Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy

Abstract

ObjectivesTo evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.DesignPopulation-based observational cohort study.SettingAll residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014.ParticipantsOverall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively.InterventionsESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period.Outcome measuresEffectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression.ResultsWe found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting.ConclusionsIn both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

Epoetin Biosimilars in the Treatment of Chemotherapy-Induced Anemia: 10 Years’ Experience Gained

“…Data from the ORHEO (place of biOsimilaRs in the therapeutic management of anemia secondary to chemotherapy in HaEmatology and Oncology) observational study ( n = 2333) in France, conducted primarily in patients using SB309, indicate a post-marketing safety profile consistent with the reference epoetin alfa [ 30 , 31 ]. More recently, a population-based observational cohort study of more than 13,000 patients reported no difference in safety outcomes between treatment with biosimilar epoetins, reference epoetin alfa, and other ESAs [ 32 ]. Thus, for those initially concerned about the safety of epoetin biosimilars, reassurance is provided by data now accumulated, which demonstrate that there have been no specific safety signals after 10 years of clinical usage in Europe.…”

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

“…The only RCT in patients with cancer 30 had a high likelihood of bias based on inadequate sample size, lack of an intent-to-treat analysis, and industry funding and authorship. The quality of the four included cohort studies of biosimilars [31][32][33][34] in patients with cancer was not formally assessed.…”

“…The systematic review of biosimilar ESAs included two metaanalyses 27,28 and one RCT 29 in patients with CKD, and one RCT 30 and three cohort studies [31][32][33] in patients with cancer. In a 2017 meta-analysis of RCTs in CKD, Amato et al 27 reported that efficacy and safety outcomes did not differ significantly between patients treated with epoetin alfa originator or biosimilar but described the quality of evidence as low to very low.…”

“…A large retrospective population-based cohort study in Italy evaluated more than 13,000 new ESA users, 8161 with CKD and 5,309 with cancer. 33 A biosimilar epoetin alfa had been used by 154 (1.9%) of the patients with CKD and 453 (8.5%) of the patients with cancer. Biosimilar and originator epoetin alfa had similar safety and efficacy in both CKD and cancer with one exception: among patients with cancer, biosimilar epoetin alfa was associated with lower overall mortality than the originator (HR, 0.82; 95% CI, 0.70 to 0.97), but this finding is not conclusive because residual confounding could not be excluded since more patients in the originator group died of cancer activity.…”

Let us use physiologic transfusion triggers: Favorable outcome in an 86-year-old Jehovah's witness with a haemoglobin nadir of 44g L-1

“…Guidelines also advise compensating any hematinic deficiencies with erythropoiesis-stimulating agents, iron, folic acid and vitamin B12 [3]. In our case, we used epoetin alfa intravenously as oppose to subcutaneous route, as it allows faster patient response and greater flexibility in terms of dosing [4].…”