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.Objectives: To compare the efficacy and safety data between SEBs used in nephrology practice and their referencebiologic. Design: Systematic review.Sources of information: Ovid MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstractsof Review of Effects, Cochrane Central Register of Controlled Trials.Patients: Adult patients with chronic kidney disease (CKD).Methods: Our systematic review follows the process outlined by Cochrane Reviews. For efficacy data, allrandomized controlled trials (RCTs), quasi-RCTs and observational trials in nephrology practice were included. Forsafety data, case series, case reports, review articles in nephrology practice and pharmacovigilance programs wereincluded 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 significantlybetween the SEBs and the reference product. For epoetin zeta and epoetin theta, the mean hemoglobin levelsachieved in the studies were similar between the SEBs and the reference epoetin. The HX 575 studies reported amean absolute change in hemoglobin within the predefined equivalence margin, when compared with thereference biologic. In terms of safety data, 2 cases of pure-red-cell aplasia were linked to the subcutaneousadministration of HX 575. Otherwise, the rate of adverse drug reactions was similar when epoetin SEBs werecompared with the reference biologic.Limitations: Our analysis is limited by the paucity of information available on SEB use in nephrology with theexception of epoetin SEBs. Methodological flaw was found in one of the epoetin zeta studies which accounted for45% of pooled results. Conclusions: Little clinical difference was found between epoetin SEBs and the reference product. Although notdeemed clinically important, the financial implication of a possible dose difference between epoetin zeta andreference product should be considered in pharmacoeconomic studies. Ongoing trials are expected to address therisk of pure-red-cell aplasia with HX 575.