A new Canadian real-world evidence study has demonstrated comparable clinical outcomes between etanercept biosimilars and the originator product in patients with rheumatoid arthritis, adding to the growing body of evidence supporting biosimilar interchangeability. The analysis, published in Arthritis Research & Therapy, found no meaningful differences in remission rates between patients initiating biosimilar etanercept products and those starting the reference drug Enbrel.
Study Design and Patient Population
The multicenter analysis evaluated 150 adults with rheumatoid arthritis from four Canadian prospective cohorts who initiated etanercept therapy between January 2015 and May 2022. All participants were etanercept-naive at baseline, with 65.3% (n=98) receiving biosimilars (Brenzys or Erelzi) and 34.7% (n=52) receiving the originator Enbrel.
The study population was predominantly female (76.0%) and largely White (82.2%), with a mean age of 56.8 years at etanercept initiation. Notably, patients in the biosimilar group were diagnosed at a younger age than those receiving the originator (mean 47.7 vs 54.2 years) and had longer disease duration (9.3 years vs 5.1 years). Most participants (72.7%) initiated therapy after 2017, reflecting the 2016 approval of the first etanercept biosimilar in Canada.
Remission Outcomes Show No Significant Differences
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 compared to 14.5 months (95% CI, 4.7-18.6) for originator users. However, this difference was not statistically significant (log-rank P = 0.51). Multivariate Cox regression analysis confirmed no clear difference in time to first remission between groups (adjusted HR, 1.52; 95% CI, 0.68-3.39).
The probability of achieving first remission within 12 months was 0.63 for biosimilar users and 0.47 for originator users. For sustained remission, defined as at least two consecutive visits in remission within 12 months, rates were similar between groups: 19.5% for biosimilar initiators and 21.0% for originator initiators. Adjusted analyses showed no significant difference (adjusted OR, 1.14; 95% CI, 0.29-4.87).
Interestingly, the only baseline factor associated with increased likelihood of remission was hydroxychloroquine use (adjusted HR, 1.96; 95% CI, 1.01-4.73).
Alignment with Previous Research
These findings mirror results from randomized controlled trials and European registry data, which have consistently demonstrated comparable outcomes between etanercept biosimilars and the originator. A British prospective cohort study found similar proportions of remission at 6 months (31% vs 26%) and 12 months (34% vs 27%) between biosimilars and originator etanercept. Similarly, a Catalonian retrospective study observed that 66.7% of biosimilar users and 54.6% of originator users achieved remission at 52 weeks.
The consistency across different healthcare systems and study designs reinforces the clinical interchangeability of etanercept biosimilars, supporting their use as therapeutic alternatives to the reference product.
Healthcare Economic Implications
The study's findings have significant implications for healthcare economics and patient access. Biosimilars are increasingly important to managed care systems due to their potential to expand access and reduce costs, with estimates suggesting biosimilars could generate $44.2 billion in savings. In Canada, biologics accounted for 27.3% of public drug expenditures in 2018 despite representing less than 2% of claims, highlighting the substantial financial impact of these therapies.
Canadian policymakers have responded by implementing biosimilar adoption initiatives, contributing to the generation of more real-world evidence for these products. This contrasts sharply with the United States, where etanercept biosimilars face delayed market entry due to patent litigation, despite FDA approvals for Erelzi in 2016 and Eticovo in 2019.
Clinical Practice Implications
The study authors concluded that "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."
For clinicians treating rheumatoid arthritis, these results provide reassurance that biosimilar etanercept products can be prescribed with confidence in their clinical effectiveness. The comparable remission rates and time to response support treatment decisions based on factors such as cost, availability, and patient preference rather than concerns about reduced efficacy.
The research adds valuable real-world evidence to support regulatory and clinical guidelines for biosimilar use, particularly in healthcare systems seeking to optimize treatment access while managing costs. As more etanercept biosimilars enter various markets, this evidence base will be crucial for informing treatment decisions and policy development.
