Observational Study Confirms Safety Profile of Biosimilar Epoetin Alfa in Nephrology

While the United States is still awaiting the launch of the first FDA-approved biosimilar epoetin alfa, erythropoiesis-stimulating agents were among the first biosimilars to become available in Europe. This month, Italian researchers published a post-authorization observational study that compared the efficacy and safety of European biosimilars and the reference epoetin alfa in patients undergoing dialysis at 26 hospitals in 4 regions in Italy, and they concluded that their results support the comparable safety profiles of the originator and biosimilar products.

The study, conducted between 2013 and 2015, included all adult patients with chronic kidney disease who had hemodialysis at least twice weekly and who were treated with the innovator epoetin (Eprex) or a biosimilar (Binocrit or Retacrit). Each patient was followed for 12 months after the first visit.

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The study’s outcomes comprised 3 major categories: problems related to the dialysis device (such as infections of the vascular access), cardiovascular or cerebrovascular events (such as arrhythmia that was not present at baseline), and infections (such as pneumonia).

A total of 423 patients used the originator and 444 used one of the biosimilars (440 of the biosimilar users received Binocrit). Patients who took a biosimilar were older than those who took the reference, and were more frequently affected by arrhythmia and diabetes at baseline. Those who used the originator more frequently had arteriovenous fistula and previous renal transplant, and were more frequently on transplant wait lists and had received dialysis for a longer time. There were 765 established epoetin users and 102 new patients.

A total of 274 patients (31.6%) experienced at least 1 of the safety outcomes; 123 events (29.1%) occurred in patients using the reference product and 151 (34.0%) occurred among the biosimilar users. The most common events were infections (11.5%), followed by cardiovascular and cerebrovascular conditions (10.6%), followed by problems related to the dialysis device (9.8%). A total of 127 deaths occurred in the study population (14.6%) during the 12-month follow-up period.

After adjusting for confounding factors (such as age, vascular access, heart failure, and other conditions), hazard ratio estimates were 1.0 (95% CI, 0.7-1.3) for any of the study outcomes, 0.9 (95% CI, 0.6—1.5) for infections, 0.9 (95% CI, 0.6-1.5) for cardiovascular and cerebrovascular conditions, and 1.1 (95% CI, 0.7-1.8) for device-related problems.

Results were similar to the overall population when new patients were considered as a subgroup; 33 patients (32.4%) experienced at least 1 safety outcome, and there was no statistically significant difference between biosimilar or reference users.

“The results from this study confirm the similarity in terms of safety between originator [epoetin alfa] and biosimilars when used in patients with [chronic kidney disease] receiving dialysis,” concluded the authors. “Specifically, no difference emerged between the [2] cohorts of users with regard to any kind of adverse events.”

Reference

Stoppa G, D’Amore C, Conforti A, et al. Comparative safety of originator and biosimilar epoetin alfa drugs: an observational prospective multicenter study. BioDrugs. 2018;32: 367. doi: 10.1007/s40259-018-029.