No Differences in Long-Term Drug Survival Between Biosimilar, Originator TNF Inhibitors

No significant differences in long-term survival due to inefficacy or adverse events were found between subcutaneous biosimilar and originator tumor necrosis factor (TNF) inhibitors for rheumatic diseases, as shown by a retrospective analysis published in The Journal of Rheumatology.¹

“In real-world practice, this can be reassuring when deciding to start a biosimilar. Concomitant [methotrexate] was associated with higher retention rate, and its use should be considered when appropriate,” the authors suggested.

The study aimed to compare drug survival and discontinuation rates of subcutaneous biosimilar TNF inhibitors (etanercept and adalimumab) with their originator counterparts (Enbrel and Humira, respectively) in Spanish patients with rheumatic diseases, addressing concerns about biosimilars' effectiveness and safety. The authors said the results are crucial for evaluating the real-world performance of biosimilars, informing treatment choices, and guiding policies on their use in clinical practice.

As of March 2024, the European Union has 10 adalimumab biosimilars and 3 etanercept biosimilars.² TNF inhibitors are used to treat numerous rheumatic conditions, including ankylosing spondylitis, rheumatoid arthritis, juvenile idiopathic arthritis, uveitis, ulcerative colitis, and Crohn disease.

Researchers conducted as a retrospective analysis of the BIOBADASER registry, a Spanish multicenter observational database tracking patients with rheumatic diseases on biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs). The analysis included patients who started treatment with original or biosimilar etanercept or adalimumab from January 2016 to October 2023. Data on patient demographics, disease characteristics, and treatment outcomes were collected, with retention rates analyzed to identify factors influencing drug discontinuation.

Interestingly, biosimilars were more commonly prescribed as first-line treatments compared with originators (62.18% vs 47.78%; P < .001) and were used more frequently in combination with methotrexate (41.94% vs 35.87%; P = .001), other conventional synthetic DMARDs (22.99% vs 18.01%; P = .003), and corticosteroids (36.32% vs 31.58%; P = .01). Patients receiving biosimilars started therapy at an older average age compared with those on originators (52.2 vs 48.4 years; P < .001) but had a shorter disease duration at the start of treatment (8.3 vs 9.3 years; P = .01). No other significant differences in clinical characteristics were observed between the 2 groups.

Overall, 1720 (36.42%) treatment courses were discontinued by the end of the study, while 3003 (63.58%) were ongoing. Biosimilars had a significantly lower discontinuation rate compared with originators (33.37% vs 53.32%; P < .001). The primary reason cited for discontinuation was inefficacy (60.35%), followed by adverse events (17.85%). Significant differences in discontinuation reasons were observed, with biosimilars more frequently discontinued due to inefficacy and adverse events, while originators were more often discontinued due to remission (P < .001).

Survival curves and log-rank tests showed a greater retention rate for biosimilars (P = .003) in overall drug discontinuation, though no significant differences were found in cause-specific discontinuations. The Cox regression model revealed a lower risk of overall discontinuation for biosimilars (adjusted HR, 0.84; 95% CI, 0.75-0.95; P = .01). Factors increasing the risk of discontinuation included female sex (P = .001), obesity (P = .03), and being on second or third-line treatments (P = .03 and.001, respectively). Concomitant use of methotrexate (P = .001) and longer disease duration (P < .001) were associated with a lower risk of discontinuation, and patients with spondyloarthritis had a lower risk compared to those with rheumatoid arthritis (P = .03). There were no significant differences in cause-specific discontinuation risks between biosimilars and originators in either crude or adjusted analyses.

This study is the first to compare the survival rates of both adalimumab and etanercept biosimilars with their originators in patients, including those with juvenile idiopathic arthritis. Limitations included potential clinician bias towards biosimilars, lack of differentiation among originator brands, and possible residual confounding due to unmeasured factors.

References

1. Martínez-Vidal MP, Fernández-Carballido, Otero-Varela L, et al. Long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to originators: results from a multicenter prospective registry. J Rheumatol. Published online August 1, 2024. doi:10.3899/jrheum.2024-0001

2. Biosimilar approvals. The Center for Biosimilars^®. Updated March 22, 2024. Accessed August 12, 2024. https://www.centerforbiosimilars.com/biosimilar-approvals