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

Abstract

Introduction: Real-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.

Objective: The 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.

Methods: An 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.

Results: Overall, 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 categories CONCLUSIONS: In 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.

Fig. 1

Study design. Switchers (S) were matched with non-switchers (NS) 1:1 by propensity score (caliper = 0.10) and time in treatment with first epoetin alpha (ESA α) (± 30 days). ESA erythropoiesis-stimulating agent, max maximum

Fig. 2

Study population. ESA erythropoiesis-stimulating agent, ESA α epoetin alpha

Fig. 3

Switching time in originator (a) and biosimilar (b) initiator groups

Fig. 4

Adjusted hazard ratios (HRs) and sensitivity analyses for all considered outcomes in epoetin alpha initiator groups. a HR lack of effectiveness outcomes for switchers versus non-switchers in the originator initiators group; b HR lack of effectiveness outcomes for switchers versus non-switchers in the biosimilar initiators group; c HR safety outcomes for switchers versus non-switchers in the originator initiators group; and d HR safety outcomes for switchers versus non-switchers in the biosimilar initiators group. Subgroup analysis 1: subject with a more conservative definition matching, i.e. time in treatment with first epoetin alpha ± 15 days. Subgroup analysis 2: subjects switching within 180 days from beginning of first epoetin alpha treatment. CI confidence interval, ESA erythropoiesis-stimulating agent, Fup follow-up

Fig. 5

Cumulative probabilities of recording a lack of effectiveness (a) or safety event (b) between epoetin switchers. ESA α epoetin alpha