title: Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study.
abstract: Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs.
  
  
  
  This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy.
  
  
  
  A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (ΔHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl), responders (0<ΔHb≤2 g/dl), and highly responders (ΔHb>2 g/dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID.
  
  
  
  Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15-20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment.
  
  
  
  No difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment.
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Ingrasciotta
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgianni
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Marcianò
authors.affiliation: Treviso Local Health Unit, Treviso, Italy.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bolcato
authors.affiliation: Treviso Local Health Unit, Treviso, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pirolo
authors.affiliation: Treviso Local Health Unit, Treviso, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Chinellato
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ientile
authors.affiliation: Department of Clinical and Experimental Medicine, AOU Policlinico "G. Martino", University of Messina, Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Santoro
authors.affiliation: Department of Pharmaceutical Sciences, ''A. Avogadro'' University, Novara, Italy.
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.affiliation: Department of Economic Sciences, University of Messina, Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Alibrandi
authors.affiliation: Unit of Biostatistics, IRCCS ''Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.|Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.affiliation: Unit of Clinical Pharmacology, A.O.U. Policlinico ''G. Martino", Messina, Italy.|Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.|Department of Medical Informatics, Erasmus Medical Center, Rotterdam, Netherlands.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Trifirò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007558:Italy; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D010330:Patents as Topic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D059451:Biosimilar Pharmaceuticals; D006397:Hematinics; D006454:Hemoglobins