No Differences in Treatment Persistence, Safety Detected for Anti-TNF Biosimilars vs Originators

A real-world study using data from the French National Health Data System, which covers 99% of the French population, found no significant differences in treatment persistence or safety between anti-tumor necrosis factor (TNF)-α biosimilars and reference products in all indications of these biologics.

TNF-α plays an important role in immune-mediated inflammatory diseases by inducing transcription factor activity and signaling pathways that lead to, for example, immune cell activation and release of pro-inflammatory cytokines. Monoclonal antibodies targeting TNF, including etanercept, infliximab, and adalimumab are expensive but they “have significantly improved the therapeutic care of immune-mediated inflammatory diseases,” the authors said. However, biosimilars have lowered the cost of treatment. In Europe, there are 4 approved infliximab biosimilars starting in 2015, 12 adalimumab biosimilars starting in 2018, and 4 etanercept biosimilars starting in 2016 have been approved and are on the market in Europe.

Data from the French National Health Data System was used to identify patients initiating therapy with infliximab, adalimumab, and etanercept between 2015 and 2021. Patients were followed for 1 year after initiation, and persistence and safety were compared between those treated with reference products and biosimilars. There were 86,776 patients included in the study, 22,670 treated with infliximab, 24,442 treated with etanercept, and 39,664 treated with adalimumab. About half of patients (49,752; 53%) initiated treatment with biosimilars. The investigators reported that baseline patient characteristics were similar between originator and biosimilar users within each molecule.

Risk of Discontinuation Either Similar or Lower in Biosimilar Groups

For patients receiving infliximab, 39% of patients on the biosimilar discontinued treatment, compared to 38% on the reference product. For etanercept, 46% of patients on the biosimilar discontinued treatment, compared to 52% on the reference product. For adalimumab, 43% of patients in both biosimilar and reference product groups discontinued treatment. In their analysis, the authors found no significant differences in the risk of discontinuation between biosimilar and reference product groups overall.

In some subgroups, however, the risk of discontinuation was lower in patients receiving biosimilar treatment: infliximab treatment in Crohn disease (adjusted HR [aHR]; 0.83; 95% CI, 0.71-0.96), mainly in patients using CT-P13; etanercept treatment in rheumatoid arthritis (aHR, 0.85; 95% CI, 0.78-0.93), ankylosing spondylitis (aHR, 0.88; 95% CI, 0.80-0.96), and psoriasis (aHR, 0.80; 95% CI, 0.65-1.00); and adalimumab treatment of ankylosing spondylitis (aHR, 0.89; 95% CI, 0.81-0.97).

No Significant Differences in Adverse Event Rates

The investigators reported, “across molecules, adverse event rates were mostly similar.” The most frequently observed adverse events were severe infection, all-cause hospitalization, and death. There were no significant differences between biosimilar- and originator-treated patients within each molecule.

The authors concluded their study showed no differences in persistence and safety in real-world use of anti-TNF biosimilars compared to their reference products in all licensed indications. To their knowledge, this is the largest real-world cohort of infliximab, etanercept, and adalimumab biosimilar and originator users, and the first to be assessed for persistence and safety. They added that their results suggest anti-TNF biosimilars can be “used more broadly in order to limit the financial impact of these molecules on health systems.”

Reference

Jourdain H, Hoisnard L, Sbidian E, Zureik M. Persistence and safety of anti-TNF biosimilars versus originators in immune-mediated inflammatory diseases: an observational study on the French National Health Data System. RMD Open. 2024;10(1):e003531. doi:10.1136/rmdopen-2023-003531