Safety profile of biological medicines as compared with non-biologicals: an analysis of the italian spontaneous reporting system database

Drug Saf. 2014 Nov;37(11):961-70. doi: 10.1007/s40264-014-0224-1.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems*
  • Biosimilar Pharmaceuticals / adverse effects*
  • Databases, Factual*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Humans
  • Italy / epidemiology
  • Risk Assessment


  • Biosimilar Pharmaceuticals