Etanercept and Infliximab Biosimilars Show No Increased Infection Risk, Comparable Safety

No significant difference in the risk of serious infections between etanercept and infliximab biosimilars and their original brand-name medications was identified. | Image Credit: Ouahdou - stock.adobe.com

Patients treated with etanercept and infliximab biosimilars experience a similar risk of serious infections as those treated with the original brand-name drugs, potentially offering patients access to safe and more affordable treatment options, according to a study published in BMC Rheumatology.¹

Biologic drugs are gaining popularity, especially for the management of autoimmune diseases like inflammatory arthritis and inflammatory bowel disease (IBD). Real-world comparative studies prioritize safety assessment, examining the long-term effects of both biosimilars and bio-originators.

Global skepticism regarding biosimilar safety persists, necessitating ongoing requirements for switching studies to ensure their efficacy and safety.² Previous studies have found infliximab biosimilars effective and well-tolerated after switching, with no discontinuations or clinical changes within 6 months.

Following the CMS announcement that etanercept is among the 10 drugs selected for price negotiation under the Inflation Reduction Act, increased competition from biosimilars is anticipated within the next few years.³ Etanercept biosimilars are expected to launch in 2029 following the resolution of patent litigation with the original manufacturer. This delay has implications for patient access and affordability of this medication used to treat rheumatic diseases.

Administrative databases are often used as real-world data that can “enable long-term safety assessments in populations not eligible for clinical trials but at higher risk of serious infection and may capture missed rare adverse events.”¹

This retrospective cohort study compared the occurrence of serious infections in Canadian patients with autoimmune diseases treated with etanercept or infliximab biosimilars vs their corresponding bio-originator from 2015 to 2019. Data included the National Prescription Drug Utilization Information System linked to the hospital Discharge Abstract Database.

There were 6583 and 7202 individuals who initiated etanercept and infliximab, respectively. The etanercept cohort was mostly women with a median age of 62 and about 10% had an inflammatory arthritis diagnosis. Half of the infliximab cohort were women with a median age of 45 but only 2% were identified with inflammatory arthritis and 35% with IBD. Both cohorts had a median follow-up period of 2.2 years.

More patients taking infliximab experienced hospitalization due to infection (7%) compared with patients taking etanercept (2%). Additionally, incidence rates for serious infection among infliximab users (30 cases per 1000 person-year [PY]) was higher than it was for etanercept (9 cases per 1000 PY).

There were no clear differences identified in the risk of incidence of serious infection between biosimilar and bio-originator for both cohorts, even when adjusted for confounders. Higher infection risk was found among both etanercept and infliximab groups after independent corticosteroid use was previously noted. Older age was found to be a risk factor for infection in etanercept initiators.

Patients with inflammatory arthritis treated with etanercept (n = 695) or with infliximab (n = 154) did not have a clear difference between biosimilar and bio-originator use in terms of first serious infection. Individuals with IBD diagnosis treated with infliximab (n = 2506) did not have an established difference between biosimilar vs bio-originator in terms of serious infection.

Study limitations include potential widespread selection bias and the availability and consistency of data elements across different jurisdictions that may vary and require consideration during data analysis and interpretation. This is also like other claims databases that lack clinical and laboratory details that may neglect to fully assess disease severity and treatment response.

There are limited real-world studies that have addressed the safety of etanercept and infliximab in large populations because most of them have focused on comparing the first biosimilar to its corresponding bio-originator, often overlooking other competitors.

The study was unable to demonstrate a difference regarding hospitalized infection risk when comparing biosimilars and their corresponding bio-originators. Utilizing ongoing safety methods, “we can enhance our understanding of the safety profiles of biosimilars and foster evidence-based decision-making in managing chronic inflammatory diseases,” concluded study authors.

References

1. Birck MG, Lukusa L, Choquette D, et al. Incidence of serious infection among etanercept and infliximab initiators: safety comparison between biosimilars and bio-originators with Canadian population-based data. BMC Rheumatol. 2024;8(1):47. doi:10.1186/s41927-024-00415-5

2. Jeremias S. New evidence confirms safe biosimilar-to-biosimilar switching. The Center for Biosimilars^®. May 28, 2024. Accessed January 2, 2025. https://www.centerforbiosimilars.com/view/new-evidence-confirms-safe-biosimilar-to-biosimilar-switching

3. Jeremias S. CMS announces new drug prices under the IRA, including for Stelara and Enbrel. The Center for Biosimilars. August 19, 2024. Accessed January 2, 2024. https://www.centerforbiosimilars.com/view/cms-announces-new-drug-prices-under-the-ira-including-for-stelara-and-enbrel