Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies
Rationale & Objective: Epoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
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| Series: | Kidney Medicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590059519300822 |
| _version_ | 1818444538420658176 |
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| author | Jay B. Wish Marcelo G. Rocha Nancy E. Martin Christian Russel D. Reyes Steven Fishbane Mark T. Smith George Nassar |
| author_facet | Jay B. Wish Marcelo G. Rocha Nancy E. Martin Christian Russel D. Reyes Steven Fishbane Mark T. Smith George Nassar |
| author_sort | Jay B. Wish |
| collection | DOAJ |
| description | Rationale & Objective: Epoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-term safety of epoetin alfa-epbx. Study Design: Pooled analyses of previously conducted studies. Setting & Participants: Hemodialysis patients with anemia. Interventions: Data from patients who received 1 or more subcutaneous or intravenous doses of study drug were integrated across route of administration in combined randomized groups (epoetin alfa-epbx, n = 423; epoetin alfa, n = 426). Data from patients who received 1 or more doses of epoetin alfa-epbx in either open-label extension trial were integrated across route of administration in a combined long-term safety studies group (n = 576). Outcomes: Adverse events (AEs), immunogenicity, and other outcomes were assessed. Results: Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were similar between combined randomized epoetin alfa-epbx and epoetin alfa, which had mean treatment durations of 18.1 and 17.7 weeks, respectively. Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were 86.5%, 39.4%, and 6.6%, respectively, for the combined long-term safety studies group, which had a mean treatment duration of 40.0 weeks. In total, 12 patients across the combined randomized groups (epoetin alfa-epbx, n = 5; epoetin alfa, n = 7) and 9 patients in the combined long-term safety studies group tested anti-recombinant human erythropoietin antibody positive in 1 or more visits during study conduct. No patient in any group developed neutralizing antibodies or pure red blood cell aplasia. Limitations: Epoetin alfa comparator not included in the long-term safety studies, greater cumulative exposure to study drug for epoetin alfa-epbx, shorter follow-up in the randomized studies, and potential for selection bias among patients in the open-label long-term safety studies. Conclusions: This analysis reinforces previous conclusions of similar safety profiles between epoetin alfa-epbx and epoetin alfa. Furthermore, epoetin alfa-epbx had no unexpected safety signals during long-term treatment. Funding: This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015. Trial Registration: ClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107). Index Words: Anemia, chronic kidney disease, epoetin alfa-epbx, epoetin alfa, hemodialysis, long-term, safety |
| first_indexed | 2024-12-14T19:17:32Z |
| format | Article |
| id | doaj.art-70749e3d84df4eb6b74e165829bc5d05 |
| institution | Directory Open Access Journal |
| issn | 2590-0595 |
| language | English |
| last_indexed | 2024-12-14T19:17:32Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney Medicine |
| spelling | doaj.art-70749e3d84df4eb6b74e165829bc5d052022-12-21T22:50:31ZengElsevierKidney Medicine2590-05952019-09-0115271280Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label StudiesJay B. Wish0Marcelo G. Rocha1Nancy E. Martin2Christian Russel D. Reyes3Steven Fishbane4Mark T. Smith5George Nassar6Indiana University, Indianapolis, IN; Address for Correspondence: Jay B. Wish, MD, Division of Nephrology, Indiana University Health, 550 North University Blvd, Ste 6100, Indianapolis, IN 46202.Pfizer Inc, Lake Forest, ILPfizer Inc, Lake Forest, ILPfizer Inc, Manila, PhilippinesHofstra Northwell School of Medicine, Hempstead, NYNephrology Associates, Augusta, GAHouston Methodist Hospital, Houston, TXRationale & Objective: Epoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-term safety of epoetin alfa-epbx. Study Design: Pooled analyses of previously conducted studies. Setting & Participants: Hemodialysis patients with anemia. Interventions: Data from patients who received 1 or more subcutaneous or intravenous doses of study drug were integrated across route of administration in combined randomized groups (epoetin alfa-epbx, n = 423; epoetin alfa, n = 426). Data from patients who received 1 or more doses of epoetin alfa-epbx in either open-label extension trial were integrated across route of administration in a combined long-term safety studies group (n = 576). Outcomes: Adverse events (AEs), immunogenicity, and other outcomes were assessed. Results: Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were similar between combined randomized epoetin alfa-epbx and epoetin alfa, which had mean treatment durations of 18.1 and 17.7 weeks, respectively. Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were 86.5%, 39.4%, and 6.6%, respectively, for the combined long-term safety studies group, which had a mean treatment duration of 40.0 weeks. In total, 12 patients across the combined randomized groups (epoetin alfa-epbx, n = 5; epoetin alfa, n = 7) and 9 patients in the combined long-term safety studies group tested anti-recombinant human erythropoietin antibody positive in 1 or more visits during study conduct. No patient in any group developed neutralizing antibodies or pure red blood cell aplasia. Limitations: Epoetin alfa comparator not included in the long-term safety studies, greater cumulative exposure to study drug for epoetin alfa-epbx, shorter follow-up in the randomized studies, and potential for selection bias among patients in the open-label long-term safety studies. Conclusions: This analysis reinforces previous conclusions of similar safety profiles between epoetin alfa-epbx and epoetin alfa. Furthermore, epoetin alfa-epbx had no unexpected safety signals during long-term treatment. Funding: This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015. Trial Registration: ClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107). Index Words: Anemia, chronic kidney disease, epoetin alfa-epbx, epoetin alfa, hemodialysis, long-term, safetyhttp://www.sciencedirect.com/science/article/pii/S2590059519300822 |
| spellingShingle | Jay B. Wish Marcelo G. Rocha Nancy E. Martin Christian Russel D. Reyes Steven Fishbane Mark T. Smith George Nassar Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies Kidney Medicine |
| title | Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies |
| title_full | Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies |
| title_fullStr | Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies |
| title_full_unstemmed | Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies |
| title_short | Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies |
| title_sort | long term safety of epoetin alfa epbx for the treatment of anemia in eskd pooled analyses of randomized and open label studies |
| url | http://www.sciencedirect.com/science/article/pii/S2590059519300822 |
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