Originator Erythropoietin Alpha Vs Biosimilar Erythropoietin Alpha vs Erythropoietin Zed Plus Liposomial Iron and b12 and Folates in Patients with Refractory Anemia. Five Center Retrospective Study
Authors: Giordano Giulio , Mondello Patrizia , Tambaro Rosa , Perrotta Nicola , D'amico Fabio , Berardi Giuseppe , Carabellese Bruno , Equitani Francesco 
Published: October 2019

Abstract
Background
Biosimilar drugs, including erythropoirtin zed, have a similar, but usually not inferior although not hidentical effects of originator drugs. Safety is hidentical to originator drugs.
Aims
Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha and erythropoietin zed, are not inferior to erythropoietin alpha in terms of safety, efficacy and costs.
Methods
This study is a retrospective study.Between july 2008 and december 2013, 101 patients affected by refractory anemia were studied.Median follow-up was 16 months (R10-28). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In group C patient received biosimilar erythropoietin zed 40000 IU sc/weekly. In all three arms patients received liposomial iron (Sideral®) 14 mg 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median age was 70 years (R63-73), M/F: 15/28. In group B median age was 64 years (R60-70), M/F: 24/19. In group C median age was 68 years (R62-73), M/F: 10/5.IPSS was low in 30 patients and int-1 in 12 patients, karyotype showed –Y in two patient, del 20q in one patient, trisomy 8 in two patients in group A. IPSS was low in 32 patients and int-1 in 10 patients, karyotype showed –Y in one patients, del 20q in one patient in group B.IPSS was low in 11 patients and int-1 in 4 patients, karyotype was normal in 9 patients and not evaluable in 6 patients. Patients with 5q- were excluded from this study. Median level of haemoglobin was 9 g/dl in group A (R8-11), 8.7 g/dl (R8.5-10.5) in group B and 8.5 in group C. Cost of every month of erythropoietinic therapy was calculed dividing for each patient the sum of complete erythropoietic therapy for each month of follow-up, then in each group of patients median cost of erythropoietic therapy was calculed.
Results
Group A patients increased Hb level of 1 g/dl after a median time of 5 weeks (R4-9), after a median time of 3.5 weeks (R3-8) in group B and after a memedian time of 4 weeks in group C. No relevant side effects were observed in all three groups groups. Erythropoietin alpha was reduced in group A because Hb achieved a level > 12g/dl after a median of 12 weeks (R 4-18).Biosimilar erythropoietin alpha was reduced in group B because Hb achieved a level > 12g/dl after a median of 10 weeks (R 3-16). Erythropoietin zed was reduced in group C because Hb achieved a level > 12g/dl after a median of 9.5 weeks (R 3-15). In group A maintenance dose was administered with a median of every two weeks (2-4), in group B maintenance dose was administered with a median of every three weeks (2-5), in group C maintenance dose was administered with a median of every three weeks (2-4). Median cost for every month of erythropoietic therapy was 1536 euros/month (R1240-1850) in group A, 1354 euros/month (R954-1550) in group B, 1300 euros/month (R1300-1380) in group C. Five patients need transfusion support in group A,6 patients need transfusion support in group B and 5 in group C.
Summary/Conclusion
Biosimilar erythropoietin alpha and erythropoietin zed plus liposomial iron (Sideral®) and B12 and folates support seems to be safe, feasible, probably equally cost-effective and substantially not inferior to classical erythropoietin alpha support in patients affected by refractory anemia. This study needs confifrmation on a larger cohort of patients.

Disclosures
No relevant conflicts of interest to declare.