service providers from 2011 to 2016. Patients who had at least 1 shipment of IVIG prior to switching to 20% SCIG (Hizentra) and subsequently received at least 1 more 20% SCIG (Hizentra) shipment in the following 6 months were included. Monthly 20% SCIG (Hizentra) doses following a switch from IVIG were calculated for each 2-month interval by summing daily doses that were estimated by dividing shipped volume by days between shipments. Mean monthly IVIG dose was calculated from the total volume shipped prior to switch. Per-patient dose ratios of Hizentra 20% SCIG-to-IVIG were calculated by dividing monthly 20% SCIG (Hizentra) dose by monthly IVIG dose during each 2-month interval. To minimize the influence of outliers, median dose ratios were reported. Dose ratios at months 2 to 4, 4 to 6, and 6 to 8 were compared with the dose ratio at months 0 to 2 using the Wilcoxon signed rank test. A sensitivity analysis excluding pediatric patients was conducted to assess the impact of changes in weight.
  
  
  RESULTS
  Data from 278 patients who met the inclusion criteria showed that median Hizentra 20% SCIG-to-IVIG dose ratios were 1.14:1 at 0 to 2 months post switch, 1.09:1 at 2 to 4 months, and stabilized at 1.05:1 at 4 to 6 and 6 to 8 months post switch. Median dose ratios at months 2 to 4, 4 to 6, and 6 to 8 were statistically significantly lower than the median dose ratio at 0 to 2 months post switch (all P < .001). Similar results were seen in the sensitivity analysis excluding pediatric patients.
  
  
  CONCLUSIONS
  Real-world data indicate that patients were switched to 20% SCIG (Hizentra) from IVIG at dose ratios lower than recommended by US prescribing information but similar to prescribing information in the EU. The initial dose ratio of 1.14:1 at 0 to 2 months stabilized to 1.05:1 at 4 to 6 and 6 to 8 months, which was consistent with reports of dose-equivalent switching patterns used in management of PI in clinical practice in the US.
authors.affiliation: CSL Behring, 1020 1st Avenue, King of Prussia, PA. E-mail: shanthy.krishnarajah@cslbehring.com.
authors.forename: Girishanthy
authors.initials: G
authors.lastname: Krishnarajah
authors.forename: Jee-Yeon K
authors.initials: JK
authors.lastname: Lehmann
authors.forename: Brian
authors.initials: B
authors.lastname: Ellman
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Bhak
authors.forename: Maral
authors.initials: M
authors.lastname: DerSarkissian
authors.forename: Deane
authors.initials: D
authors.lastname: Leader
authors.forename: Ann L
authors.initials: AL
authors.lastname: Bullinger
authors.forename: Mei
authors.initials: M
authors.lastname: Sheng Duh
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage; D055104:Infusions, Subcutaneous; D007345:Insurance Claim Review / Q000706:statistics & numerical data; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D012189:Retrospective Studies; D014481:United States; D055815:Young Adult
chemical_list: C558471:Hizentra; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors