Making “Rheum” for Biosimilars: Overcoming Reluctance

Despite the proven efficacy of biosimilars, both patients and health care providers often have some reluctance when switching from an originator drug to a biosimilar.

Tumor necrosis factor-α (TNF-α) drives systemic inflammation in immune-mediated diseases such as RA. Macrophages, CD4(+) T cells, mast cells, neutrophils, and natural killer cells produce TNF-α. When TNF-α binds to its receptors, expression of pro-inflammatory cytokines (e.g., interleukin-1, interleukin-6, and interleukin-8) increases. Treatment with TNF-α inhibitors yields widely varied clinical response among patients. Individuals with high baseline disease activity and long disease duration are more sensitive to these treatments.¹

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Now, a study published ahead of print for the January 2024 issue of Clinical Drug Investigation provides timing to predict long-term response to TNF-α inhibitors. The study also compares biosimilars’ clinical efficacy with their biological reference drugs, adalimumab and etanercept.²

The study researchers monitored patients with long-standing RA and high disease activity for 48 months to determine a time for clinical outcome prediction. Every 6 months, they evaluated disease activity scores using 28-Joint Disease Activity Score (DAS-28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). The researchers assessed treatment efficacy comparing the three indices within each patient group: adalimumab vs biosimilar (GP2017) and etanercept vs biosimilars (GP2015/SB4). Patients with a DAS28 score reduction of at least 1.2 points (representing major improvement in RA disease activity) were deemed responders, whereas patients without a DAS28 score improvement of at least 1.2 points were deemed non-responders (primary inefficacy). This study defined secondary inefficacy as efficacy loss to a previous treatment over time.²

The researchers observed decreased disease activity in patients with a good and persistent response to therapy at the 6-month follow up. Disease activity levels after 6 months of treatment with TNF-α inhibitors identified long-term responders and predict response to therapy at 4 years. Identifying long-term responders allows for appropriate clinical decisions and personalized therapy.¹

Compared with patients receiving corresponding biosimilars, the researchers observed similar disease activity levels among patients receiving adalimumab or etanercept. Activity scores significantly declined in all treatments during the first 18 months of therapy. After 24 months, originator drugs and their biosimilars reached a maximum clinical efficacy that lasted up to 48 months. The researchers concluded that biosimilars of adalimumab and etanercept have equivalent effectiveness, minimizing disease activity in patients with long-standing RA, and are less expensive than their originator drugs. This study is the first to show a fully comparable long-term efficacy trend between adalimumab, etanercept, and their biosimilars.²

Biosimilars offer price competition, providing significant economic benefits to the health care system and improving access to therapy. This study contributes data to help overcome both physicians’ and patients’ reluctant attitudes toward switching to biosimilars. Researchers recommend future studies include patients’ body mass index to further explore the potential impact on TNF secretion and treatments’ appropriateness.²

References

1. Colina M, Khodeir M, Rimondini R, 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. Clin Drug Investig. Published online January 31, 2024. doi:10.1007/s40261-024-01341-7

2. Rheumatoid Arthritis (RA). Centers for Disease Control and Prevention (CDC). Accessed February 2, 2024. Updated April 7, 2022. https://www.cdc.gov/arthritis/types/rheumatoid-arthritis.html