title: Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy.
abstract: To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.
  
  
  
  Population-based observational cohort study.
  
  
  
  All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014.
  
  
  
  Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively.
  
  
  
  ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period.
  
  
  
  Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression.
  
  
  
  We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting.
  
  
  
  In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Belleudi
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fusco
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Amato
authors.affiliation: Drug Policy Area, General Directorate for Health, The Lazio Region, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mecozzi
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Drug Policy Area, General Directorate for Health, The Lazio Region, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sansone
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Davoli
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Addis
mesh_terms: D000740:Anemia / Q000188:drug therapy*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D002318:Cardiovascular Diseases / Q000209:etiology; D002423:Cause of Death; D000068817:Epoetin Alfa / Q000009:adverse effects / Q000627:therapeutic use*; D004920:Erythropoiesis; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy*; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D059451:Biosimilar Pharmaceuticals; D006397:Hematinics; D000068817:Epoetin Alfa
keywords: Comparative effectiveness; biosimilar; cohort study; erythropoiesis-stimulating agents; real life data