title: Efficacy and safety data of subsequent entry biologics pertinent to nephrology practice: a systematic review.
abstract: BACKGROUND
  Subsequent entry biologics (SEBs) may soon be a reality in Canadian nephrology practice. Understanding the worldwide experience with these agents will be valuable to Canadian clinicians.
  
  
  OBJECTIVE
  To compare the efficacy and safety data between SEBs used in nephrology practice and their reference biologic.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Ovid MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, Cochrane Central Register of Controlled Trials.
  
  
  METHODS
  Adult patients with chronic kidney disease (CKD).
  
  
  METHODS
  Our systematic review follows the process outlined by Cochrane Reviews. For efficacy data, all randomized controlled trials (RCTs), quasi-RCTs and observational trials in nephrology practice were included. For safety data, case series, case reports, review articles in nephrology practice and pharmacovigilance programs were included as well.
  
  
  RESULTS
  Only epoetin SEBs trials were published in the literature. Ten studies involving three different epoetin SEBs (epoetin zeta, HX575 and epoetin theta) were included. The mean epoetin dose used did not differ significantly between the SEBs and the reference product. For epoetin zeta and epoetin theta, the mean hemoglobin levels achieved in the studies were similar between the SEBs and the reference epoetin. The HX 575 studies reported a mean absolute change in hemoglobin within the predefined equivalence margin, when compared with the reference biologic. In terms of safety data, 2 cases of pure-red-cell aplasia were linked to the subcutaneous administration of HX 575. Otherwise, the rate of adverse drug reactions was similar when epoetin SEBs were compared with the reference biologic.
  
  
  CONCLUSIONS
  Our analysis is limited by the paucity of information available on SEB use in nephrology with the exception of epoetin SEBs. Methodological flaw was found in one of the epoetin zeta studies which accounted for 45% of pooled results.
  
  
  CONCLUSIONS
  Little clinical difference was found between epoetin SEBs and the reference product. Although not deemed clinically important, the financial implication of a possible dose difference between epoetin zeta and reference product should be considered in pharmacoeconomic studies. Ongoing trials are expected to address the risk of pure-red-cell aplasia with HX 575.
authors.affiliation: St. Paul's Hospital, Providence Healthcare, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6 Canada.
authors.forename: Judith Genevieve
authors.initials: JG
authors.lastname: Marin
authors.affiliation: St. Paul's Hospital, Providence Healthcare, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6 Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Leung
authors.affiliation: British Columbia Provincial Renal Agency, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6 Canada.
authors.forename: Clifford
authors.initials: C
authors.lastname: Lo
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Nicole W
authors.initials: NW
authors.lastname: Tsao
authors.affiliation: British Columbia Provincial Renal Agency, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6 Canada ; Royal Jubilee Hospital, Island Health Authority, 1952 Bay Street, Victoria, British Columbia V8R 1 J8 Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Martinusen
keywords: Darbepoetin; Epoetin alpha; Epoetin beta; Epoetin theta; Epoetin zeta; HX 575; Rituximab; Subsequent entry biologic; Tissue plasminogen activator