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Review: No Safety, Efficacy Issues Found in Patients Who Switched From Originators to Biosimilars


No safety or immunogenicity differences were found in patients who switched to a biosimilar and those who continued on a reference biologic or biosimilar.

Doctor talking to patient | Image credit: Chinnapong - stock.adobe.com

Image credit: Chinnapong - stock.adobe.com

No difference was found in the safety profiles or immunogenicity rates in patients who were switched and those who stayed on a reference biologic or biosimilar, according to the first systematic review using statistical methods to address switching risk in patients between reference biologics and biosimilars in PLoS One.

Biosimilars are progressively available for the treatment of multiple severe disorders, but some concerns remain about switching a patient to a biosimilar whose condition is stable on the reference biologic.

Researchers analyzed the occurrence of safety events after a switch to or from a biosimilar and its reference biologic in all identified controlled clinical studies that encompassed a biosimilar approved by the FDA.

Growing the availability and use of biosimilars is an important public health strategy for decreasing drug costs and increasing the accessibility of biological products to underserved populations.

Randomized controlled studies and extension studies with a switch treatment period (STP) to or from a biosimilar and its reference biologic were distinguished from publicly available information sustained by the FDA. These findings were strengthened with data from peer reviewed publications that held information not captured in FDA reviews. A total of 44 STPs were recognized from 31 distinctive studies for 21 different biosimilars.

PRISMA guidelines to extract and synthesize the data were followed. Meta-analysis was undertaken to estimate the overall risk difference across studies. Patients who were switched to or from a biosimilar and its reference biologic make up a cohort of 5,252 patients.

Additionally, deaths, serious adverse events, and treatment discontinuation included in safety data illustrated an overall risk difference of -0.00, 0.00, -0.00 across STPs, respectively. Similar incidence of antidrug antibodies and neutralizing antibodies in patients within a STP who were switched to or from a biosimilar to its reference biologic and patients who were not switched were displayed by immunogenicity data. Also, immune-related adverse events like anaphylaxis, hypersensitivity reactions, and injection site reactions were similar in switched and non-switched patients.

Antidrug antibodies and neutralizing bodies showed comparable incidence between No Switch and Switch arms. The study participants in the STPs are symbolic of patients who would be switched to or from a biosimilar and its reference product and mirror actual use. This outcome is constant with empiric evidence and descriptive reviews of switching biosimilars and referencing biologics.

“The findings in this report raise several timely questions regarding the data needed to support approval of biosimilars and how to address regulatory requirements unique to the [Biologics Price Competition and Innovation Act] for the 'interchangeable' designation,” said the researchers.

Interchangeability designations allow for pharmacists to substitute a reference product for a biosimilar without needing to obtain permission from a provider. It's intended to increase access to biosimilars and shorten wait times for patients to get their prescriptions. However, many experts question whether designations like this should be needed.

Also, the findings supported efforts to decrease the regulatory burden of switching studies as the default approach for acknowledging the switching standard for the interchangeable designation.

This study also supports the reassessment of the need for switches included in clinical studies for candidate biosimilars since an approved biosimilar will be analytically highly similar to its reference product. As familiarity and the support for biosimilar approvals grows, the amount and types of clinical data consistently performed as part of biosimilar development may be decreased, which would also decrease the time and cost of development.

Some limitations were present in this review, including the small number of patients in the safety evaluations from some source material. There were fewer patients in some STPs, but these differences in STP sample size had been taken into consideration in the meta-analysis.

This study acknowledges one of the concerns of the medical community about the safety of switching between reference products and corresponding biosimilar products.

“Data driven materials such as those contained in this report will facilitate efforts to streamline biosimilar development and achieve the full promise of biosimilars,” concluded the researchers.


Herndon TM, Ausin C, Brahme NN, et al. Safety outcomes when switching between biosimilars and reference biologics: a systematic review and meta-analysis. PLoS One. Published online October 3, 2023. doi:10.1371/journal.pone.0292231

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