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Safety Profile of Biological Medicines as Compared with Non-Biologicals: An Analysis of the Italian Spontaneous Reporting System Database

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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.

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Funding

The study was conducted in the context of the project “Assessment of short and long term risk-benefit profile of biologics through healthcare database network in Italy”, code: RF-2010-2320172, which was funded by the Italian Health Ministry.

Conflict of interest

Professor Achille P. Caputi has received consulting fees that are not related to the content of this study from the following pharmaceutical companies: Bristol-Myers-Squibb, Otsuka, Novartis, Teva and Novo Nordisk. Paola M. Cutroneo, Valentina Isgrò, Alessandra Russo, Valentina Ientile, Laura Sottosanti, Giuseppe Pimpinella, Anita Conforti, Ugo Moretti, and Gianluca Trifirò have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Unit of Clinical Pharmacology, University of Messina, Torre Biologica, Policlinico Universitario, Via Consolare Valeria, Gazzi, 98125, Messina, Italy

    Paola M. Cutroneo, Valentina Isgrò, Alessandra Russo, Valentina Ientile, Achille P. Caputi & Gianluca Trifirò

  2. Italian Medicines Agency, Rome, Italy

    Laura Sottosanti & Giuseppe Pimpinella

  3. Department of Public Health and Community Medicine, University of Verona, Verona, Italy

    Anita Conforti & Ugo Moretti

Authors
  1. Paola M. Cutroneo
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  2. Valentina Isgrò
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  3. Alessandra Russo
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  4. Valentina Ientile
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  5. Laura Sottosanti
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  6. Giuseppe Pimpinella
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  7. Anita Conforti
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  8. Ugo Moretti
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  9. Achille P. Caputi
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  10. Gianluca Trifirò
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Corresponding author

Correspondence to Paola M. Cutroneo.

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Cutroneo, P.M., Isgrò, V., Russo, A. et al. Safety Profile of Biological Medicines as Compared with Non-Biologicals: An Analysis of the Italian Spontaneous Reporting System Database. Drug Saf 37, 961–970 (2014). https://doi.org/10.1007/s40264-014-0224-1

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  • DOI: https://doi.org/10.1007/s40264-014-0224-1

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