title: Safety profile of biological medicines as compared with non-biologicals: an analysis of the italian spontaneous reporting system database.
abstract: BACKGROUND
  Biologicals are important treatment options for various chronic diseases. After the introduction of the first biosimilars, animated debate arose in the scientific community about the actual benefit-risk profile of these drugs. In this context, a comparative safety evaluation of biologicals and biosimilars in clinical practice is warranted.
  
  
  METHODS
  We identified all suspected adverse drug reactions (ADRs) concerning biological/biosimilars (excluding vaccines, toxins, blood derivatives, and radio-pharmaceuticals), and further classified them into mechanistic classes. We described the frequency of biological/biosimilar class- and compound-specific ADRs by system organ class (SOC) and type of reporter. We also separately explored the traceability of biologicals and biosimilar-related ADR reports.
  
  
  RESULTS
  Overall 171,201 ADR reports were collected during the observation period; 9,601 (5.6 %) of these concerned biologicals. Biological-related reports were mainly issued by hospital-based physicians (78.7 %). Most of these reports involved monoclonal antibodies and fusion proteins (66.3 %). Reported ADRs were mainly 'skin and subcutaneous tissue disorders' (21 %), 'general and administration site disorders' (17 %), and 'gastrointestinal disorders' (13.6 %). In terms of traceability, 94.8 % of biological-related reports included an identifiable product name, whilst only 8.6 % indicated the corresponding batch number. Regarding biosimilars, 298 reports were identified, with a low proportion indicating drug ineffectiveness (10.1 %).
  
  
  CONCLUSIONS
  Most ADRs attributed to biologicals are 'skin and subcutaneous tissue disorders'. Anticancer monoclonal antibodies are most frequently associated with ADRs. A low proportion of ADR reports concern biosimilars.
authors.affiliation: Department of Clinical and Experimental Medicine, Unit of Clinical Pharmacology, University of Messina, Torre Biologica, Policlinico Universitario, Via Consolare Valeria, Gazzi, 98125, Messina, Italy, pmcutroneo@unime.it.
authors.forename: Paola M
authors.initials: PM
authors.lastname: Cutroneo
authors.forename: Valentina
authors.initials: V
authors.lastname: Isgrò
authors.forename: Alessandra
authors.initials: A
authors.lastname: Russo
authors.forename: Valentina
authors.initials: V
authors.lastname: Ientile
authors.forename: Laura
authors.initials: L
authors.lastname: Sottosanti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pimpinella
authors.forename: Anita
authors.initials: A
authors.lastname: Conforti
authors.forename: Ugo
authors.initials: U
authors.lastname: Moretti
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Trifirò
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects*; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D018570:Risk Assessment
chemical_list: D059451:Biosimilar Pharmaceuticals