title: Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.
abstract: OBJECTIVE
  Intravenous IgG (IVIG) treatment wear-off is commonly experienced by patients, who report increased susceptibility to infection, and decreased quality of life towards the end of their 3- or 4-week dosing cycle, when serum IgG levels approach their trough. We quantified IVIG wear-off in terms of treatment efficacy and patient well-being.
  
  
  METHODS
  Data were collected from patients enrolled in three Phase III trials of Sandoglobulin NF Liquid or Privigen, treated every 3- or 4- weeks. Pooled analyses of raw patient data compared the rate of infection and other clinical outcomes during the course of the dosing cycle. Subjective symptoms of wear-off were quantified by comparing patient-reported overall well-being scores.
  
  
  RESULTS
  The probability of a first infection in the final week of the IVIG cycle was 1.26 (95% confidence intervals [CI]: 0.76-2.11; p = 0.3621) and 1.55 (95% CI: 1.04-2.32; p = 0.0314) times higher than in the first week, for patients on a 3-week cycle and 4-week dosing cycles, respectively. Wear-off, as manifested by a decrease in overall well-being, was experienced in 10% of all cycles and reported at least once by 61% of the patients on a 3-week cycle, and 43% of those on a 4-week cycle.
  
  
  CONCLUSIONS
  These findings confirm the existence of decreased efficacy (treatment wear-off) towards the end of a 3-4 week IVIG dosing cycle, and provide a quantifiable evaluation to a phenomenon typically reported anecdotally. For patients experiencing wear-off, increasing the IgG dose or shortening the dosing interval and/or a switch to SCIG may be beneficial.
authors.affiliation: Clinical Research and Development, CSL Behring LLC, King of Prussia, PA, USA. Mikhail.Rojavin@cslbehring.com.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Rojavin
authors.affiliation: Medical Affairs, CSL Behring AG, Berne, Switzerland.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Hubsch
authors.affiliation: Clinical Research and Development, CSL Behring GmbH, Marburg, Germany.
authors.forename: John-Philip
authors.initials: JP
authors.lastname: Lawo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000097:blood / Q000627:therapeutic use*; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous
keywords: Immunoglobulin replacement therapy; end-dose effect; ivig; primary immunodeficiency; scig; wear-off; well-being