Biosimilar adalimumab (GP2017; Novartis, Sandoz) and biosimilar etanercept (GP2017; Novartis, Sandoz; SB4; Samsing Biopis) have shown equivalent effectiveness over a 48-month period compared to Humira (AbbVie) and Enbrel (Amgen), respectively, according to results of a study published in Clinical Drug Investigation. Further, the investigators said the levels of disease activity after 6 months of tumor necrosis factor-α inhibitors (TNF-α) could help predict the response to therapy at 4 years for those who have long-standing rheumatoid arthritis (RA).
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Biosimilar interchangeability is highly debated, despite any advantages biosimilar drugs might provide, according to the study authors. Currently, guidelines recommend biosimilar usage as first-line treatment for patients with moderate to severe RA who did not response to conventional disease-modifying drugs. However, the investigators noted that patients with RA who use TNF-α inhibitors might respond to treatment differently. Initial changes in disease activity have the potential to predict a late treatment response.
3 Key Takeaways
- The study indicates that biosimilar adalimumab and etanercept demonstrate equivalent effectiveness to their reference products, Humira and Enbrel, respectively, over a 48-month period in patients with long-standing rheumatoid arthritis (RA).
- Researchers suggest that early changes in disease activity levels, particularly within the first 6 months of treatment with tumor necrosis factor-α inhibitors (TNF-α), may help predict long-term responses to therapy for individuals with RA.
- Biosimilar adalimumab showed a more favorable survival curve compared to biosimilar etanercept, indicating potential variations in patient adherence or tolerability between the two drugs.
The study investigators aimed to compare the clinical efficacy of biosimilars with the reference products over a 48-month period. In the study, they also wanted to determine when it is possible to predict responses to therapy for those with long-standing RA, according to the study authors.
Participants were divided into 4 groups according to their treatment with the biosimilars or reference products. All individuals were treated following the current guidelines and received 5 years of long-term follow up from August 2017 to August 2022, according to the study authors. Data were collected every 6 months and routine monitoring of disease activity for 48 months was performed. Investigators used the 28-Joint Disease Activity Score (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) to evaluate the disease activity, according to the study authors.
There were 1598 individuals included in the study, 1219 of whom were female. The mean age of the reference product recipients was 65 years for etanercept and 63 years for adalimumab, and 58 years and 60 years for the biosimilar drugs, respectively. The average time from diagnosis to treatment was 74, 49, 66, and 71 months, respectively. Investigators reported no differences in treatment based on methotrexate or leflunomide with the reference or biosimilar agent, according to the results.
There was no difference between either drug and their biosimilar(s) in the study, according to the study authors. In the first 18 months of administration, there was a significant improvement in all scores for all 4 groups of treatment. Between the 18 and 48 months, FAS28, SDAI, and CDAI levels flattened for all 4 groups. The clinical efficacy of all 4 drugs were at the maximum after 24 months and lasted for up to 48 months, the study authors said.
However, even with the efficacy being the same between reference product and biosimilar, the analysis of survival probability showed significant differences in the 48 months. In both groups, the survival probability with the biosimilar remained high until 24 months of administration, then the distance between the curves increased for both sets of drugs. Investigators noted that the overall drug survival curve for biosimilar adalimumab and reference product was more favorable than the biosimilar for etanercept and its reference product.
Furthermore, there were no data available for cause of dropout, but the study authors said that there were a high number of patients who stopped the study in the reference drug group, and were also the oldest, according to the results.
Colina M, Khodeir M, Rimondini R, Valentini M, et al. Forty-Eight-Month Monitoring of Disease Activity in Patients with Long-Standing Rheumatoid Arthritis Treated with TNF-α Inhibitors: Time for Clinical Outcome Prediction and Biosimilar vs Biologic Originator Performance. 2024. Clin Drug Investig. doi:10.1007/s40261-024-01341-7