Real-World Evidence Shows Switching Among ESAs in CKD Is Not Associated With Risks to Safety, Efficacy

June 24, 2019
Kelly Davio

No statistically significant risk in terms of lack of effectiveness or safety was found for patients who switched therapies versus those who remained on their first therapy in either the reference group or the biosimilar group.

Erythropoiesis-stimulating agents (ESAs) play a crucial role in treating chronic kidney disease (CKD), and biosimilars, which have been available for more than a decade, have a major presence in Italy, where they account for approximately 51% of all ESAs used. Switching among ESAs is also relatively common in Italy, and a large-scale Italian observational study published last week reported that switching among ESAs in patients with CKD was not associated with impacts to efficacy or safety.

In the study, the researchers used multiple databases in 4 Italian geographical areas, and they assessed all 14,400 individuals with CKD who initiated treatment with ESAs between 2009 and 2015. Switching was defined as any transition between a reference ESA (Eprex), a biosimilar ESA (Abseamed, Binocrit, Retacrit), or any other ESA (such as short-acting epoetins like Neorecormon or long-acting epoetins like Aranesp, Nespo, or Mircera) for at least 2 prescriptions.

The researchers matched switched patients to nonswitched patients and followed them for up to 1 year after the switch date. Outcomes of interest were effectiveness and safety of ESAs; blood transfusions or anemia were considered indicative of lack of effectiveness, and major cardiovascular events, dyscrasias, and hypersensitivity were considered indicative of safety issues.

In total, 8843 (61.4%) patients started treatment with the reference product, while 5557 (38.6%) received a biosimilar. In the 2 groups, the percentages of patients who switched to another agent within 2 years were 21.1% and 11.5%, respectively.

In the reference group, most switches were to long-acting agents (58.5%), while 14.2% switched to a biosimilar. In the biosimilar group, most switches were to the reference (43.1%).

Overall, the investigators say lack of efficacy or safety issues occurred in 7.7% and 4.5%, respectively, of patients in the reference group. In the biosimilar group, the corresponding percentages of patients were 7.8% and 4.0%.

No statistically significant risk in terms of lack of effectiveness or safety was found for patients who switched therapies versus those who remained on their first therapy in either the reference group or the biosimilar group.

According to the authors, while the European Medicines Agency does not regulate interchangeability of biosimilars and reference products, Italy has taken the position that biosimilars and their references can be treated as interchangeable by prescribers, and this study has demonstrated that switching among ESA products is effective and safe in comparison with continued treatment with a single product.

“These results may be very useful to support clinical decisions related to switching drug therapies and promote better health policies to improve the uptake of biosimilars in the population,” they write.

Reference

Belleudi V, Trotta F, Addis A, et al. Effectiveness and safety of switching originator and biosimilar epoetins in patients with chronic kidney disease in a large-scale Italian cohort study [published online June 21, 2019]. Drug Saf. doi: 10.1007/s40264-019-00845-y.