Effectiveness and Safety of Switching Originator and Biosimilar Epoetins in Patients with Chronic Kidney Disease in a Large-Scale Italian Cohort Study

Abstract

IntroductionReal-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients.ObjectiveThe objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA α) to any other epoetin in CKD patients.MethodsAn observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA α dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA α to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA α treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA α to any other epoetin) was also performed.ResultsOverall, 14,400 incident users of ESA α for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79–1.31 originators; HR 1.16, 95% CI 0.75–1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77–1.50 originators; HR 1.20, 95% CI 0.66–2.21 biosimilars) between switchers and non-switchers of ESA α. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categoriesConclusionsIn this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes.Electronic supplementary materialThe online version of this article (10.1007/s40264-019-00845-y) contains supplementary material, which is available to authorized users.

Dose equivalency and efficacy of biosimilar erythropoietin stimulating agents: Data from real clinical practice

“…Despite the proven comparability of the efficacy and safety of biosimilar to the originator medicine and the great opportunity for cost saving, the acceptance of biosimilar agents among the medical community remains limited in some countries and therapeutic areas. 6 There are several cited reasons that could explain the lack of enthusiasm toward biosimilars, including the lack of provider confidence, uncertainty about substitution, and a lack of patient awareness and education. 12 In Kazakhstan, bESA become available in 2017, after which a few dialysis centers switched their patients to the newly introduced alternative.…”

“…5 In addition to being a cost saving phenomenon, switching to biosimlars is something to be considered as a medical issue, particularly if it could occur with other medicines as well. 6 Since the year 2017, biosimilar ESA (bESA) have become available in Kazakhstani trade. Due to their lower prices compared to originator (rESA), a few of the country's dialysis centers switched their patients to bESA.…”

Sun-275 Dose Equivalency and Efficacy Of biosimilar Erythropoietin Stimulating Agents: Data From Real Clinical Practice

“…Despite the proven comparability of the efficacy and safety of biosimilar to the originator medicine and the great opportunity for cost saving, the acceptance of biosimilar agents among the medical community remains limited in some countries and therapeutic areas 6 . There are several cited reasons that could explain the lack of enthusiasm toward biosimilars, including the lack of provider confidence, uncertainty about substitution, and a lack of patient awareness and education 12…”

“…This would also provide major advantages for patients and communities such as that financial resources may be more efficiently allocated to other important uses, which makes more innovative therapies available to patients 5 . In addition to being a cost saving phenomenon, switching to biosimlars is something to be considered as a medical issue, particularly if it could occur with other medicines as well 6 …”

Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?

“…Observational studies of the use of epoetins and granulocyte colony-stimulating factors in patients with chronic kidney disease or cancer in Italy have demonstrated that there is frequent switching between different biological products belonging to the same class in routine clinical care [24,25]. Post-marketing studies conducted in population-based databases have provided additional evidence of the comparative effectiveness and safety of originator and biosimilar epoetins, and have shown that switching from originator epoetin to a biosimilar epoetin, or vice versa, is safe and effective [26][27][28].…”