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Comparative efficacy and safety in ESA biosimilars vs. originators in adults with chronic kidney disease: a systematic review and meta-analysis

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Abstract

Background

Several Erythropoiesis-stimulating agents (ESAs) are available to treat anemia in patients with chronic kidney disease (CKD). Questions about the comparability of such therapeutic options are not purely a regulatory or economical matter. Appropriate use of originator or biosimilar in these patients need to be supported by clinical data. Regarding the prevention of blood transfusion, reduction of fatigue, breathlessness and mortality or cardiovascular events, a summary of the comparative efficacy and safety data of these drugs is lacking.

Methods

We performed a systematic literature search of CENTRAL, PubMed, and Embase through November 11, 2015. Our inclusion criteria encompassed randomized, controlled clinical trials that evaluated the comparative effectiveness of different ESAs originators and/or biosimilar. The considered participants were adults aged 18 years or older with anemia due to CKD. The overall quality of evidence was assessed using the GRADE system.

Results

We identified 30 eligible studies including 7843 patients with CKD, and 21/30 studies included patients using hemodialysis or peritoneal dialysis. Compared with ESA biosimilars, epoetin α did not statistically differ for any of the ten measured outcomes. The quality of evidence varied from low to very low. In the comparison between epoetin α vs. darbepoetin α, no differences were observed for all outcomes, but blood transfusions showed favorable results for darbepoetin α: RR 2.18 (1.31–3.62). The quality of evidence varied from low to very low. No differences were observed between epoetin β and methoxy polyethylene glycol-epoetin β, and between darbepoetin α and methoxy polyethylene glycol-epoetin β, the quality of evidence varied from moderate to very low.

Conclusions

Data from 31 included studies allowed to pool data in meta-analysis related to four different comparisons and eleven outcome measures. Nevertheless, only one result was statistically significant in favor of darbepoetin α in the comparison with epoetin α concerning blood transfusions. For all the other outcomes and comparisons, we did not find any differences in terms of efficacy and security between the EPO considered. The quality of evidence is quite low, and further research could change these results. Further high quality studies examining the comparative effectiveness of ESAs need to be conducted.

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Abbreviations

ESA:

Erythropoiesis-stimulating agent

CKD:

Chronic kidney disease

RBC:

Red blood cell

RCT:

Randomized controlled trial

CCT:

Controlled clinical trial

CI:

95% confidence intervals

RR:

Relative risk

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Author contributions

ZM created the search strategy and searched on databases. LA screened, data abstracted, quality appraised and drafted the manuscript. RS secondarily screened, data abstracted and quality appraised. RS assisted with the statistical analysis and editing of the manuscript. All authors conceived of the study, participated in its design and coordination as well as editing of the manuscript. All authors read and approved the final manuscript.

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  1. UOSD Documentazione Scientifica/Scientific Research, Department of Epidemiology, Lazio Regional Health Service, Via Cristoforo Colombo, 112, Scale A-III Plan, 00147, Rome, Italy

    Laura Amato, Antonio Addis, Rosella Saulle, Francesco Trotta, Zuzana Mitrova & Marina Davoli

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  1. Laura Amato
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Correspondence to Rosella Saulle.

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Amato, L., Addis, A., Saulle, R. et al. Comparative efficacy and safety in ESA biosimilars vs. originators in adults with chronic kidney disease: a systematic review and meta-analysis. J Nephrol 31, 321–332 (2018). https://doi.org/10.1007/s40620-017-0419-5

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