Evaluation of the post-marketing safety of eculizumab from 2007 to 2025: A real-world pharmacovigilance study and signal analysis based on the FAERS database.

OBJECTIVE: Eculizumab is a terminal complement C5 inhibitor widely used in the treatment of various complement-mediated diseases. Its safety information primarily comes from clinical trials and FDA labeling. This study aimed to systematically assess the real-world safety profile of Eculizumab based on the FDA Adverse Event Reporting System (FAERS) and to identify new adverse drug reactions (ADRs) that are not sufficiently highlighted in the product label.

METHODS: Adverse event reports related to Eculizumab from the FAERS database (2007 Q1-2025 Q2) were retrieved. Signal detection was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The occurrence time and subgroup differences across populations were analyzed.

RESULTS: A total of 158,246 adverse event reports were included, of which 50,671 involved Eculizumab as the primary suspected drug, spanning 27 System Organ Classes (SOCs). The most commonly reported events were systemic reactions (17.3 %), abnormal findings on examination (14.4 %), and infections (9.2 %). Known major adverse reactions, such as headache, fatigue, and nasopharyngitis, as well as critical warnings like Neisseria meningitidis infections, were validated in this study. Additionally, new high-signal ADRs, not sufficiently addressed or included in the label, were identified, such as extravascular hemolysis (ROR = 513.45 [412.63-638.9]), disseminated gonococcal infection (ROR = 260.92 [90.5-752.02]), and Waterhouse-Friderichsen syndrome (ROR = 160.57 [61.03-422.46]). Urinary tract infections were significantly increased in females and elderly patients (ROR =1.98 [1.81-2.16]). The median time to adverse event occurrence was 252 days (IQR 36-828 days), with approximately 25 % of events occurring within 36 days. While the overall risk by gender was similar, the distribution of event types differed; patients under 18 years had the highest cumulative incidence and showed unique signals like thrombotic microangiopathy. Patients aged 65 and older had higher reports of falls and urinary tract infections. Reports from healthcare professionals appeared earlier and were more frequent.

CONCLUSION: In the real-world setting, Eculizumab, in addition to its known hematological and infection risks, is associated with several rare but highly relevant new ADR signals, including severe hematological abnormalities, specific infections, renal damage, falls, and reproductive-related events. Clinical strategies for layered monitoring should be developed for different populations, and this evidence should support updates to the product label.