Postmarketing adverse event reporting patterns of methoxy polyethylene glycol-epoetin beta: a two-stage disproportionality analysis of FAERS and JADER with active ESA comparators

Abstract Background Methoxy polyethylene glycol-epoetin beta is a long-acting erythropoiesis-stimulating agent (ESA) used for anemia associated with chronic kidney disease. Rare immunogenic events, acute hypersensitivity, and reduced-response reporting patterns require long-term postmarketing assessment. We characterized reporting patterns and time to onset and assessed signal specificity using active ESA comparators and two spontaneous-reporting databases. Methods FDA Adverse Event Reporting System (FAERS) screening for 2018Q1–2026Q1 identified 6,609 reports mentioning the target drug. The primary-suspect comparison yielded 145 preferred terms (PTs) meeting reporting odds ratio and proportional reporting ratio criteria, including 138 three-algorithm consensus signals. In parallel, an exploratory source-restricted rule applied to 402 count-qualified PTs yielded 87 terms, harmonized to 86 Medical Dictionary for Regulatory Activities PTs. These were fixed for lifecycle FAERS and active ESA comparator analyses. Eight events were prioritized post hoc for Japanese Adverse Drug Event Report (JADER) corroboration, time-to-onset analysis, and structured review of public case fields. Results Lifecycle FAERS included 8,965 primary-suspect reports; 38 of 86 and 29 of 86 PTs met consensus versus all other drugs and strict other ESAs, respectively. Haemoglobin decreased and pure red cell aplasia did not meet consensus under active ESA comparison in FAERS. Anaphylactic reaction tended to occur early among reports with evaluable dates; its disproportionality varied by reporting source and period. Among 22 bone marrow failure reports, 16 had competing explanations or event overlap, four had no identified alternative, and two had insufficient information. Among nine ventricular fibrillation reports, seven occurred within acute alternative or event chains and two had insufficient information. Conclusions Comparator choice and reporting context materially changed signal interpretation. The findings support surveillance of known ESA immunogenicity and severe hypersensitivity, but public case fields did not provide positive evidence for target-drug-specific bone marrow failure or ventricular fibrillation. Spontaneous reports cannot estimate incidence or establish causality.