RESUMO
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).
RESUMO
BACKGROUND: Hydroxypropyl-ß-cyclodextrin-diclofenac (HPßCD-diclofenac) is an NSAID used to treat acute moderate-to-severe postoperative pain. This post hoc analysis investigated the safety of HPßCD-diclofenac in patients aged ≥ 65 years. METHODS: Data from three phase III trials of HPßCD-diclofenac in adult patients with acute moderate-to-severe postoperative pain were pooled (NCT00448110, NCT00507026, and NCT00726388). Patients who received one or more dose of HPßCD-diclofenac or placebo were included and stratified according to age: < 65, 65-74, or ≥ 75 years. Numerical and categorical variables were compared across the groups using ANOVA and Cochran-Mantel-Haenszel tests, respectively. Cochran-Mantel-Haenszel relative risks compared with placebo were calculated, adjusted by study. RESULTS: Overall, 1289 patients were included: 878, 282, and 129 in the < 65, 65-74, and ≥ 75-years groups, respectively. Overall incidence of treatment-emergent adverse events (TEAEs) was similar in the three groups (p = 0.4360). Incidences of postoperative anemia (p < 0.0001), constipation (p = 0.0017), and hypotension (p = 0.0003) increased significantly across the age groups, whereas headache (p = 0.0008) and flatulence (p = 0.0118) decreased significantly. Relative risks for all System Organ Class categories and preferred terms investigated were similar among the groups and similar to placebo. CONCLUSIONS: Overall incidence of TEAEs in patients aged 65-74 or ≥ 75 years was similar to patients aged < 65 years. The groups displayed similar relative risks for the most frequent TEAEs, which were all similar to placebo. The TEAE profiles of the groups showed differences, all of which may be anticipated due to age-related differences in susceptibility and the types of surgery most commonly performed in each group. CLINICALTRIALS. GOV IDENTIFIERS: NCT00448110, NCT00507026, and NCT00726388.