Canadian RWE Shows Comparable Outcomes Between Etanercept Biosimilars, Originator

As the US continues to wait for etanercept biosimilars to be allowed entrance into the market,¹ a new Canadian analysis using real-world evidence (RWE) found no meaningful differences in remission outcomes between individuals with rheumatoid arthritis (RA) initiating etanercept biosimilars and those starting the reference product.²

As the US continues to wait for etanercept biosimilars to be allowed entrance into the market, a new Canadian analysis using real-world evidence (RWE) found no meaningful differences in remission outcomes between patients treated with etanercept biosimilars vs the reference product. | Image credit: ungvar - adobe.stock.com

The study, published in Arthritis Research & Therapy, evaluated 150 adults with RA from 4 Canadian prospective cohorts who initiated etanercept therapy between January 2015 and May 2022. Participants were etanercept naive at baseline, and 65.3% (n = 98) received a biosimilar (Brenzys or Erelzi), while 34.7% (n = 52) received the originator (Enbrel).

The overall cohort was predominantly female (76.0%) and largely White (82.2%). The mean age at etanercept initiation was 56.8 years, with individuals in the biosimilar group diagnosed at a younger age than those in the originator group (mean, 47.7 vs 54.2 years). The mean RA duration was longer among biosimilar initiators (9.3 years vs 5.1 years). Obesity (body mass index ≥ 30) was reported in 41.4% of participants, and 16.0% were current smokers. Most individuals (72.7%) initiated therapy after 2017, reflecting the 2016 approval of the first etanercept biosimilar in Canada.

Among the 125 participants with active disease at baseline, the median time to first remission was 8.7 months (95% CI, 5.2-12.1) for biosimilar users and 14.5 months (95% CI, 4.7-18.6) for originator users. However, the difference was not statistically significant (log-rank P = .51). Multivariate Cox regression showed no clear difference in time to first remission (adjusted HR, 1.52; 95% CI, 0.68-3.39).

Sustained remission, defined as at least 2 consecutive visits in remission within 12 months, was achieved by 19.5% of biosimilar initiators and 21.0% of originator initiators. Adjusted analyses showed no significant difference (adjusted OR, 1.14; 95% CI, 0.29-4.87). The only baseline factor associated with increased likelihood of remission was hydroxychloroquine use (adjusted HR, 1.96; 95% CI, 1.01-4.73).

The findings mirror results from randomized controlled trials and European registry data, which have consistently shown comparable outcomes between etanercept biosimilars and the originator. Observational studies in the UK and Catalonia also reported similar remission rates, reinforcing the clinical interchangeability of biosimilars.

Biosimilars are increasingly important to managed care systems due to their potential to expand access and reduce costs, with some estimates predicting that biosimilars could generate 44.2 billion between.³ In Canada, biologics accounted for 27.3% of public drug expenditures in 2018 despite representing less than 2% of claims.⁴ Policy makers have responded by implementing biosimilar adoption initiatives, contributing to greater RWE for these products.⁵

By contrast, in the US, etanercept biosimilars have faced delayed market entry.¹ Although the FDA approved Erelzi (Sandoz) in 2016 and Eticovo (Samsung Bioepis) in 2019, patent litigation with Amgen has kept them off the US market. Enbrel, first approved in 1998, continues to face limited biosimilar competition, highlighting a key barrier to affordability in the US health care system.

The authors of the present analysis concluded, “Biosimilars present an opportunity to expand treatment options for RA patients while mitigating healthcare costs. Our study contributes to the growing body of evidence supporting the equivalence of biosimilars and bio-originators.”²

Reference
1. Herman B. Amgen wins Enbrel drug paten appeal. Axios. July 2, 2020. Accessed August 25, 2025. https://www.axios.com/2020/07/02/amgen-enbrel-drug-patent-appeal

2. Birck MG, Boivin J, Yan L, et al. Disease remission and sustained remission after etanercept biosimilar or originator initiation in rheumatoid arthritis: an interim real-world analysis. Arthritis Res Ther. 2025;27:150. doi:10.1186/s13075-025-03607-7

3. Joszt L. Biosimilars can create huge savings, but interchangeability needs to be reviewed. AJMC^®. April 10, 2023. Accessed December 17, 2024. www.ajmc.com/view/biosimilars-can-create-huge-savings-but-interchangeability-needs-to-be-reviewed

4. Lexchin J, Law MR. Policies on the use of biosimilars in Canada: developments over the past 5 years. CMAJ. 2022;194(15):E556-E560. doi:10.1503/cmaj.211599

5. Jeremias S. Given public concerns, Canadian policy makers should be cautious when making new biosimilar policies. The Center for Biosimilars^®. May 5, 2022. Accessed August 25, 2025. https://www.centerforbiosimilars.com/view/given-public-concerns-canadian-policy-makers-should-be-cautious-when-making-new-biosimilar-policies