Etanercept, Adalimumab Biosimilars Demonstrate Similar Safety Profile to Originators

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Results showed no differences regarding safety, although the biosimilar group had slightly more discontinuations due to inefficacy.

Real-life data extracted from a multicenter cohort of patients with rheumatic diseases revealed a similar safety profile between etanercept and adalimumab biosimilars (SB4 and ABP501, respectively) and their bio-originators, according to research published in Reumatismo.1 Despite a slightly reduced biosimilar retention rate at the 24-month mark, the results show biosimilars are safe and cost-effective alternatives to originators.

Previous research has demonstrated biological disease-modifying antirheumatic drugs (bDMARDs), like adalimumab and etanercept, have an approximate 60 — 70% long-term clinical response rate. Biosimilar options offer an expansion of treatment options and access while maintaining highly similar safety, efficacy, and purity. In Italy, a variety of biosimilar options for etanercept and adalimumab, such as SB4, SB5, ABP501, and GP2015, have been approved in recent years.2

“Since their marketing, numerous real-life studies have been carried out deriving from the data of their use in daily clinical practice: the acceptance rates of the new drug and the retention rate have not always been shown to be equivalent,” wrote Andrea Picchianti-Diamanti, MD, assistant professor of rheumatology at Sapienza University of Rome AOU Sant'Andrea, and colleagues. “A possible hypothesis regarding this difference is the nocebo effect (the negative counterpart of the placebo effect) and the attribution effects (attributing pre-existing or unrelated symptoms to the new treatment); consequently, there is no conclusive evidence.”

A cohort of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with either the reference product or the biosimilar were recruited from prescribing centers in the Lazio region of Italy between 2017 and 2020. Data were collected at baseline and after 4, 8, 12, and 24 months of treatment.

A total of 455 patients treated with biosimilars, of which 276 received SB4 and 179 received ABP501, and 436 patients treated with the originators were included in the analysis. Results showed no differences regarding safety, although the biosimilar group had slightly more discontinuations due to inefficacy (P <.001). Among the predictive factors of reduced drug survival were female gender (P = .05), smoking status (P = .046), and being bDMARD-naïve (P = .001).

At 24 months, the retention rate was 81.1% for patients in the bio-originators group and 76.5% in the biosimilars group (median retention time: 20.7 and 18.9 months, respectively; P = .002). Patients in the biosimilars group who exhibited remission or low disease activity at 4 months had a cumulative survival rate of 90% until 24 months (P = .001). Conversely, early adverse reactions were reported as a cause of subsequent drug discontinuation (P = .001).

Although the study was the first to use real life data of a large sample of patients in the Lazio region, investigators noted the retrospective design and the fact it did not examine switching between biosimilars limited the analysis.

With a view to personalized medicine, the identification of all the demographic and anamnestic characteristics of the patient will be essential for the identification of a patient profile more suitable for a bDMARD rather than another,” investigators concluded.


  1. Gioia C, Picchianti Diamanti A, Perricone R, et al. Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies. Reumatismo. 2023;75(4):10.4081/reumatismo.2023.1602. Published 2023 Dec 19. doi:10.4081/reumatismo.2023.1602
  2. Elliot MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994; 344: 1105-10.