Etanercept Biosimilar Comparable to Originator in Biologic-Naïve Patients With RA

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At months 6 and 12, the proportion of patients who were able to achieve DAS28 remission and EULAR response was similar across treatment arms.

Real-world data from a large analysis proved that biologic-naïve patients with rheumatoid arthritis (RA) treated with either etanercept originator or biosimilar showed similar outcomes, including drug survival and disease activity at month 6 and 12, according to a study published in Rheumatology.1

Etanercept, a tumor necrosis factor inhibitor (TNF), has been a main treatment option for patients with RA in the United Kingdom since its approval in the early 2000s. However, biologic therapies often come with high treatment and annual costs. Because of this, biosimilar options of the drug, first introduced in 2016, are now used to treat at least 90% of new patients.2

“Previous observational studies have shown outcomes in over 900 patients with RA defined with stable disease activity switching from etanercept originator to biosimilar,” wrote Lianne Kearsley-Fleet, PhD, epidemiologist at the Centre for Epidemiology Versus Arthritis at the University of Manchester, and colleagues. “However, real-world evidence comparing etanercept originator and etanercept biosimilar is limited.”

The British Society for Rheumatology Biologics Register in Rheumatoid Arthritis (BSRBR-RA) cohort study was used to identify biologic-naïve patients with RA beginning treatment with etanercept. Patients were included between January 2010 and June 2022 and had at least 1 year of available follow-up data. Demographics, such as age and gender, disease duration, and disease activity information were collected at baseline.

Follow-up data of interest included changes in disease activity and anti-rheumatic therapy. Function was determined using the Health Assessment Questionnaire (HAQ). Primary outcomes, collected at month 6 and month 12 included Disease Activity Score for 28 joints (DAS28) remission, minimal clinically important difference (MCID) in HAQ, and the European Alliance of Associations for Rheumatology (EULAR) response (moderate and good vs no response).

Drug survival was determined using Kaplan-Meier and Cox regression, which included reasons for treatment discontinuation. Confounding by indication was accounted for using propensity-decile adjustment.

Of the 1806 biologic-naïve patients with RA identified, 1009 were given the originator and 797 were prescribed the biosimilar. Baseline characteristics were similar among both groups, with 74% female, 94% White, and a median age of 59 years at the beginning of treatment. Median disease duration before etanercept initiation was 5 years and most (60%) were receiving concomitant methotrexate.

At months 6 and 12, the proportion of patients who were able to achieve DAS28 remission and EULAR response was similar across treatment arms. The median improvement of DAS28 from baseline to 6 months was 2.4 units in both cohorts and 2.5 units at 1 year. Remission was achieved by 26% of patients in the originator group and 31% in the biosimilar group at month 6. A good EULAR response was reported in 38% of those in the originator cohort and 45% in the biosimilar cohort at month 6. At the 1-year mark, 35% of patients in both cohorts achieved MCID in HAQ.

During the follow-up period, 19% of patients receiving the originator switched to the biosimilar and were censored at the time of switch. Patients treated with the originator were not more likely to stop therapy when compared with the biosimilar. Most patients remained on therapy at 1 year (71% in the originator cohort and 76% in the biosimilar cohort).

Investigators noted limitations inherent in real-world observational studies. As the originator was available much earlier than the biosimilar, there were less follow-up data in the biosimilar group, which may have possibly led to bias. However, the Cox proportional hazard model adjusted for differences in patient characteristics and censored patients at final follow-up to limit this bias.

“These data are reassuring to both patients and clinical teams when considering starting etanercept originator or biosimilar therapy as their first biologic,” investigators concluded.


  1. Kearsley-Fleet L, Rokad A, Tsoi MF, et al. Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA [published online ahead of print, 2023 Mar 21]. Rheumatology (Oxford). 2023;kead127. doi:10.1093/rheumatology/kead127
  2. Commissioning framework for biological medicines - NHS england. (n.d.). Retrieved April 12, 2023, from