Canadian Real-World Study Finds No Increased Infection Risk with TNF Inhibitor Biosimilars

A comprehensive real-world analysis of Canadian administrative health data has demonstrated comparable serious infection (search)Search disease rates between biosimilar (search)Search drug and originator versions of two major TNF (search)Search target inhibitors, providing reassuring evidence for the safety profile of these cost-effective alternatives in clinical practice.

The retrospective cohort study, conducted using data from the National Prescription Drug Utilization Information System (NPDUIS) linked to hospital discharge records, analyzed 13,785 adults who initiated infliximabView drug details (7,202 patients) or etanerceptView drug details (6,583 patients) between 2015 and 2019. The research represents one of the largest real-world safety comparisons of TNF inhibitorView drug details biosimilars to date.

Key Safety Findings

The analysis revealed no statistically significant difference in serious infection (search)Search disease risk between biosimilar (search)Search drug and originator formulations for either drug. For infliximabView drug details, the adjusted hazard ratio for serious infection with biosimilars was 0.93 (95% CI 0.72-1.18), while etanerceptView drug details biosimilars showed an adjusted hazard ratio of 1.33 (95% CI 0.77-2.30) compared to their respective originators.

Notably, infliximabView drug details users experienced substantially higher infection rates overall, with 30 cases per 1,000 person-years compared to 9 cases per 1,000 person-years for etanerceptView drug details users. Approximately 7% of infliximab patients required hospitalization due to infection, contrasting with only 2% of etanercept patients during the study period.

Patient Demographics and Treatment Patterns

The study populations showed distinct demographic characteristics reflecting typical prescribing patterns. EtanerceptView drug details users were predominantly female (64.5%) with a median age of 62 years, while infliximabView drug details users were evenly split by gender with a younger median age of 45 years. The analysis included patients across multiple indications, with 35% of infliximab users identified with inflammatory bowel disease (search)Search disease and 10.6% of etanercept users with inflammatory arthritis.

Median follow-up duration was 2.2 years for both drug cohorts, providing substantial observation time to capture serious infection (search)Search disease events. The study period coincided with Canadian biosimilar (search)Search drug implementation policies, with mandatory biosimilar use for new infliximabView drug details patients beginning around mid-2016 and for etanerceptView drug details around mid-to-late 2017.

Risk Factors and Clinical Implications

The multivariate analysis identified several independent risk factors for serious infection (search)Search disease. Prior corticosteroid (search)Search drug use emerged as a significant predictor for both drugs, with hazard ratios of 1.75 (95% CI 1.25-2.44) for etanerceptView drug details and 1.76 (95% CI 1.47-2.11) for infliximabView drug details. Advanced age (≥65 years) specifically increased infection risk among etanercept users.

Geographic variations were also observed, with patients in Ontario province showing elevated infection rates for both medications. This finding likely reflects provincial differences in biosimilar (search)Search drug adoption policies and patient demographics, as Ontario was among the last provinces to implement mandatory biosimilar policies and its public drug coverage primarily serves older adults.

Addressing Evidence Gaps

The research addresses significant gaps in biosimilar (search)Search drug safety evidence, particularly for etanerceptView drug details biosimilars where real-world infection data has been limited. Previous studies have predominantly focused on early infliximabView drug details biosimilars, particularly CT-P13View drug details, often with shorter follow-up periods and more restricted patient populations from randomized controlled trials.

The Canadian findings align with existing evidence from clinical trials and registries but provide broader population-based insights. The infection rates observed (8.3% for infliximabView drug details) were higher than those reported in randomized trials (~1%), likely reflecting real-world patient complexity and longer observation periods compared to controlled study environments.

Study Strengths and Limitations

The analysis leveraged comprehensive administrative databases covering all Canadian provinces except Quebec, providing population-level insights into biosimilar (search)Search drug safety. The linked prescription and hospitalization data enabled long-term safety monitoring across diverse patient populations and clinical indications.

However, the researchers acknowledged several limitations, including inability to identify specific drug indications for most patients and potential selection bias toward more severe cases requiring hospitalization. The databases also lacked detailed clinical information about disease severity and laboratory parameters that could influence infection risk.

Clinical and Policy Implications

These findings support the continued adoption of TNF inhibitorView drug details biosimilars in clinical practice, providing healthcare systems with cost-effective alternatives without compromising patient safety. The comparable infection profiles between biosimilars and originators reinforce regulatory approval decisions and biosimilar (search)Search drug substitution policies implemented across Canadian provinces.

The research contributes valuable real-world evidence to the growing body of biosimilar (search)Search drug safety data, particularly important as healthcare systems worldwide increasingly rely on these alternatives to manage rising biologic therapy costs while maintaining treatment access for patients with inflammatory conditions.