Real-World Data Support the Noninferiority of Biosimilar Filgrastim in Preventing FN

Zarxio, a biosimilar filgrastim approved in the United States in 2015, was demonstrated to have no clinically meaningful differences from its reference in a randomized clinical trial setting, but data on its effectiveness in preventing febrile neutropenia (FN) a real-world setting have been limited thus far. A newly published study, which used retrospective observations from healthcare administrative claims, compared the incidence of FN—as well as the incidence of serious adverse events (AEs)—in patients taking the reference filgrastim (Neupogen) and in patients taking the biosimilar.

The study, published in the Journal of Managed Care & Specialty Pharmacy, used the Humana Research Database to identify patients (n = 189) with a medical or pharmacy claim for either the reference Neupogen (n = 88) or the biosimilar Zarxio from October 1, 2015, to September 30, 2016, within 6 days of exposure to chemotherapy.

The proportion of patients who had an FN outcome that resulted in hospitalization and the proportion of patients who experienced a serious AE after receiving filgrastim were observed in the 14 days following the claim. FN requiring hospitalization was defined in 2 ways: first, hospitalization with a diagnosis of either neutropenia or infection; and second, hospitalization with both neutropenia and infection diagnoses. Serious AEs considered were spleen rupture, acute respiratory syndrome, allergic reactions, capillary leak syndrome, thrombocytopenia, leukocytosis, cutaneous vasculitis, and bone and muscle ache.

In comparing reference and biosimilar filgrastim, noninferiority was established on incidence of FN requiring hospitalization; based on the 2 above definitions, the incidence differences between the 2 therapies were —0.6% (90% CI, –5.1%-4.0%, P =.84) and —0.8% (90% CI, –3.8%-2.1%, P =.64), respectively. The biosimilar had a higher—but nonsignificant—incidence of serious AEs (2.5%; 90% CI, —7.5%-2.5%, P =.42). The difference was, the authors note, too large to establish noninferiority.

These findings, say the authors, are some of the earliest published results examining the real-world clinical equivalency of biosimilars with their references, and provide a new picture of noninferiority between reference filgrastim and its biosimilar. The study was limited by the fact that data were derived from the Humana Research Database only, so results may not be generalizable to all patient populations. Furthermore, the study outcomes (as well as observation of serious AEs) were limited by the relatively small number of patients included.

However, the authors conclude that the reference Neupogen and filgrastim were noninferior for prevention of FN requiring hospitalization, though noninferiority based on the incidence of differences for serious AEs was not established.