Etanercept, Infliximab Biosimilars Not Linked to Greater Infection Risks

Etanercept and infliximab biosimilars may not put patients at risk of infections any different from their originators, Enbrel and Remicade, respectively, according to new research.

A retrospective cohort analysis of Canadian data from the country’s prescription drug utilization information systems showed that, despite a trend of consumer and prescriber worry over safety outcomes with biologic options, such available products for etanercept and infliximab are not linked to significantly increased risks of infection—a key outcome associated with the autoimmune disease-treating agents.

The data add to the ever-growing library of findings supporting the safety profile of available biosimilar therapies indicated to treat chronic diseases, despite a slow uptick in their use and a general lack of knowledge surrounding the drug class.

Investigators led by Marina G. Birck, PhD, MSc, of the Research Institute of the McGill University Health Centre in Montreal, sought to compare the incidence of serious infection between biosimilars for etanercept and infliximab, and their originator initiators. Their rationale was that these biologics were among the most commonly used during the observed time period of 2015 – 2019—and that the biologic drug development industry is “rapidly expanding.”

“Given the complexity of biological molecules, safety remains a paramount concern,” investigators wrote. “As (inflammatory arthritis) and (inflammatory bowel disease [IBD]) biologic drugs downregulate the immune system, these individuals are prone to serious infection.”

Birck and colleagues conducted their retrospective cohort study observing new adult users of infliximab or etanercept—either the originator drug or an available similar—between 2015 – 2019. Incidence rates of serious infection (defined as a hospitalization) were compared between the originator and biosimilar arms, with Cox regression models used to interpret adjusted hazard ratios (aHRs). Investigators adjusted models with regard to biological sex, age at initiated treatment, prior corticosteroid or biologic use, Canada province, and calendar year.

The final analysis included 6583 patients initiating etanercept and 7202 patients initiating infliximab during the observed period. Specifically, 2019 patients received an infliximab biosimilar; 5183 received originator infliximab; 2085 received an etanercept biosimilar; and 4498 received originator etanercept.

Median follow-up was 2.2 years for both infliximab and etanercept arms. A majority of patients were female; median age was older in the etanercept cohort (62 years) versus the infliximab cohort (45 years). A higher rate of patients in the etanercept cohort had been diagnosed with arthritis (10%); one-third (35%) of the infliximab cohort had been diagnosed with IBD.

Overall, investigators observed 138 cases of serious infection among the etanercept arm (2.1%), versus 510 in the infliximab arm (7.1%). Overall incidence rates per 1000 patient-years for each arm were 8.90 (95% CI, 7.5 – 10.6) for etanercept and 30.1 (95% CI, 27.5 – 32.8) for infliximab.

Incidence rate of serious infection per 1000 patient-years was 11.8 (95% CI, 7.9 – 16.8) for the biosimilar etanercept arm versus 8.4 (95% CI, 6.9 – 10.1) for the originator etanercept arm. Rates were 33.4 (95% CI, 27.2 – 40.1) for the biosimilar infliximab arm, and 29.3 (95% CI, 26.6 – 32.3) for the originator infliximab arm.

Investigators observed no difference between the arms and time-to-first-event incidence for serious infections. However, prior corticosteroid use was independently linked to higher infection risk for both etanercept and infliximab, and older age was a risk factor for infection in the etanercept arm.

Among patients with arthritis treated with etanercept (n = 695; 44% on biosimilar) or infliximab (n = 154; 45% on biosimilar), the team observed no significant difference between biosimilar and originator risks of first serious infection:

• Etanercept (aHR, 1.69; 95% CI, 0.64 – 4.49)
• Infliximab (aHR, 1.74; 95% CI, 0.51 – 5.89)

Among patients with IBD treated with infliximab (n = 2506; 25% on biosimilar), investigators could again not establish a significant difference in serious infection risk between biosimilar and originator (aHR, 1.19; 95% CI, 0.86 – 1.64).

In reviewing the findings, Birck and colleagues described their results as “reassuring evidence of a comparable safety profile for biosimilars.”

“Using real-world administrative health care data, focusing on etanercept and infliximab, we were unable to demonstrate a clear difference regarding hospitalized infection risk when comparing biosimilars and their corresponding bio-originators, corroborating previous findings of randomized controlled trials and real-world evidence,” the team wrote. “With ongoing safety surveillance, we can enhance our understanding of the safety profiles of biosimilars and foster evidence-based decision-making in managing chronic inflammatory diseases.”

References

1. ^{Birck MG, Lukusa L, Choquette D, Boire G, Maksymowych WP, Singh H, Afif W, Bernatsky S. Incidence of serious infection among etanercept and infliximab initiators: safety comparison between biosimilars and bio-originators with Canadian population-based data. BMC Rheumatol. 2024 Sep 27;8(1):47. doi: 10.1186/s41927-024-00415-5. PMID: 39343928; PMCID: PMC11441163.}
2. ^{Pine L. Study Highlights Ongoing Need for Biosimilar Education Among Physicians, Pharmacists. HCPLive. Published May 31, 2024. https://hcplive.com/view/study-highlights-ongoing-need-for-biosimilar-education-among-physicians-pharmacists}