Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;108(4):734-755.
doi: 10.1002/cpt.1836. Epub 2020 Apr 30.

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review

Liese Barbier  1 , Hans C Ebbers  2 , Paul Declerck  1 , Steven Simoens  1 , Arnold G Vulto  1   3 , Isabelle Huys  1
Affiliations

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review

Liese Barbier et al. Clin Pharmacol Ther. 2020 Oct.

Abstract

To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real-world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open-label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect.

PubMed Disclaimer

Conflict of interest statement

I.H., S.S., P.D., and A.G.V. are the founders of the KU Leuven Fund on Market Analysis of Biologics and Biosimilars following Loss of Exclusivity (MABEL Fund). S.S., I.H., and A.G.V. have conducted biosimilar research sponsored by Hospira (now Pfizer). S.S. was involved in a stakeholder roundtable on biosimilars sponsored by Amgen, Pfizer, and MSD, and has participated in an advisory board meeting for Pfizer. S.S. works with Pfizer to carry out biosimilar research. A.G.V. is involved in consulting, advisory work, and speaking engagements for a number of companies (i.e., AbbVie, Amgen, Biogen, EGA, Pfizer/Hospira, Mundipharma, Roche, and Sandoz). He has no personal benefit from these activities; any compensation is paid to his employer. P.D. participated at advisory board meetings for AbbVie, Amgen Hospira, and Samsung‐Bioepis, and is on the Speakers' Bureau of AbbVie, Celltrion, Hospira, Merck Serono, and Roche. At the time of study initiation and during the major part of the study, H.C.E. was employed at the Dutch Medicines Evaluation Board (MEB). The views expressed in this paper are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the MEB. H.E. is currently employed by Biogen, the Netherlands B.V. L.B. declared no competing interests for this work. All authors declare that the research was conducted in the absence of any commercial or financial relationship that could be perceived as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of number of switch studies across products.
Figure 2
Figure 2
Overview of different switch study designs. B, biosimilar; R, reference product; rand., randomization.
Figure 3
Figure 3
Number of studies with ADA and/or trough level measurements. ADA, antidrug antibody; TL, trough level.
See this image and copyright information in PMC

References

    1. European Medicines Agency . Guideline on similar biological medicinal products. 2014.
    1. European Medicines Agency . Medicines ‐ Centrally authorised biosimilar medicines <https://www.ema.europa.eu/medicines/field_ema_web_categories%253Aname_fi...>. Accessed July 21, 2019.
    1. The US Food and Drug Administration . Biosimilar Product Information ‐ FDA Approved Biosimilar Products <https://www.fda.gov/drugs/biosimilars/biosimilar‐product‐information>. Accessed July 21, 2019.
    1. IMS Institute for Healthcare Informatics . Delivering on the Potential of Biosimilar Medicines: The Role of Functioning Competitive Markets (2016).
    1. van Overbeeke, E. , De Beleyr, B. , de Hoon, J. , Westhovens, R. & Huys, I. Perception of originator biologics and biosimilars: a survey among Belgian rheumatoid arthritis patients and rheumatologists. BioDrugs 31, 447–459 (2017). - PubMed

Publication types