Biosimilar epoetins under safety scrutiny

Chronic renal failure represents nowadays one of the biggest public health issues worldwide: it is estimated that in Italy one person over seven people has a moderate impairment of the renal function, i.e. a halved renal functionality, or more than halved, in comparison with the norm.¹ Chronic renal failure causes the progressive and irreversible loss of the renal functions up to a terminal stage when, inevitably, a substitutive treatment such as dialysis or renal transplant becomes necessary. Besides, chronic nephropathy is generally associated to the onset of anaemia, whose principal cause is the inadequate synthesis of erythropoietin (Epo) by the peritubular interstitial cells of the kidney. Before injectable erythropoietin became available, transfusions were the only way to correct anaemia, with all the risks involved; in 1988, thanks to the recombinant DNA technique, the first epoetin alfa approved for clinical use was commercialized, which later became the forefather molecule of the erythropoietin stimulating agents (ESA). In particular, the guidelines recommend the use of recombinant erythropoietin in anaemia associated to chronic renal failure in patients under dialysis in order to maintain the haemoglobin between 10 and 12 g/dl. After the patent expired, in 2004, the European Agency for Medicines (EMA) approved three versions of biosimilar epoetin, i.e. biologically active molecules comparable with the originator drug in terms of quality, safety and effectiveness.
Despite the good reception of the biosimilars by the scientific community - as they allowed reducing the pharmaceutical expense, consequently granting therapy access to more patients - a certain diffidence about their use still remains, partly due to missing information on the approval process and also because of concerns regarding a presumed higher toxicity of the biosimilars than the originator drugs.^2,3
In light of these hesitations, the Veneto region promoted a prospective multicentre cohort trial funded in the framework of the AIFA interregional projects on pharmacovigilance, whose data collection started at the end of 2013, which involved three more Italian regions (Liguria, Molise and Sardinia). ESAVIEW is a pharmacovigilance trial that aims to compare the originator epoetin with the biosimilars in terms of safety, evaluating the incidence of adverse events, and on a second level, of effectiveness by DDDs (defined daily doses) counting.
On the starting date, patients under dialysis whom were already been treated with epoetin (prevalent cases), were included, whilst in the following 6 months new users (incident cases) were enrolled. Each patient was observed, when possible, for 12 months, or anyway until leaving the study for death, transplant or transfer to peritoneal dialysis or to another centre not included in the experimentation. Purportedly trained monitors registered monthly over an online platform the data regarding intradialysis therapy, home therapy, some significant lab parameters, possible transfusions and serious events that required emergency care or hospitalisation. The aim of the study was therefore to collect information about what usually happens in the haemodialysis centres, particularly regarding the epoetin therapy management on patients under dialysis. This is just an anticipation of the study, once the analysis is concluded we will provide the results in a more detailed article.