Drug Survival of Biosimilars, Originator TNF Inhibitors Similar

The discontinuation due to inefficacy or adverse events for biosimilars and originators of the tumor necrosis factor inhibitors etanercept and adalimumab were similar, according to a study analyzing the treatment survival rates of patients in the BIOBADASER cohort. BIOBADASER is a Spanish multicenter prospective registry of patients with rheumatic diseases who are receiving biologics and targeted disease-modifying antirheumatic drugs.

The results were published in The Journal of Rheumatology.¹

The discontinuation due to inefficacy or adverse events for biosimilars and originators of the tumor necrosis factor inhibitors etanercept and adalimumab were similar.

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Etanercept was first approved in Europe in 2016² with adalimumab following in 2017.³ There are now 3 etanercept and 10 adalimumab biosimilars approved in the European Union.⁴ In the US, 2 etanercept biosimilars have been approved but have yet to launch due to legal challenges.⁴ Similar to Europe, there are 10 approved and launched adalimumab biosimilars in the US.

Biosimilars are a recommended treatment where they are available because of the potential for savings, and the European Alliance of Associations for Rheumatology prefers therapies that cost less when efficacy and safety is the same, the authors explained.¹

“However, there are no recommendations regarding the interchangeability or replacement of an originator by biosimilar molecules,” they noted. “Similar efficacy, safety, and immunology data have been consistently reported with different biosimilars compared to their original molecules, although some observational studies have reported lower retention rates for biosimilars after nonmedical switching.”

This study compared drug discontinuations between biosimilars and the reference products for etanercept and adalimumab and analyzed the factors influencing drug survival. A total of 4162 patients were included who had undergone 4723 courses of treatment (2991 of adalimumab and 1732 of etanercept). Of the patients in the study, 16.41% received originator products, 87.22% received biosimilars, 3.6% received both a biosimilar and an originator, and 6.2% were treated with both adalimumab and etanercept.

Patients included started therapy in January 2016 (etanercept) or January 2018 (adalimumab) and had treatment for 3 or more months until October 2023. Nearly half (45.99%) of patients had rheumatoid arthritis and more than half (60.31%) were women. For more than half (62.18%) of the cases, biosimilars were used as first-line treatment and in total they were prescribed in 84.71% of cases.

Patients on biosimilars tended to be older (52.2 vs 48.4 years) with shorter disease duration (8.3 vs 9.3 years) at the start of the therapy. More than a third (36.42%) of treatment courses were discontinued by the end of the study. Treatment with originator products was more frequently discontinued than biosimilars (53.32% vs 33.37%) with the most common reasons being inefficacy (60.35%) and adverse events (17.85%). Only 1.34% on biosimilars and 0.82% on the originators discontinued due to remission. Patients on biosimilars were more likely to discontinue due to nonmedical switching (6.28% vs 3.07%).

The risk of overall discontinuation was lower for biosimilars in the Cox regression model, and the factors that increased the risk of discontinuation were female sex, obesity, second-line treatment, and third or subsequent lines of treatment.

Biosimilars were more often used with concomitant methotrexate, convention synthetic disease-modifying antirheumatic diseases (csDMARDs), and corticosteroids compared with originator products. Concomitant methotrexate was associated with a lower risk of discontinuation, as was disease duration. However, in patients with axial spondyloarthritis, concomitant use of methotrexate was associated with a greater risk of discontinuation.

Corticosteroids were the only drug associated with lower drug survival.

The authors noted that the encouraging environment in Spain may have biased clinicians to support the use of biosimilars. They also acknowledged that residual confounding may exist as they could not include all factors in the models, such as changes in concomitant csDMARDs over time.

The findings suggested that there was no difference in long-term drug survival due to inefficacy or adverse events between the biosimilars and the originators, which "can be reassuring when deciding to start a biosimilar,” the authors concluded.

References

1. Martínez-Vidal MP, Fernández-Carballido C, Otero-Varela L, et al. Long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to originators: results from a multicenter prospective registry. J Rheumatol. 2024;51(9):877-883. doi:10.3899/jrheum.2024-0001

2. Benepali, the first etanercept biosimilar referencing Enbrel, approved in the European Union. Biogen. News release. January 16, 2016. Accessed September 4, 2024. https://investors.biogen.com/news-releases/news-release-details/benepalir-first-etanercept-biosimilar-referencing-enbrelr

3. European Commission approves Amgevita (biosimilar adalimumab) for the treatment of certain inflammatory conditions. Amgen. News release. March 23, 2017. Accessed September 4, 2024. https://www.amgen.com/newsroom/press-releases/2017/03/european-commission-approves-amgevita-biosimilar-adalimumab-for-the-treatment-of-certain-inflammatory-diseases

4. Biosimilar approvals. The Center for Biosimilars®. Updated March 22, 2024. Accessed September 4, 2024. https://www.centerforbiosimilars.com/biosimilar-approvals