No Association Observed Between Biosimilar Rituximab Exposure and Hypersensitivity Hospitalization

According to findings from a 2-cohort study recently published in BioDrugs, exposure to biosimilar rituximab at initiation, switch, or over time was not associated with hospitalization due to hypersensitivity, compared to originator rituximab. 

Originator rituximab is a monoclonal antibody that targets the CD20 protein on B lymphocytes and is used to treat various disorders including, but not limited to, non-Hodgkin lymphoma, chronic lymphoid leukemia, and rheumatoid arthritis. In 2017, biosimilar rituximab entered the market, which lowered the cost of treatment and provided an effective and safe option to rituximab-naive patients. However, pharmacovigilance centers then provided documentation of cases of severe hypersensitivity among patients who were treated with biosimilar rituximab. 

According to the study authors, “the risk of hypersensitivity reaction has been proven to be highest at first rituximab injection. In addition, switch from originator to biosimilar product may lead to an excess risk of hypersensitivity reaction, potentially due to pre-sensitization to originator product and development of antidrug antibodies.” 

To expand the current research on hypersensitivity, Hugo Jourdain, MD, French National Agency for Medicines and Health Products Safety and French National Health Insurance, Saint-Denis, France, and coauthors aimed to assess the association between biosimilar versus originator rituximab and hypersensitivity reactions in a real-world setting. They wished to assess this association among initiators and switchers, as well as at first injection and over time. 

All 91,894 patients who had received rituximab between 2017 and 2021 were identified using data from the French National Health Data System, enrolled as the study population, and divided into 2 cohorts. The initiation cohort consisted of patients who initiated originator rituximab (n=17,605) or biosimilar rituximab (n=74,281). The switch cohort consisted of 17,123 patients who had switched from originator to biosimilar rituximab, who were called “switchers,” and were matched to 24,659 “non-switchers.” Data was collected on these patients’ hospitalizations for events of anaphylactic shock or serum sickness following a rituximab injection. 

Results indicated that at initiation, 49% of patients who were treated with initiator rituximab (n=86) experienced events, versus 46% (n=339) of patients who were treated with biosimilar rituximab. The adjusted odds ratio of biosimilar exposure associated with these events was 1.04, and the adjusted hazard ratio for biosimilar versus originator exposure was 1.15, demonstrating no increased risk of an event with biosimilar use at first injection and over time. Additionally, there was no association found between a switch to biosimilar rituximab and the occurrence of a hypersensitivity event leading to hospitalization. 

As endpoints were met, Dr Jourdain et al concluded that their study results “are reassuring regarding the use of rituximab biosimilars, in the context of fast scale-up and political incentives to prescribe biosimilar products.” They added, “Further real-world studies may still also be carried out with other biosimilar products and studying other product-specific adverse effects to confirm that biosimilar initiation or originator to biosimilar switching does not lead to an increase in signals.”

Source: 

Jourdain, H., Hoisnard, L., Sbidian, E. et al. Severe hypersensitivity reactions at biosimilar versus originator rituximab treatment initiation, switch and over time: A cohort study on the French national health data system. BioDrugs. 2023.  https://doi.org/10.1007/s40259-023-00584-8