title: The challenging definition of naïve patient for biological drug use.
abstract: Biosimilar is defined by The European Medical Agency as a biological medicinal product, which is similar but not identical to the biological drug already authorized. The biosimilar and its reference product are expected to display the same safety and efficacy profile and are generally used to treat the same conditions. The Italian Medicines Agency considers biosimilars as a valid therapeutic option with an economic advantage, especially in primary naïve patients with no previous exposure to the originator or with a sufficiently long wash-out period ("secondary naïve"). The identification of "secondary naïve" is not well defined and can be subjected to different variables, mainly the drug biologic effect and its immunogenicity. The first one depends on the type of biologics and on their mechanism of action. The second one is related to the fact that biologicals may be immunogenic and can trigger an anti-drug antibody response (ADA). ADA may behave as neutralizing antibodies blocking the active site of the biological but can also recognize other epitopes favoring the formation of immune-complexes that eventually affect the pharmacodynamics. Moreover, the concomitant immune-suppressive treatment can affect the immunogenicity, even if the exact mechanism remains unknown. In conclusion, the development and use of biosimilars represent a tool for increasing health system sustainability. However it is of paramount importance to distinguish between the pharmacodynamics of a given drug and its immunogenicity being the two aspects unrelated. Thus a detailed definition of "secondary naïve" patients is challenging, and may be related to both the two parameters.
authors: Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Istituto G. Pini, Milan, Italy. Electronic address: martina.biggioggero@gmail.com.
authors: Martina
authors: M
authors: Biggioggero
authors: Department of Internal Medicine, Azienda Ospedaliera di Pavia, Pavia, Italy. Electronic address: marco_danova@ospedali.pavia.it.
authors: Marco
authors: M
authors: Danova
authors: Department of Biomedical Sciences for Health, University of Milan, Division of Legal and Insurance Medicine, Milan, Italy. Electronic address: umberto.genovese@unimi.it.
authors: Umberto
authors: U
authors: Genovese
authors: Department of Nephrology, Alessandro Manzoni Hospital, Lecco, Italy. Electronic address: f.locatelli@ospedale.lecco.it.
authors: Francesco
authors: F
authors: Locatelli
authors: Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Istituto G. Pini, Milan, Italy; Istituto Auxologico Italiano, Milan, Italy. Electronic address: pierluigi.meroni@unimi.it.
authors: Pier Luigi
authors: PL
authors: Meroni
authors: Department of Hematology and Marrow Transplantation, University Federico II of Naples, Naples, Italy. Electronic address: fabrizio.pane@unina.it.
authors: Fabrizio
authors: F
authors: Pane
authors: Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. Electronic address: francesco.scaglione@unimi.it.
authors: Francesco
authors: F
authors: Scaglione
mesh_terms: D001688:Biological Products / Q000627:therapeutic use*; D003429:Cross Reactions; D006801:Humans; D007156:Immunologic Memory
chemical_list: D001688:Biological Products
keywords: Biologicals; Biosimilars; Drug biologic effect; Immunogenicity; Pure red cell aplasia; Secondary naïve patient